Background

Sint has been used to treat patients (pts) with advanced NSCLC. This observational study aims to describe the real-world use of Sint and to explore its real-world effectiveness in the first-line (1L) treatment of advanced NSCLC.

Methods

Pts with advanced NSCLC initiating 1L therapy with Sint between Aug 1^st 2018 and Aug 1^st 2020 in 4 tertiary hospitals in mainland China were included. Data in demographic and clinical characteristics, treatment patterns and outcomes were retrospectively collected through medical records. Descriptive analysis was used to describe the baseline characteristics and treatment patterns. Kaplan-Meier method was used to calculate the median progression-free survival (mPFS).

Results

102 pts (85.3% men) were included with mean age of 63.9±9.5 years (median follow-up time: 4.8 months (mo) (range 0.0-32.0)). The most commonly-used treatment regimen was Sint + platinum (Pt) + taxanes (56.0%) for squamous NSCLC (sqNSCLC) and Sint + Pt + pemetrexed (38.5%) for non-squamous NSCLC (nsqNSCLC) (Table). The mPFS was 15.8 mo (95% CI: 11.5-NA) and 12.0 mo (95% CI: 6.3-NA) respectively for sqNSCLC and nsqNSCLC pts. The mPFS was 17.0 mo (95% CI 11.5-NA) in sqNSCLC pts using Sint + Pt + taxanes as 1L therapy and 7.2 mo (95% CI: 0.7-NA) in nsqNSCLC pts. The ORR was 57.1% and 53.6% respectively for sqNSCLC and nsqNSCLC pts. Table: 71P

Baseline characteristics and treatment pattern of NSCLC

Conclusions

For sqNSCLC pts with Sint as 1L therapy, taxanes and gemcitabine are more preferred, while for nsqNSCLC pts, pemetrexed is more often combined. The real-world effectiveness of 1L treatment of Sint for advanced NSCLC pts is promising from the study.

Legal entity responsible for the study

Eli Lilly China.

Funding

Lilly (Shanghai) Management Co., Ltd.

Disclosure

L. Zhang: Financial Interests, Personal and Institutional, Full or part-time Employment, employees of Lilly China and own Lilly stock shares: Eli Lilly China; Financial Interests, Personal and Institutional, Stocks/Shares, employees of Lilly China and own Lilly stock shares: Eli Lilly China. L. Liu: Financial Interests, Personal and Institutional, Full or part-time Employment, employees of Lilly China and own Lilly stock shares: Eli Lilly China; Financial Interests, Personal and Institutional, Stocks/Shares, employees of Lilly China and own Lilly stock shares: Eli Lilly China. J. Li: Financial Interests, Personal and Institutional, Full or part-time Employment, employees of Lilly China and own Lilly stock shares: Eli Lilly China; Financial Interests, Personal and Institutional, Stocks/Shares, employees of Lilly China and own Lilly stock shares: Eli Lilly China. W. Ding: Financial Interests, Institutional, Advisory Role, received Lilly’s sponsorship: Happy Life Technology. All other authors have declared no conflicts of interest.

Background

Consolidation immunotherapy (IO) after chemoradiation is the standard of care for stage III uNSCLC. Addition of IO-based induction therapy may further improve outcome, partly by enabling surgery. SHR-1701 is a novel anti-PD-L1/TGFβRII fusion protein. We assessed neoadjuvant SHR-1701 ± chemo, followed by surgery or RT in untreated stage III uNSCLC without EGFR/ALK alterations.

Methods

Pts were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) ± chemo (paclitaxel 175 mg/m² Q3W + carboplatin AUC=5 Q3W). Pts with PD-L1 TPS <50% received combo-therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combo-therapy (arm B) or SHR-1701 alone (arm C). After assessment by MDT, pts received surgery or definitive RT (60 Gy/30 fractions) + concurrent cisplatin (30 mg/m² QW), followed by SHR-1701 for 16 cycles. The primary endpoints were post-induction ORR and event-free survival (EFS).

Results

107 pts were enrolled (arm A/B/C, n=88/9/10; median age, 59 y; squamous NSCLC, 76.6%; stage IIIA/B/C, 25.2%/43.9%/29.9%). In all pts, the post-induction and best overall ORR were 56.1% (95% CI 46.2-65.7) and 70.1% (60.5-78.6). mEFS was 18.2 mo (95% CI 11.8-not reached [NR]). Efficacy by study arm is shown in Table 1. 27 (25.2% of 107; baseline stage IIIA/B/C, 37.0%/44.4%/18.5%) pts underwent surgery (lobectomy/bilobectomy/pneumonectomy, 88.9%/7.4%/3.7%); all achieved R0 resection. Among them, 12 (44.4%) MPR and 7 (25.9%) pCR were recorded. Nodal downstaging was seen in 14 pts (51.9%; pN2 to pN0/1, 8/14 [57.1%]; pN3 to pN0-2, 6/9 [66.7%]). mEFS was NR in resected pts. Grade ≥3 TRAEs occurred in 77 (72.0%) pts; all with frequency ≥10% were hematotoxicities. No new safety signals were identified. Table: LBA5

Efficacy by study arm

Conclusions

SHR-1701 ± chemo showed promising antitumor activity with a tolerable safety profile in stage III uNSCLC. Some pts could switch from unresectable to resectable and get much better efficacy. Phase 3 investigation is warranted.

Clinical trial identification

NCT04580498.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals, Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals, Co., Ltd.

Disclosure

Y. Wu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Research Grant: Boehringer Ingelheim, Roche, Pfizer, Bristol Myers Squibb. J. Shuang, L. Song, W. Shi: Financial Interests, Personal, Full or part-time Employment: Hengrui. All other authors have declared no conflicts of interest.

Background

First-line durvalumab (D) plus platinum–etoposide (EP) significantly improved overall survival versus chemotherapy group in CASPIAN phase III study. We initiated a phase IIIb study to assess the safety and efficacy of D+EP in Chinese patients with ES-SCLC.

Methods

ORIENTAL is a single arm, multicenter, phase IIIb study. Treatment-naive ES-SCLC with ≥18 years of age and ECOG PS 0-2 were eligible. Durvalumab (1500 mg) was concurrently administered with first-line EP every 3 weeks for 4 to 6 cycles, followed by Durvalumab maintenance every 4 weeks until progressive disease or unacceptable toxicity. The primary endpoint was immune-mediated adverse events (imAE), the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs).

Results

Between Nov. 2020 and Aug. 2021, 151 eligible patients from 32 sites in China were enrolled and received study treatment. At the data cut-off (Feb. 28^th, 2022), 38 (25%) patients were still on study treatment. The median age was 66 years (range 43-82). 86.1% of patients were males, 4% were ECOG PS 2, and 13.2% had brain metastasis. The median cycle number of durvalumab was 7 (1-18). Any-cause AEs occurred in 97.4% of patients, and the incidence of imAE was 21.9% [95%CI 15.5-29.3]. AEs ≥ grade 3 occurred in 46.4% of patients, the most common ones were anemia (17.2%), platelet count decreased (7.3%), myelosuppression (6.0%), neutrophil count decreased (4.0%), white blood cell count decreased (3.3%), and hypokalemia (2.6%). There were discontinuations of study treatment in 12 patients (7.9%) and 5 deaths (3.3%) due to treatment-related AEs. ORR was 75.5% [95%CI 67.8-82.1], including two CRs. The median PFS was 6.3 months [95%CI 5.8-6.5), with a median follow-up of 5.7 months. The median OS was not reached yet [95%CI 9.6-NA].

Conclusions

ORIENTAL is the largest study to evaluate the safety and efficacy of D+EP in Chinese ES-SCLC patients to date. The preliminary safety profile and efficacy data are consistent with the CASPIAN study and support D+EP as the standard of care in ES-SCLC.

Clinical trial identification

NCT04449861.

Legal entity responsible for the study

The authors.

Funding

AstraZeneca China.

Disclosure

All authors have declared no conflicts of interest.

Background

Immunotherapy combined with chemotherapy as first-line treatment in advanced ESCC has been the standard of care. Previously results demonstrated anlotinib, whether combined with chemotherapy as first-line regimen or monotherapy as second-line treatment, had encouraging efficacy and manageable toxicity in advanced ESCC. TQB2450 is a humanized anti-PD-L1 monoclonal antibody, which could recovery T-cells activity and enhance immune responses by preventing the binding of PD-L1 to PD-1 and B7.1 receptors on the surface of T cells. Here, we conducted a phase II trial to evaluate the efficacy and safety of anlotinib combined with TQB2450, cisplatin and paclitaxel as first-line therapy in advanced ESCC.

Methods

Eligible patients (pts) with advanced ESCC who had not previous systemic therapy received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1∼14, q3w) combined with paclitaxel (135mg/m², iv, d1, q3w) and cisplatin (60∼75mg/m², iv, d1∼3, q3w) for 4 to 6 cycles as initial therapy. Patients, who did not have progressive disease (PD), continued received anlotinib (10mg, po, d1∼14, q3w) and TQB2450 (1200mg, iv, d1, q3w) as maintenance treatment until PD or unacceptable toxicity. The primary endpoint was PFS. Secondary endpoints were iPFS (iRECIST), ORR (RECIST 1.1), DCR, DOR and safety.

Results

As of 31 May, 2022, 38 pts were enrolled with a median age of 64 years (range 41-74), male (78.9%) and ECOG PS 1 (78.9%). Of 25 evaluable pts, 1 pts had complete response, 20 pts reached partial response and 4 pts had stable disease. The ORR was 84.0% (95%Cl 63.9%-95.5%) and the DCR was 100.0% (95%Cl: 86.3%-100.0%). Median PFS was not reached. ≥ Grade 3 treatment-related adverse events (TRAEs) was 57.9% (22/38), which mainly included neutropenia (42.1%), leukopenia (18.4%) and hypertension (18.4%). 11 pts (28.9%) suffered from serious AEs. AEs led to discontinuation of TQB2450 in 7.9% and anlotinib in 7.9% of enrolled patients.

Conclusions

TQB2450 plus anlotinib combined with paclitaxel and cisplatin showed significant efficacy and manageable toxicities as first-line treatment in advanced ESCC, which might provide a new treatment strategy for those.

Clinical trial identification

NCT05013697.

Legal entity responsible for the study

The authors.

Funding

Chia Tai-Tianqing Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

Background

Treatment option is limited for EGFR-mutated NSCLC after failure to EGFR TKIs. This multicenter, open-label, phase II study aims to evaluate the efficacy and safety of TIS plus chemo (cohort 1) or TIS plus chemo and bevacizumab (cohort 2) in EGFR-mutated nsq-NSCLC pts failed to EGFR TKI therapies. Herein, the primary analysis of cohort 1 is reported.

Methods

In cohort 1, pts with EGFR sensitizing mutations who had failed prior EGFR-TKIs received TIS plus carboplatin and nab-paclitaxel (induction), followed by TIS plus pemetrexed (maintenance). Primary endpoint was 1-year PFS rate; the planned sample size was 66 with a historical control of 7% (chemo), an expected value of 20%, one-sided α of 0.05, and power of 85%.

Results

From Jul 2020 to Dec 2021, 69 pts were enrolled; 39 pts (56.5%) harbored EGFR exon 19del; 28 pts (40.6%) had exon 21 L858R. 34 pts (49.3%) had progression on both 1^st /2^nd and 3^rd EGFR-TKIs. As of 30 Jun 2022 (median follow-up, 8.2 months), 23.2% (n=16) of pts remained on treatment. Among 62 pts in EAS (Table), the confirmed ORR and DCR were 50.0% (95% CI 37.0-63.0%) and 87.1 % (95% CI 76.1-94.3%), respectively. Median PFS was 7.6 (95% CI, 6.4-9.8) months, with a 1-year PFS rate of 23.8% (90% CI, 13.1-36.2%). Pts with L858R mutation or having prior 1^st/2^nd EGFR-TKIs tended to have a longer PFS compared with pts with EGFR exon 19del mutation or progressed on 1^st /2^nd and 3^rd EGFR-TKIs. Median OS was not reached (95% CI, 14.0-NE), and 1-year OS rate was 74.5% (95% CI, 56.5-86.0%). Safety profile was consistent with previous reports of TIS plus chemo in pts with EGFR-wt NSCLC. Grade 3-4 TEAEs occurred in 40.6% (28/69) of pts. 27.5% (19/69) of pts experienced irAEs; grade 3-4 irAEs occurred in 5 (7.2%) pts. Table: 136P

Conclusions

The study met the primary endpoint for cohort 1. TIS plus chemo is effective with acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure.

Clinical trial identification

NCT04405674.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B. Han: Financial Interests, Institutional, Research Grant: AstraZeneca, BeiGene, Roche, Innovent Biologics, Chia Tai Tianqing Pharmaceutical. All other authors have declared no conflicts of interest.

Background

Mucin-16 is a cell surface glycoprotein that is overexpressed in epithelial OC. Ubamatamab (REGN4018) is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by facilitating contact between cancer cells and T cells. Cemiplimab is an anti–programmed cell death-1 monoclonal antibody. The phase 1 study in patients with recurrent OC found ubamatamab monotherapy had an acceptable safety profile, durable clinical activity across a range of doses (as measured by RECIST and cancer antigen 125 [CA-125] response rates), and linear pharmacokinetics up to 800 mg weekly intravenous (IV)¹. These clinical data support further evaluation of a once every 3-week (Q3W) regimen of ubamatamab alone and in combination with cemiplimab.

Trial Design

In phase 2, up to 150 patients with advanced platinum-resistant OC and elevated serum CA-125 will be randomised to three IV arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 patients. Any arm with ≥3 objective responses will be expanded to 50 patients. In this dose expansion phase the primary endpoint will be the objective response rate for each arm as defined by RECIST 1.1 criteria. Secondary endpoints include evaluation of duration of response and progression-free survival as well as further evaluation of safety and pharmacokinetics. Exploratory endpoints include evaluation of baseline tumour MUC16 immunohistochemistry expression and other biomarkers as predictors of response. The impact of ubamatamab on quality of life and physical functioning will also be assessed. Final data are pending for this TiP. Reference 1: Annals of Oncology (2022) 33 (suppl_7): S235-S282. 10.1016/iotech/iotech1054.

Clinical trial identification

NCT03564340.

Editorial acknowledgement

Medical writing support was provided by Rachel McGrandle, BSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc.

Funding

Regeneron Pharmaceuticals, Inc.

Disclosure

K.N. Moore: Financial Interests, Personal, Advisory Role: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Caris, Elevar, Eisai, Genentech/Roche, GSK/Tesaro, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Mereo, Myriad, Mersana, Novocure, Novartis, Tarveda, Verastem and VBL Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Regeneron, Novocure, Genentech/Roche, AbbVie, GSK/Tesaro, Immunogen, PTC Therapeutics, Merck, Lilly, Mereo, Artios and Daichii. S. Bouberhan: Financial Interests, Personal, Advisory Role: ImmunoGen. E. Hamilton: Financial Interests, Institutional, Research Grant: Regeneron, AbbVie, Acerta Pharma, ADC Therapeutics, Akesobio Australia, Amgen, Aravive, ArQule, Arvinas, AstraZeneca, AtlasMedX, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Dana Farber Cancer Inst, Daiichi Sankyo, Deciphera, eFFE; Financial Interests, Institutional, Advisory Role: Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roc. J. Liu: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Eisai, EpsilaBio, Genentech/Roche, GlaxoSmithKline and Regeneron Pharmaceuticals, Inc.; Financial Interests, Institutional, Research Grant: 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, Vigeo Therapeutics and Zentalis. R.E. O'Cearbhaill: Financial Interests, Personal, Other, Personal fees: Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, Immunogen, Curio and MJH; Financial Interests, Personal, Other, Travel support for meeting: Hitech Health; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Role: PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca); Non-Financial Interests, Personal, Advisory Role: Carina Biotech; Financial Interests, Institutional, Research Grant: Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, AbbVie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma and. D. O'Malley: Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), Ambry, Myriad Genetics, Tarveda, Novartis, Rubis, Elevar, Takeda, Toray, INXMED, Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics and Celsion Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., Cerulean Pharma, Bristol Myers Squibb Co., Serono Inc., TRACON Pharmaceuticals, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health C. S. Yoo: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Peterman: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. P. Goncalves: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. T. Schmidt: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Zhu: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Uldrick: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. E.A. Miller: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.

Background

Novel immunotherapy has revolutionized the landscape of cancer therapy. Growing evidence has revealed the importance of tumor microenvironment (TME) and how it may impact the response to immunotherapy. Emerging data has suggested immune biomarkers based on co-expression patterns and spatial distribution will improve predictive performance to the efficacy of immunotherapy. mIF approach is well suited to such a need. The deep profiling and spatial characterization provided by a high-plex mIF assay is a powerful tool to identify predictive biomarkers. And low-plex mIF technology offers a faster turn-around time and could potentially be translated into clinical practice.

Methods

In this study, 40 CRC samples were analyzed using MultiOmyx^TM and PhenoImager^TM assays. For MultiOmyx analysis, the samples were stained with a comprehensive immunoncology (IO) panel including 17 biomarkers. The expression and spatial distribution of each biomarker was studied with proprietary deep-learning based image analysis. Adjacent sections of each sample were stained by two PhenoImager panels: MOTiF kit and a 5-plex custom assay for identification of mature tertiary lymphoid structures (TLS). Biomarker classification was performed using Indica Halo analytics algorithm.

Results

PhenoImager panels successfully identified different subtypes of tumor infiltrating lymphocytes (TILs) and mature TLS within the TME. MultiOmyx analysis was able to provide a comprehensive characterization of immune markers and further classification of TLS into different maturation stages based on biomarker expression and spatial organization of immune cells. To assess cross-platform concordance, correlation coefficient was calculated using cell density data generated by each platform. Direct correlation was observed for the markers used in this study.

Conclusions

This study provides a use case on complementary mIF platforms to support translational studies at different stages. The data indicates that it can effect a practical path with use of a high-plex mIF assay for discovery of novel biomarkers and then bridge into a low-plex mIF assay to further clinical understanding and practice.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.