Background

In the pivotal OAK study (NCT02008227), atezo (anti–PD-L1) significantly improved OS vs docetaxel in previously treated NSCLC. The phase III/IV TAIL study (NCT03285763) evaluated the safety and efficacy of atezo in pts with previously treated advanced NSCLC, including those generally excluded from key clinical trials. At the primary analysis, the co-primary endpoints, treatment-related (TR) serious adverse events (SAEs) and TR immune-related adverse events (irAEs), occurred in 7.8% and 8.3% of pts, respectively. No new safety signals were seen. Here we report final safety and efficacy data from TAIL.

Methods

Pts with advanced NSCLC who progressed after 1-2 lines of chemotherapy were enrolled. Pts received 1200 mg of atezo IV once every 3 weeks. Coprimary endpoints were TR SAEs and TR irAEs. Key secondary endpoints included OS, PFS, ORR and DOR. Safety and efficacy in key pt subgroups were also assessed.

Results

Of 619 enrolled pts, 615 received atezo. Median age was 64 y, 60% of pts were male and 90% had ECOG PS 0/1. At data cutoff (26 June 2021), median follow-up was 36.1 mo (range, 0.0-42.3) and 473 pts (77%) had died. TR SAEs and TR irAEs (95% CI) occurred in 8.0% (6, 10) and 9.4% (7, 12) of pts, respectively. The most common Grade ≥3 TR SAEs were pneumonitis (1.0%; including 1 Grade 5 event), pericarditis and colitis (both 0.5%). Safety data for the subgroups were similar to those for the overall population; despite a moderately higher incidence of TR SAEs in the ECOG PS 2 subgroup (13.1%; n=8/61) vs the overall population, the incidence of irAEs was similar (8.2%). Efficacy data are shown in the table.

Conclusions

With a median follow-up of ≈3 y, no new or unexpected safety signals were seen. These updated data confirm a positive risk-benefit ratio for atezo in the prior-treated NSCLC setting and may prove useful for informing tx decisions in pts generally excluded from pivotal NSCLC trials. Table: 9P

Clinical trial identification

NCT03285763.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Derrick Afful, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

A. Ardizzoni: Financial Interests, Personal, Advisory Board: Eli Lilly, Bristol Myers Squibb, MSD, Roche, Astra Zeneca, Takeda, Bayer. B. Rubio-Viqueira: Financial Interests, Personal, Invited Speaker: MSD, Bristol; Financial Interests, Personal, Advisory Board: MSD, Lilly, Takeda. D. Rodriguez-Abreu: Financial Interests, Personal, Other, Personal Fees and other: Bristol Myers Squibb, MSD, Roche/Genentech, Novartis, Astra Zeneca, Boehringer. J. Alatorre-Alexander: Financial Interests, Personal, Advisory Board: Astra Zeneca, Roche, MSD, Bristol Myers Squibb, Takeda, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Bristol Myers Squibb, Takeda, Pfizer. H.J.M. Smit: Financial Interests, Personal, Advisory Board: MSD, Bristol Myers Squibb, AstraZeneca; Financial Interests, Institutional, Principal Investigator: MSD, Bristol Myers Squibb, AstraZeneca, Beigene, Roche. E. Hoglander: Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Full or part-time Employment: Roche. M. Kaul: Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Full or part-time Employment: Genentech. J. Tolson, Y. Hu: Financial Interests, Personal, Full or part-time Employment: Roche. H.K. Vollan: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. T. Newsom-Davis: Financial Interests, Personal, Advisory Board: Amgen, Bayer, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, MSD, Novartis, Otsuka, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Guardant, MSD, Takeda, Roche; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli Lilly, MSD, Otsuka, Roche, Takeda. All other authors have declared no conflicts of interest.

Background

TFS is an emerging clinical endpoint that measures the time between treatment (Tx) cessation and subsequent Tx initiation or death. This framework divides restricted mean (r-mean) overall survival (OS) into periods on and off Tx, with/without toxicity. In CM227, mNSCLC pts received 1L Tx with either NIVO+IPI up to a maximum of 2 years or PDC, up to four cycles with optional maintenance for non-squamous pts.

Methods

Data were analyzed for pts randomized to NIVO+IPI (n=583) or PDC (n=583) in CM227. OS was estimated by Kaplan-Meier (KM) method. TFS was defined as the area between KM curves for 2 time-to-event endpoints defined from randomization: time to protocol Tx cessation and time to subsequent Tx/death. TFS was also divided into TFS with/without ongoing grade (gr) ≥3 treatment-related adverse events (TRAEs). The area under the KM curves was estimated by the 4-year r-mean time and expressed as a percentage of this period.

Results

Over 4 years, pts’ r-mean OS was 23.27 and 19.06 months and r-mean time on protocol therapy was 8.31 and 5.6 months for NIVO+IPI and PDC, respectively (Table). Pts spent 18.1% vs 9.1% of the 4-year period in TFS with NIVO+IPI and PDC, respectively (r-mean TFS, 8.70 and 4.38 months). NIVO+IPI pts had r-mean TFS that was 4.32 months longer than PDC pts (95% CI, 2.47, 6.16). Mean TFS with gr ≥3 TRAEs was a small proportion of the 4- year period, 0.9%, and 0.3% with NIVO+IPI and PDC, respectively. Table: 10P

Estimated r-mean (months) OS and TFS over 4 years

Conclusions

In this CM227 analysis, NIVO+IPI conferred longer r-mean TFS with/without toxicity compared to PDC, doubling the proportion of the 4-year period in TFS. The majority of TFS time in both arms was spent without gr ≥3 TRAEs.

Clinical trial identification

NCT02477826.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Fishawack, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, OncologyEducation, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Talk in a company's organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda, Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, GlaxoSmithKline, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics, Roche/Genentech. J. Penrod: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb. J. Li, S. Lubinga, R. Gupta: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Rizzo: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Patent Filing: Bristol Myers Squibb. S. Ramalingam: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Advaxis; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Takeda; Financial Interests, Institutional, Sponsor/Funding: Genmab.

Background

Eftilagimod alpha (efti) is a soluble LAG-3 protein binding to a subset of MHC class II molecules to mediate antigen presenting cell (APC) and CD8 T-cell activation. Stimulating APCs and subsequent T cell recruitment with efti may revert PD-1 resistance. We hereby report results from part B, 2^nd line PD-1/PD-L1 refractory non-small cell lung carcinoma (NSCLC), of the TACTI-002 trial.

Methods

Patients (pts) with previously treated metastatic NSCLC, refractory to PD-1/PD-L1 and unselected for PD-L1 expression were enrolled. A Simon's 2-stage design was used, with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include ORR by RECIST 1.1, tolerability, disease control rate (DCR), progression free survival and overall survival. Pts received 30 mg efti (SC) q2w for 8 cycles (1 cycle= 3 wks) and then q3w for up to one year together with pembrolizumab (200 mg IV q3w for up to 2 years). Imaging was performed every 8 weeks and evaluated locally. The study was approved by relevant authorities and ethics committees.

Results

36 pts were enrolled in this cohort. Median age was 66 years (50-84) and 61 % were male. The ECOG PS was 0 and 1 in 33 % and 67 % of pts, respectively. Pts had squamous (19 %) and non-squamous (78 %) NSCLC. Pts were pretreated with a PD-1/ PD-L1 antagonist alone (33 %) or in combination with platinum-based chemo (67 %). All PD-L1 subgroups were included with 36 % being PD-L1 negative. Pts received a median 4.0 (range 1–18) pembrolizumab and 5.0 (range 1-22) efti administrations. 2 pts discontinued treatment due to adverse reactions (ARs) (5.6 %). The most common (>15 %) AEs were decreased appetite (33 %), dyspnea (31 %), cough (25 %), asthenia (22 %), fatigue (17 %) and weight decreased (17 %). At data cut-off (Nov2021) 36 pts were evaluated for response with a min. follow-up of ≥4 months. ORR (iRECIST) and DCR was 6 % (2/36) and 36 % (13/36), respectively. Both responses were reported in pts pre-treated with chemo + PD-1 and under therapy since 7+ and 12+ months at data cut-off.

Conclusions

Efti in combination with pembrolizumab is safe and shows encouraging signs of antitumor activity in PD-1 refractory 2^nd line NSCLC pts.

Clinical trial identification

EudraCT 2018-001994-25; NCT03625323.

Legal entity responsible for the study

Immutep S.A.

Funding

Immutep S.A.

Disclosure

M.G. Krebs: Other, Personal, Speaker’s Bureau: Roche, Janssen, AstraZeneca; Other, Institutional, Funding: Roche (Inst); Other, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; BerGenBio; Immutep; Other, Personal, Other, Consulting or Advisory Role: Janssen; Roche, Bayer, Seattle Genetics; Other, Personal, Other, Honoraria: Roche, Janssen. M. Majem Tarruella: Other, Personal, Other, Consulting or Advisory Role: AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb;Helsinn Therapeutics; Lilly; MSD; Novartis; Pfizer; Roche; Takeda; Tesaro; Other, Institutional, Funding: Bristol Myers Squibb(Inst); Other, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Roche. M. Forster: Other, Personal, Other, Consulting or Advisory Role : Achilles Therapeutics; AstraZeneca; Bayer; Bristol Myers Squibb; Celgene; Guardant Health; Lilly; MSD; Nanobiotix; Novartis; Oxford VacMedix; Pfizer; PharmaMar; Roche; Takeda; Other, Institutional, Funding: AstraZeneca (Inst); Boehringer Ingelheim (Inst); Merck Serono (Inst); MSD Oncology (Inst); Other, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Bristol Myers Squibb; Celgene; Guardant Health; MSD Oncology; Roche. J.A. Peguero: Other, Personal, Other, Employment: Oncology Consultants, P.A.; Other, Personal, Leadership Role: Director, Research Department. T. Clay: Other, Personal, Other, Honoraria : AstraZeneca; Novartis; Roche; Other, Personal, Speaker’s Bureau: AstraZeneca; Novartis; Novartis; Other, Institutional, Funding: Bayer (Inst); Bayer (Inst); BeyondSpring Pharmaceuticals (Inst); Clovis Oncology (Inst); Exelixis (Inst); Immutep (Inst); MSD (Inst); Other, Personal, Other, Travel, Accommodations, Expenses : Astellas Pharma; Astra Zeneca; Bristol Myers Squibb; Foundation Medicine; Roche/Genentech. E. Felip: Other, Personal, Other, Advisory Board and Invited Speaker : Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, MSD, Merck Serono, Pfizer; Other, Personal, Advisory Board: Bayer, BeiGene, Boehringer Ingelheim, GlaxsoSmithKline, Medical Trends, Peptomyc, Puma Biotechnology, Regeneron, Sanofi, Takeda; Other, Personal, Invited Speaker: PeerVoice, Springer, Touch Medical; Other, Institutional, Funding: Grant for Oncology Innovation, Merck Healthcare KGaA, Fundación Merck Salud; Other, Personal, Other, Independent Member of the Board: GRÍFOLS. W. Iams: Other, Personal, Advisory Board: Genentech, Jazz Pharma, G1 Therapeutics, Mirati, Bristol Myers Squibb, Takeda, Janessen; Other, Personal, Other, Consultant: OncLive, Clinical Care Options, Chardan, Outcomes Insights, Cello Health, Curio Science. P. Roxburgh: Other, Institutional, Funding: AstraZeneca, Tesaro/GlaxoSmithKline, Atrios; Other, Personal, Other, Honoraria: AstraZeneca, Tesaro/GlaxoSmithKline; Other, Institutional, Funding, Funding to institution for role as site PI: Sierra Oncology, PsiOxus, AstraZeneca, Starpharma, Forma Therapeutics, Iovance, Immutep, Bayer, Athenex, Replimune, Clovis, Nucana. C. Mueller: Financial Interests, Personal, Other, Employment: Immutep. F. Triebel: Financial Interests, Personal, Other, Employment: Immutep SAS; Financial Interests, Personal, Stocks/Shares: Immutep Ltd; Non-Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: Being an inventor on patents on LAG-3 owned by Immutep SAS. All other authors have declared no conflicts of interest.

Background

Acquired resistance to EGFR TKI remains a significant barrier for patients with EGFR-mutated lung cancer, especially for those without acquired EGFR^T790M. The current study explored the safety and efficacy of combinational treatment with atezolizumab, bevacizumab, and pemetrexed-platinum in patients with EGFR-mutated NSCLC after failure of EGFR TKIs.

Methods

NSCLC patients with activated EGFR mutations after failure of EGFR TKIs were recruited, and patients with T790M were excluded. The treatment is to combine atezolizumab, bevacizumab (7.5 mg/kg), and pemetrexed-platinum once every 3 weeks until progression. Endpoints were ORR, PFS, and OS. For comparison, we retrieved a historical control group that enrolled patients with EGFR mutations who received pemetrexed-platinum plus bevacizumab after failure of single using EGFR TKI from 2009 to 2020. This study is active and recruiting patients is still ongoing.

Results

Twenty patients were enrolled, and the median age was 62 years. Seven patients had taken osimertinib before enrollment. PD-L1 expression was ≧ 1% in 35.0%. The median follow-up time was 15.6 months. One patient was excluded from response analysis due to idiopathic thrombocytopenic purpura being diagnosed after 1st-cycle treatment. ORR was 42.1%, and the DCR was 100%. Median PFS was 10.2 months, and OS was not mature yet. Patients with PD-L1 ≧ 1% have a higher ORR than those with PD-L1 < 1% (85.7% vs. 16.7%; p = 0.003). Compared with the historical control group (Bev/Pem/Platin) (n = 53), the experimental treatment (Atezo/Bev/Pem/Platin) showed significant benefits in DCR (100.0% vs. 64.2%; p = 0.002) and PFS (10.2 vs. 5.9 mo.; p = 0.007). There were no significant differences in ORR (42.1% vs. 30.2%; p = 0.401) and OS (unmatured vs. 19.3 mo.; p = 0.134). Grade ≧ 3 adverse events occurred in 40.0% (8/20) patients, especially 2 venous thromboembolism, 1 hydrocephalus, and 1 renal abscess.

Conclusions

The combination treatment of atezolizumab, bevacizumab, and pemetrexed-platinum provided favorable efficacy in EGFR-mutated NSCLC after TKI failure. The DCR and PFS of pemetrexed-platinum plus bevacizumab could be improved by the addition of atezolizumab.

Clinical trial identification

NCT 04147351.

Legal entity responsible for the study

The authors.

Funding

Roche.

Disclosure

S. Wu: Financial Interests, Personal, Invited Speaker, speaking honoraria: Roche; Financial Interests, Personal, Invited Speaker, speaking honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker, speaking honoraria: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, speaking honoraria: Novartis; Financial Interests, Personal, Invited Speaker, speaking honoraria: Eli Lilly; Financial Interests, Personal, Invited Speaker, speaking honoraria: MSD; Financial Interests, Personal, Invited Speaker, speaking honoraria: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, speaking honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, travel expense: Roche; Financial Interests, Personal, Other, travel expense: Boehringer Ingelheim. C. Ho: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Roche-Genentech; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceuticals; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Ono Pharmaceuticals. J.C. Yang: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Invited Speaker: Clovis Oncology; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Bayer. B. Liao: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. Y. Lin: Financial Interests, Personal, Invited Speaker: ACT Genomics; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Manudipharma; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: TTY Biopharm; Financial Interests, Personal, Other, travel expense: Pfizer. W. Liao: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Speaker’s Bureau: MSD Oncology; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai Pharma Taiwan; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma Taiwan. J. Shih: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Other, travel expense: Roche; Financial Interests, Personal, Other, travel expense: Pfizer; Financial Interests, Personal, Other, travel expense: MSD; Financial Interests, Personal, Other, travel expense: Chugai Pharmaceutical; Financial Interests, Personal, Other, travel expense: Bristol Myers Squibb. All other authors have declared no conflicts of interest.

Background

Osimertinib is third generation, irreversible, CNS-active EGFR-TKI, and preferred 1L treatment in pts with advanced EGFRm NSCLC. Pts on 1L osimertinib may develop treatment resistance and experience disease progression. The ongoing phase II, open-label, biomarker-directed platform study ORCHARD (NCT03944772) aims to characterise resistance mechanisms and evaluate novel therapy combinations in pts who progressed on 1L osimertinib. This interim analysis reports results of durvalumab + chemotherapy in pts with no biomarker-detected resistance mechanisms or for whom biomarker-directed study treatments were not available.

Methods

Adults (WHO PS 0–1) with EGFRm NSCLC who did not harbour a pre-specified alteration by next-generation sequencing on post-TKI biopsy, received durvalumab (1500 mg; intravenous, IV) + carboplatin (target area under the curve 5; IV) + pemetrexed (500 mg/m² body surface area; IV) on Day 1 of 21-day cycles for 4–6 cycles, followed by durvalumab + pemetrexed maintenance treatment on Day 1 of 28-day cycles, thereafter. Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Data cut-off (DCO): 25 June 2021.

Results

Twenty-five pts (median age, 61 yrs; female, n=19 [76%]; CNS metastases, n=6 [24%]) were enrolled. All pts received ≥75% relative dose intensity for all study drugs; 22 pts (88%) discontinued all treatments by DCO. ORR was 12% (n=3/25; confidence intervals, CI: 4, 25; confirmed partial responses). Stable disease was reported in 17/25 pts (68%; including six unconfirmed partial responses [24%]) and progressive disease in 4/25 (16%) pts. One (4%) pt was non-evaluable. Median PFS was 4.8 months (95% CI: 2.6, 7.6). Recruitment was paused as stop criteria (≤10% chance ORR is ≥45%) were met. Treatment-related serious adverse events occurred in two pts (8%); there were no interstitial lung disease events.

Conclusions

In this pt population, durvalumab + chemotherapy treatment was well tolerated with no new safety signals; however, stop criteria were met with this combination, and recruitment was closed.

Clinical trial identification

NCT03944772.

Editorial acknowledgement

Leon Newman, PhD, of Ashfield MedComms, provided medical writing support that was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc; Financial Interests, Personal, Advisory Board: Brigebio therapeutics; Financial Interests, Personal, Advisory Board: Cyrus therapeutics; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Joseah BIO; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp; Financial Interests, Personal, Ownership Interest: DAAN Biotherapeutics; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc; Financial Interests, Personal, Stocks/Shares: Gencurix Inc; Financial Interests, Personal, Stocks/Shares: Bridgebio therapeutics; Financial Interests, Personal, Stocks/Shares: KANAPH Therapeutic Inc; Financial Interests, Personal, Stocks/Shares: Cyrus therapeutics; Financial Interests, Personal, Stocks/Shares: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: MOGAM Institute; Financial Interests, Personal, Research Grant: Dong-A ST; Financial Interests, Personal, Research Grant: Champions Oncology; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Yuhan; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Research Grant: Dizal Pharma; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Medpacto; Financial Interests, Personal, Research Grant: Gllnnovation; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Blueprint medicines; Financial Interests, Personal, Research Grant: Interpark Bio Convergence Corp.; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Boehringer-Ingelheim, Roche; Financial Interests, Personal, Other, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Other, consulting fees: Ono; Financial Interests, Personal, Other, consulting fees: Yuhan; Financial Interests, Personal, Other, consulting fees: Pfizer; Financial Interests, Personal, Other, consulting fees: Eli Lilly; Financial Interests, Personal, Other, consulting fees: Janssen; Financial Interests, Personal, Other, consulting fees: Takeda; Financial Interests, Personal, Other, consulting fees: MSD; Financial Interests, Personal, Other, consulting fees: Medpacto; Financial Interests, Personal, Other, consulting fees: Blueprint medicines. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Alpha Pharmaceutical. C. Baik: Financial Interests, Personal, Advisory Board: BluePrint; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: TurningPoint; Financial Interests, Personal, Advisory Board: Guardant; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Silverback; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Spectrum; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: TurningPoint. R. García: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: BI; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: BI; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Janssen; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: Takeda; Non-Financial Interests, Personal, Principal Investigator: Lilly; Non-Financial Interests, Personal, Principal Investigator: Novartis; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: BI; Non-Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Janssen; Non-Financial Interests, Personal, Principal Investigator: Verastem; Non-Financial Interests, Personal, Principal Investigator: Amgen; Non-Financial Interests, Personal, Advisory Role: MSD; Non-Financial Interests, Personal, Advisory Role: Roche; Non-Financial Interests, Personal, Advisory Role: Takeda; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: BI; Non-Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Janssen. J.W. Goldman: Financial Interests, Personal, Research Grant: Advaxis; Financial Interests, Personal, Research Grant: Array; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Genentech/Roche; Financial Interests, Personal, Research Grant: G1 Therapeutics; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoria: AstraZeneca; Financial Interests, Personal, Other, Honoria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoria: Genentech; Financial Interests, Personal, Other, Honoria: Pfizer. S. Kim: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Eli Lilly & Co; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other: Boehringer-Ingelheim. M. Nishio: Financial Interests, Personal, Advisory Role, Consultancy fees, honoraria: Lilly; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Personal, Advisory Role, Consultancy fees, honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy fees, honoraria: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Advisory Role, consulting/advisory: AbbVie; Financial Interests, Personal, Advisory Role, consulting/advisory: Takeda; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Personal, Other, honoraria: Takeda; Financial Interests, Personal, Other, honoraria: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Honoraria: Nippon Kayaku; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Advisory Role, consulting/advisory: Teijin Pharma. R. Salgia: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Advisory Board: Janssen. S. Teraoka: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Pfizer Inc. T. Yoshida: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: ONO Pharmaceutical; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: ONO Pharmaceutical; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Chugai Pharmaceutical; Financial Interests, Personal, Principal Investigator: ONO Pharmaceutical. H.A. Yu: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Cullinan; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: BluePrint Medicine; Financial Interests, Personal, Other, Honoraria: C4 Therapeutics; Financial Interests, Personal, Other, Honoraria: Daiichi. H. Ambrose: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Cosaert: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Project Lead, Lead MD on AZ-sponsored trials: AstraZeneca; Financial Interests, Personal, Leadership Role, Lead MD on AZ-sponsored trials: AstraZeneca. R. Hartmaier: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Maidment: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Pluta: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Okamoto: Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Research Grant: MSD Oncology; Financial Interests, Personal, Research Grant: Astellas Pharma; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Chugai Pharma; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: Pfizer. All other authors have declared no conflicts of interest.

Background

NIVO is approved in China as 2L tx for advanced NSCLC via weight-based 60-minute (min) infusion. We further investigated the safety and efficacy of the more convenient flat dosing via a 30-min infusion in pts with advanced NSCLC, including those with hepatis B virus (HBV) due to its prevalence in China.

Methods

Asian (mostly Chinese) pts with previously treated advanced NSCLC received NIVO 240 mg over 30 min every 2 weeks (Q2W) for up to 2 years (y). High-grade (G3–5) select tx-related adverse events (sTRAE) were analysed by HBV infection status (primary endpoint). Secondary and exploratory endpoints included efficacy and patient-reported outcomes (PROs) among pt subgroups.

Results

Overall, 400 pts were treated: 383 non-HBV infected; 34 EGFR positive (+); 168 and 174 had PD-L1 ≥1% and <1%, respectively. Median (med) age was 61 y. Most pts were male (78.5%), had non-squamous histology (65.8%), and stage IV (77.3%) disease. Minimum follow-up (f/u) was 35.4 months (mo) and med tx duration was 3.24 mo. At a med f/u of 37.6 mo, occurrence of G3–4 sTRAE was low regardless of HBV status. No G5 sTRAEs were reported. Med overall survival was 14.2 (12.3–18.1) and 22.3 (10.0–NA) mo for non-HBV and HBV-infected, 19.3 (11.2–31.7) and 13.7 (11.5–18.1) mo for EGFR+ and negative, and 19.3 (12.9–23.5) and 13.3 (10.9–17.7) mo for PD-L1 ≥1% and <1% subgroups. No notable changes from baseline were observed in PROs among those subgroups. Table: 14P

Conclusions

NIVO 240 mg 30-min infusion Q2W was well-tolerated in Asian pts with previously treated advanced NSCLC, regardless of HBV, EGFR and PD-L1 status. Results were consistent with CheckMate 078 study. Data should be interpreted with caution given the small subgroup sample size.

Clinical trial identification

Protocol CA209870.

Editorial acknowledgement

Medical writing assistance was provided by Alice Carruthers BSc (Hons), PhD, and Julia Ventura BScBiotech, MSc, of Nucleus Global, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb Company.

Funding

Bristol Myers Squibb.

Disclosure

S. Lu: Financial Interests, Personal and Institutional, Sponsor/Funding, Lu S disclosed the Grants from AstraZeneca, Hutchison, Bristol Myers Squibb, Heng Rui Beigene and Roche, Hansoh, and Consulting fee from AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, Yuhan Corporation, PrIME Oncology, Menarini, InventisBio Co. Ltd., and Roche, and Payment or honoraria from AstraZeneca, Roche, Hansoh, Hengrui Therapeutics, and Advisory Board for Roche, Regenron, AstraZeneca, Xcovery Holding, and leadership or fiduciary role in Chinese Lung Cancer Associate, CSCO.: Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University. Y. Cheng: Financial Interests, Institutional, Sponsor/Funding: Jilin Cancer Hospital. J. Zhou: Financial Interests, Institutional, Sponsor/Funding: First Affi liated Hospital, College of Medicine, Zhejiang University. M. Wang: Financial Interests, Institutional, Sponsor/Funding: Peking Union Medical College Hospital. J. Zhao: Financial Interests, Institutional, Sponsor/Funding: Beijing Cancer Hospital. B. Wang: Financial Interests, Institutional, Sponsor/Funding: Jinan Military General Hospital. G. Chen: Financial Interests, Institutional, Sponsor/Funding: Affiliated Cancer Hospital of Harbin Medical University. J. Feng: Financial Interests, Institutional, Sponsor/Funding: Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital. Z. Ma: Financial Interests, Institutional, Sponsor/Funding: Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital,. L. Wu: Financial Interests, Institutional, Sponsor/Funding: Hunan Cancer Hospital (The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University). C. Wang: Financial Interests, Institutional, Sponsor/Funding: Tianjin Medical University Cancer Institute & Hospital. K. Ma: Financial Interests, Institutional, Sponsor/Funding: The First Hospital of Jilin University. S. Zhang: Financial Interests, Institutional, Sponsor/Funding: Beijing Chest Hospital. J. Liang: Financial Interests, Institutional, Sponsor/Funding: Peking University International Hospital. Y. Song: Financial Interests, Institutional, Sponsor/Funding: Nanjing General Hospital. J. Wang: Financial Interests, Institutional, Sponsor/Funding: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences. Y. Wu: Financial Interests, Personal and Institutional, Invited Speaker, Wu YL disclosed personal fees from Honorarium received from AstraZeneca, Beigen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, MSD, Pfizer, Roche, Sanofi, grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, outside the submitted work. : Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences. A. Li: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Bristol Myers Squibb Company. Y. Huang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Chang: Financial Interests, Institutional, Sponsor/Funding: Shanghai Cancer Center Fudan University.

Background

Histone deacetylase inhibitor tucidinostat (formerly known as chidamide) combined with PD-1 inhibitor displays promising activity in hematologic tumors. For non-small cell lung cancer (NSCLC) with driver mutations failed to standard therapies, exploratory immune-based regimens are needed. This phase 1b study assessed safety and preliminary efficacy of tucidinostat with sintilimab in refractory NSCLC patients.

Methods

NSCLC patients with oncogenic alterations relapsed on standard targeted therapies or chemotherapy were enrolled and administered with tucidinostat 20mg, 30mg, or 40mg twice per week and sintilimab 200mg in a three-week cycle, until disease progression or unacceptable toxicity. Safety was evaluated by CTCAE v5.0, and efficacy was assessed by iRECIST.

Results

Between August 25, 2021 and November 30, 2021, twelve eligible patients were enrolled. Two dose limited toxicity events were recorded in the 40 mg cohort, including grade 3 fever and nausea in the first cycle. Grade 1/2 adverse events were observed in all patients, including fatigue (58.3%), anorexia (41.7%), leucopenia (33.3%), neutropenia (25.0%), anemia (25.0%), vomiting (16.7%), erythra (16.7%), nausea (25.0%) and thrombocytopenia (16.7%), with no grade 3/4 hematologic toxicities. Until the cutoff time January 10, 2022, the objective response rate was 8.3%, disease control rate was 58.3%, and median progression-free survival has not reached, with a median follow-up time of 2.3 (range, 1.4-4.6) months. The follow-up remains ongoing and updated results will be presented at the meeting. Table: 15P

Conclusions

Tucidinostat combined with sintilimab showed generally acceptable safety and preliminary activity in refractory NSCLC. Recommended dose of tucidinostat in NSCLC was established at 30 mg, and the phase 2 trial is ongoing.

Clinical trial identification

ChiCTR2000034888 (November 2, 2020).

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

As a rare and highly aggressive malignancy, pulmonary sarcomatoid carcinoma (PSC) is insensitive to chemotherapy or radiotherapy and no optimal treatment has been established yet. Because of the high expression of programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs) were documented to possess encouraging efficacy in PSC patients (pts). Here we evaluated camrelizumab (Camre) in treating PD-1-positive PSC. Apatinib (Apa) may be used simultaneously with Camre based on the PD-L1 level, as the combination of Camre and Apa exhibited treatment potential in lung cancer in previous study.

Methods

In this single-arm, open-label, multicenter, phase II study, pts with an age of 18-80 years old, ECOG PS 0-2, PD-L1 positive, histologically or cytologically confirmed stage IIIB-IV PSC regardless of prior therapy lines were enrolled to receive Camre (200 mg, IV, Q3W) plus Apa (250mg, QD) for PD-L1 TPS 1-49%, or Camre monotherapy (200 mg IV Q3W) for PD-L1 TPS≥50%. The primary endpoint was ORR according to RECIST v1.1.

Results

From Sep 2020 to Nov 2021, 16 pts (Camre plus Apa, n=3; Camre monotherapy, n=13) were enrolled. Until the final follow-up (Nov 30, 2020), 14 pts received at least one efficacy evaluation. In Camre plus Apa group, ORR was 66.7% (2/3), DCR was 66.7% (2/3), median DoR was 2.53 [95% CI 1.4-3.1] months. In Camre monotherapy group, ORR was 54.5% (6/11), DCR was 90.9% (10/11), median DOR was 3.19 [95% CI 1.1-6.9] months. Median PFS and OS data were not mature. Grade 3 or 4 adverse events were AST/ALT increased [1 (6.25%)], hypophysitis [1 (6.25%)], with no unexpected adverse effects. Adverse events that led to the discontinuation of any agent occurred in 1.9% (3/16) of the pts. No treatment-related deaths were reported.

Conclusions

Camre monotherapy or plus Apa showed promising antitumour activity with manageable toxicity profile for PD-L1-positive PSC pts. This encourages the clinical practice with ICIs in PSC.

Clinical trial identification

ChiCTR2000032649, China.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Sint has shown efficacy in randomized, double-blind, phase 3 studies in Chinese patients with NSCLC in ORIENT 11 and ORIENT 12. To further address the safety profile of sint, we present pooled safety and tolerability data from both studies.

Methods

ORIENT 11 enrolled (2:1) patients with advanced/metastatic nonsquamous NSCLC to receive either sint 200 mg or placebo (pbo) + pemetrexed + platinum once every 3 weeks. ORIENT 12 enrolled (1:1) patients with advanced/metastatic squamous NSCLC to receive either sint 200 mg or pbo + gemcitabine + platinum every 3 weeks. The designs and eligibility of both studies were similar. Pooled analyses were to support the safety assessments by summarizing treatment-related adverse events (TRAE), immune-related TRAE (ir-TRAE) and the association of ir-TRAE with efficacy.

Results

Of 754 patients pooled from two studies (ORIENT 11, n=397; ORIENT 12, n=357), 445 were pooled to the sint arm, and 309 to the pbo arm. There were no meaningful differences in baseline characteristics between subjects with or without ir-TRAE in both arms. The TRAE rates were comparable (sint vs pbo: 85.8% vs 81.6%) between the two arms. Although sint arm had higher ir-TRAE occurrence than pbo arm (sint vs pbo: 42.5% vs 30.7%), ≥ Grade 3 ir-TRAE were comparable in both arms (sint vs pbo: 6.1% vs 4.9%). Notably, higher ir-TRAEs were found in sint arm in rash, hypothyroidism, and immune-mediated pneumonitis. TRAE leading to drug discontinuation (sint vs pbo: 6.5% vs 4.2%) and death (sint vs pbo: 0.9% vs 2.3%) are comparable between the two arms. The exploratory analysis indicated that patients experienced ir-TRAE showed longer PFS and OS than those without ir-TRAE in sint arm (Table). Table: 17P

Efficacy subgroup analysis by ir-TRAE status in sint arm

Conclusions

Sint in combination with chemotherapy demonstrated a tolerable and manageable safety profile in Chinese patients, generally consistent with the pbo population in ORIENT 11 and ORIENT 12 study.

Clinical trial identification

NCT03607539 and NCT03629925.

Legal entity responsible for the study

Lilly Suzhou Pharmaceutical Co., Ltd.

Funding

Lilly Suzhou Pharmaceutical Co., Ltd.

Disclosure

Q. Zhu, H. Li: Financial Interests, Institutional, Writing Engagements, The author is Lilly employee: Lilly. All other authors have declared no conflicts of interest.

Background

Primary results from the phase 3 RATIONALE-307 study (NCT03594747) showed significantly prolonged PFS, higher ORR, and a tolerable safety profile for TIS + chemo as first-line treatment for sq NSCLC. We report results from a post-hoc safety analysis of TIS + chemo vs chemo alone.

Methods

Eligible pts (18–75 years) with treatment-naïve locally advanced or metastatic sq NSCLC were randomized 1:1:1 to Arm A: TIS 200 mg + paclitaxel (P) 175 mg/m² and carboplatin (C) AUC 5 (every 3 weeks [Q3W], day [D] 1); Arm B: TIS + nab-paclitaxel 100 mg/m² (Q3W, D 1, 8, and 15) + C (Q3W, D 1); or Arm C: P + C (Q3W, D 1). Chemo was administered for 4–6 cycles, after which, pts in Arms A and B continued TIS alone, and pts in Arm C were permitted to crossover to receive TIS alone upon disease progression. The safety analysis set (SAS) included all randomized patients who received at least 1 dose of study treatment. The differences between incidence rates of treatment-emergent adverse events (TEAEs) were compared between pts treated with TIS plus chemo vs chemo alone for the first 4–6 cycles of treatment when chemo was administered in combination with TIS (Arms A and B) or alone (Arm C). All statistical analysis results were post-hoc exploratory and P-values are descriptive.

Results

In total, 355 pts were included in the SAS (Arm A: 120; Arm B: 118; Arm C: 117). There were no notable differences in safety results for pts receiving TIS + chemo vs chemo alone (Table). P-values between Arms A vs C, and Arms B vs C were > 0.01. Confidence intervals (CIs) of the differences between Arms A vs C and Arms B vs C all included 0, except between Arms B vs C for TEAEs leading to discontinuation. There was a numerical difference between Arms B vs C for TEAEs leading to discontinuation during the chemo co-administrated period, but this was not clinically meaningful.

Conclusions

TIS + chemo had a tolerable safety profile. TIS did not add toxicity or impact treatment when added to chemo. Table: 18P

Clinical trial identification

NCT03594747.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Tamsin Grewal, MSc, of Ashfield MedComms, an Ashfield Health company, and funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

S.J. Leaw: Financial Interests, Personal, Full or part-time Employment: BeiGene. Y. Yuan: Financial Interests, Personal, Full or part-time Employment: BeiGene. X. Lin: Financial Interests, Personal, Invited Speaker: BeiGene; Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks/Shares: BeiGene. F. Bai: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks/Shares: BeiGene. S. Lu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics, Hutchison, Bristol Myers Squibb, BeiGene; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, Hansoh. All other authors have declared no conflicts of interest.

Background

EGFR exon20ins NSCLC has been associated with poor prognosis, especially after progression on standard of care platinum-based chemotherapy. Amivantamab, an EGFR-MET bispecific antibody, was recently approved for this population. As anti-tumor activity in single-arm studies typically focuses on complete response and partial response (PR), it is of clinical interest to evaluate outcomes in patients (pts) with SD. A landmark analysis was performed to assess outcomes in pts who achieved SD as best response and did not progress on amivantamab at 12 weeks.

Methods

This analysis included 114 pts with post-platinum EGFR exon20ins NSCLC in the CHRYSALIS study (NCT02609776; 30 Mar 2021 data cutoff). Response was assessed by blinded independent central review using RECIST v1.1. Pts alive at landmark of 12 weeks were grouped by response observed at 12 weeks (PR or better [PR+], SD, or progressive disease [PD]). Progression-free survival (PFS) and overall survival (OS) by responder cohort were estimated using the Kaplan–Meier method, and hazard ratios (HR) and 95% confidence intervals (CI) between response cohorts were estimated using Cox proportional hazards regression.

Results

Among pts alive at week 12 (n=107), 42 (39%) had PR+, 52 (49%) had SD, and 13 (12%) had PD. Among pts with PR+ and SD, the median PFS was 12.2 mo and 7.0 mo, respectively. A corresponding improvement in OS was observed in pts who achieved PR+ (median not reached; HR vs PD=0.21 [95% CI: 0.08–0.54]) and SD (median 23.0 mo; HR vs PD=0.33 [95% CI: 0.14–0.77]), relative to those with PD (median 14.0 mo). Table: 19P

Conclusions

Treatment benefit with amivantamab was observed in pts who achieved SD, in addition to those achieving PR+ as best response, with a 67% and 79% reduction in risk rate of death, respectively, compared to those with PD. These data demonstrate the value of disease control, regardless of depth of response, with amivantamab.

Clinical trial identification

NCT02609776.

Editorial acknowledgement

Medical writing assistance was funded by Janssen Global Services LLC and provided by Jennifer A. DiNieri, PhD (System One).

Legal entity responsible for the study

Janssen R&D LLC.

Funding

Janssen R&D LLC.

Disclosure

N. Girard: Financial Interests, Personal, Research Grant: AstraZeneca, AbbVie, Amgen, Boehringer-Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sivan, and Trizell; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, and Sivan; Financial Interests, Personal, Full or part-time Employment, Family member: AstraZeneca. K. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, LOXO, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, JNJ, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: AstraZeneca, MSD Oncology. S. Viteri: Financial Interests, Personal, Advisory Role: AbbVie, Bristol Myers Squibb, Roche, Takeda, AstraZeneca, and MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, MSD, Roche, AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: Roche, OSE Pharma, Bristol Myers Squibb, Merck, Merck Serono, Puma Biotechnology, and Janssen Cilag. C.A. Schioppa: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Diels: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Oguz: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B.H. Rodrigues, N. Rahhali, J. Sermon, F. Ghilotti, T. Li, R.E. Knoblauch, P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B.C. Cho: Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, Bristol Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint medicines; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah Bio; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Other, Founder: Daan Biotherapeutics.

Background

Amivantamab, an EGFR-MET bispecific antibody, is approved for the treatment of advanced EGFR ex20ins NSCLC patients (pts) that have progressed on platinum-based chemotherapy. In this exploratory analysis, we investigated the patterns of progression on amivantamab therapy among pts in this population.

Methods

The CHRYSALIS study (NCT02609776) enrolled pts with advanced NSCLC and allowed the inclusion of pts with treated brain metastases. Baseline brain MRI was required at screening in the dose expansion phase; however, postbaseline surveillance MRIs were performed according to local practice and not required per protocol. Sites of target, non-target, and new lesion progression were reported. This analysis includes 114 post-platinum pts with EGFR ex20ins NSCLC who received amivantamab on or before Jun 4, 2020 (110 from dose expansion).

Results

At the Mar 30, 2021 data cutoff (median follow-up of 12.5 months [range, 0.2–30.5]), RECIST-defined PD was described in 72 of 114 pts (63%), 25 of whom continued amivantamab post progression for a median of 4.2 additional months (range, 1.0–12.5). Baseline brain metastases were reported in 38 of 114 pts. 13 pts (11.4%) had intracranial disease as sole site of progression, 4 had intra- and extracranial progression, and 55 had extracranial progression (most common in lung, bone, lymph node, and liver). 8 of 13 pts with intracranial-only progression had a history of brain metastases at baseline. The median time to progression for pts with intracranial-only progression was 4.5 months (range, 1.4–16.6), as compared with 5.5 months (range, 0.6–24.1) for those pts with systemic progression. 6 of 13 pts with intracranial-only progression underwent stereotactic radiosurgery (SRS) while continuing amivantamab. Adverse events temporally associated with SRS were nausea (10 days after SRS) and fatigue, reported in 1 pt each. For these 6 pts, the median duration of amivantamab treatment after progression was 4.0 months (range, 2.3–6.0).

Conclusions

Intracranial-only progression on amivantamab therapy occurred in 11.4% of pts. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable.

Clinical trial identification

NCT02609776.

Editorial acknowledgement

Medical writing assistance was funded by Janssen Global Services, LLC. and provided by Tracy T. Cao, PhD (Janssen Global Services, LLC.).

Legal entity responsible for the study

Janssen R&D.

Funding

Janssen R&D.

Disclosure

J. Trigo: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel Grant: MSD; Financial Interests, Personal, Invited Speaker: Takeda; Non-Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Merck. B.C. Cho: Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, Bristol Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, Kanaph Therapeutics Inc, Cyrus therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Ownership Interest: DAAN Biotherapeutics. K. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, LOXO, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, JNJ, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: AstraZeneca, MSD Oncology. N. Girard: Financial Interests, Personal, Research Grant: AstraZeneca, AbbVie, Amgen, Boehringer-Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sivan, Trizell; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, Sivan; Financial Interests, Personal, Other, Family member is an employee: AstraZeneca. S. Viteri: Financial Interests, Personal, Advisory Role: AbbVie, Bristol Myers Squibb, Roche, Takeda, AstraZeneca, MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, MSD, Roche, AstraZeneca; Financial Interests, Personal, Other, Travel: Roche, OSE Pharma, Bristol Myers Squibb, Merck, Merck Serono, Puma Biotechnology, Janssen Cilag. P. Garrido: Financial Interests, Personal, Advisory Role: Roche Pharma AG, AstraZeneca, MSD Oncology, Bristol Myers Squibb, Takeda, Lilly, Pfizer, Novartis/Pfizer, Boehringer Ingelheim, AbbVie, Amgen, Bayer, Gebro Pharma, Nordic Group, Boehringer Ingelheim, Janssen Biotech, Janssen Oncology, GlaxoSmithKlein; Financial Interests, Personal, Speaker’s Bureau: Roche Pharma AG, Takeda, AstraZeneca, MSD Oncology, Bristol Myers Squibb, Pfizer, Novartis, Boehringer Ingelheim, Nordic Group, Janssen, Boehringer Ingelheim, Janssen Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche, Bristol Myers Squibb; Financial Interests, Personal, Other: Janssen Oncology, Novartis. M.G. Krebs: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche, Janssen; Financial Interests, Personal, Advisory Role: Roche, Janssen; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, Independent Contractor: Roche, Bayer, Janssen, Seattle Genetics, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Other, Travel: BerGenBio, Immutep. M. Thayu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Xie: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.W. Schnepp: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. A. Londhe: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. N. Leighl: Financial Interests, Personal, Research Grant: Amgen, Array, Astra Zeneca, Bayer, Bristol Myers Squibb, Eli Lilly, EMD Serono, Guardant Health, Inivata, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, Honoraria: Amgen, Boehringer Ingelheim, Bristol Myers Squibb, CADTH, EMD Serono, GlaxoSmithKlein, MSD, Novartis, Puma Biotechnology, Sanofi Genzyme, Takeda; Financial Interests, Personal, Other, Travel Support: AstraZeneca, Roche, Teva-Oncotest.