- Linda Coate (Limerick, Ireland)
LBA4 - GEMSTONE-302: A phase III study of platinum-based chemotherapy (chemo) with placebo or CS1001, an anti-PDL1 antibody, for first-line (1L) advanced non-small cell lung cancer (NSCLC) (ID 415)
- Caicun Zhou (Shanghai, China)
Abstract
Background
CS1001, a full-length, fully human PD-L1 targeted IgG4 (s228p) mAb, was well tolerated and had demonstrated promising anti-tumor activities across a range of cancers including NSCLC in phase Ia/Ib study. GEMSTONE-302 is a randomized, double-blind, phase III study to compare the efficacy and safety of chemo with or without CS1001 as 1L treatment for advanced NSCLC.
Methods
Eligible pts with untreated advanced NSCLC were stratified by histology (sq vs nsq), PD-L1 expression (≥1% vs <1%), and ECOG PS (0 vs 1) and randomized 2:1 to receive CS1001 (1200 mg, Q3W, IV)/placebo + chemo up to 4 cycles, followed by CS1001 or placebo maintenance up to 2 yrs. In nsq pts, pemetrexed was also given as maintenance therapy. The primary endpoint is investigator-assessed PFS (RECISIT v1.1).
Results
A total of 479 pts (320 in CS1001+chemo, 159 in placebo+chemo) were enrolled in the study. Baseline characteristics were balanced between 2 arms. As of 8 Jun 2020, at the pre-planned PFS interim analysis (median follow-up 8.67 vs 8.34 mo), the mPFS was significantly prolonged in the CS1001+chemo arm (stratified HR 0.50 [0.39-0.64], p<.0001; mPFS 7.8 vs 4.9 mo). ORR was 61.4% and 39.2% in CS1001+chemo and placebo+chemo arms, respectively. OS data was immature, but a clinical benefit trend was observed, (stratified HR 0.66 [0.44-0.97]; mOS NR vs 14.75 mo). Subgroup analyses demonstrated clinical benefits across histology and PD-L1 expression levels. Grade ≥3 TEAEs were reported in 61.9% and 61.6% of pts in CS1001+chemo and placebo+chemo arms, respectively. The 2 arms had similar safety profile, with the exception of mostly Grade 1 and 2 immune-related AEs in CS1001+chemo arm. No new unexpected safety signals were found.
Conclusions
This is the first phase III trial conducted in China on an anti-PD-L1 mAb plus chemo that enrolls advanced, treatment-naive sq and nsq NSCLC pts. CS1001 combined with chemo shows statistically significant and clinically meaningful benefit in PFS with a well-tolerated safety profile against chemo across histology and PD-L1 expression levels. It will potentially become a new SOC for 1L treatment of advanced NSCLC once receiving regulatory approval.
Clinical trial identification
NCT03789604.
Legal entity responsible for the study
CStone Pharmceuticals.
Funding
CStone Pharmaceuticals.
Disclosure
P. Li, J. Wang, B. Sun: Shareholder/Stockholder/Stock options, Full/Part-time employment: CStone Pharma. D. Lu: Full/Part-time employment: CStone Pharma. J. Yang: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: CStone Pharma.
375O - Final efficacy results from IMpower132: First-line atezolizumab + chemotherapy in patients with stage IV non-squamous NSCLC (ID 379)
- Makoto Nishio (Tokyo, Japan)
Abstract
Background
The Phase III IMpower132 study, evaluating first line pemetrexed plus carboplatin/cisplatin with or without atezolizumab in Stage IV non-squamous NSCLC without EGFR or ALK driver mutations, has met its PFS endpoint with an HR of 0.60 (95% CI: 0.49, 0.72; P < 0.0001; Papadimitrakopoulou, WCLC 2018). Here we present the final OS and safety results.
Methods
Patients were randomised 1:1 to 4 or 6 cycles of carboplatin AUC 6 mg/mL/min or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W alone (arm PP) or with atezolizumab 1200 mg Q3W (arm APP), followed by pemetrexed (PP) or atezolizumab + pemetrexed (APP) maintenance. Investigator-assessed PFS and OS were co-primary endpoints. Efficacy by PD-L1 status was an exploratory endpoint.
Results
At data cutoff (18 July 2019), 292 patients in arm APP and 286 patients in arm PP had a median follow-up of 28.4 mo. Updated median PFS was 7.7 months (APP) vs 5.2 months (PP); HR, 0.56 (95% CI: 0.47, 0.67). Final OS data are in the table. 38.7% (APP) vs 57.3% (PP) of patients received subsequent anti-cancer therapy, including immunotherapy in 5.5% vs 45.8%. Grade ≥ 3 treatment-related adverse events (AEs) occurred in 58.4% (APP) vs 43.1% (PP) of patients, including immune-mediated AEs in 6.9% (APP) vs 4.7% (PP) of patients. NE, not estimable. a Stratified. b PD-L1 status available in 60% of pts. PD-L1–high: ≥ 50% TC or ≥ 10% IC; PD-L1–low: ≥ 1% and < 50% TC or ≥ 1% and < 10% IC; PD-L1–negative: < 1% TC and < 1% IC.
APP PP ITT n = 292 n = 286 mOS (95% CI), mo 17.5 (13.2, 19.6) 13.6 (11.0, 15.7) HRa (95% CI; P value) 0.86 (0.71, 1.06; P = 0.155) 12-Month OS 59.7% 55.0% 24-Month OS 39.1% 34.0% PD-L1–highb n = 25 n = 20 mOS (95% CI), mo NE (22.4, NE) 26.9 (4.7, NE) HR (95% CI) 0.73 (0.31, 1.73) PD-L1–lowb n = 63 n = 73 mOS (95% CI), mo 12.7 (8.7, 18.2) 16.2 (9.6, 22.6) HR (95% CI) 1.18 (0.80, 1.76) PD-L1–negativeb n = 88 n = 75 mOS (95% CI), mo 15.9 (11.6, 22.6) 10.5 (8.1, 13.5) HR (95% CI) 0.67 (0.46, 0.96)
Conclusions
IMpower132 had met its co-primary PFS endpoint at the primary analysis but did not meet its co-primary OS endpoint in this final analysis. Atezolizumab + carboplatin/cisplatin + pemetrexed was well tolerated, and no new safety signals were identified.
Clinical trial identification
NCT02657434.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Chris Lum, PhD of Health Interactions and by Kshipra Desai, 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
M. Nishio: Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Perosnal Fees: Ono Pharmaceutical; BMS; Pfizer; Chugai Pharmaceutical; Eli Lilly; Taiho Pharmaceutical; AstraZeneca; Boehringer-Ingelheim; MSD; Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Personal Fees: Sankyo Healthcare; Research grant/Funding (institution), Personal Fees: Merck Serono; Research grant/Funding (institution), Grants: Astellas. F. Barlesi: Honoraria (self), Personal Financial Interest, Institutional Financial Interest, Non-Financial Interest: AstraZeneca; BMS; Merck; Pierre Fabre; Roche; Honoraria (self), Personal Financial Interest, Institutional Financial Interest: Bayer; Boehringer-Ingelheim; Eli Lilly Oncology; Novartis; MSD; Pfizer; Takeda; Honoraria (self), Institutional Financial Interest: AbbVie; ACEA; Amgen; Eisai; Genentech; Ipsen; Ignyta; Innate Pharma; Loxo; MedImmune; Sanofi-Aventis. R. Bordoni: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Merck; Speaker Bureau/Expert testimony: Genentech; Speaker Bureau/Expert testimony: Guardant Health. J. Goldschmidt: Advisory/Consultancy: Amgen; Speaker Bureau/Expert testimony: Bristol-Myers Squibb. S. Novello: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Boehringer-Ingelheim; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: BMS. F.J. Orlandi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Merck & Co.; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Celltrion; Advisory/Consultancy: Bristol-Myers Squibb; Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Research grant/Funding (institution): MabXience; Research grant/Funding (institution): Sanofi. R. Sanborn: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Amgen; Advisory/Consultancy: Seattle; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Celldex; Research grant/Funding (self): Merck; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): MedImmune. Z. Szalai: Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer-Ingelheim; Bristol-Myers Squibb; Roche; Pfizer; AstraZeneca; Chiesi; MSD. D. Mendus, L. Wang, X. Wen: Full/Part-time employment: Genentech, Inc. M. McCleland: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. T. Hoang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. S. Phan: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. M. Socinski: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech, Inc.; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Guardant; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Research grant/Funding (institution): Novartis. All other authors have declared no conflicts of interest.
Invited Discussant abstracts LBA4 and 375O (ID 1124)
- Martin Reck (Grosshansdorf, Germany)
LIVE Q&A (ID 1126)
- Linda Coate (Limerick, Ireland)
376O - Randomized, multicenter trial of autologous cytokine-induced killer cell immunotherapy plus chemotherapy for squamous non-small cell lung cancer: NCT01631357 (ID 343)
- Liang Liu (Tianjin, China)
Abstract
Background
There is no multicenter clinical study about cytokine-induced killer (CIK) cells in lung cancer. This randomized, multicenter trial was designed to evaluate the efficacy of CIK cell immunotherapy combination with chemotherapy in patients with advanced squamous non-small-cell lung cancer (NSCLC).
Methods
In this phase II trial, 90 patients with untreated, stage IIIB/IV squamous NSCLC were randomized to autologous CIK cell immunotherapy plus gemcitabine and cisplatin (CIK-CT group, n = 45), or gemcitabine and cisplatin (CT group, n = 45). The primary endpoint was progression-free survival (PFS) and secondary endpoint was overall survival (OS) evaluated by Kaplan–Meier analyses and treatment hazard ratios (HRs) with the Cox proportional hazards model.
Results
After a median follow-up of 29.3 months, the median PFS was 8.7 months (95% CI, 7.1 to 10.3) in the CIK-CT group and 4.0 months (95% CI, 3.1 to 5.0) in the CT group (HR, 0.26; 95% CI, 0.16 to 0.43; P < .001). The median OS was 21.0 months (95% CI, 17.8 to 24.2) in the CIK-CT group and 10.3 months (95% CI, 7.9 to 12.1) in the CT group (HR, 0.22; 95% CI, 0.13 to 0.40; P < .001). The objective response rate was 62.2% (95% CI, 47.9% to 76.5%) in the CIK-CT group and 31.1% (95% CI, 17.4% to 44.8%) in the CT group (P < .001). The adverse events of grade 3 or higher were 33.3% and 42.2% in the CIK-CT group and CT group, respectively.
Conclusions
These data suggested that the addition of CIK cell immunotherapy to chemotherapy resulted in significantly longer PFS and OS than chemotherapy alone in patients with previously untreated, advanced squamous NSCLC.
Clinical trial identification
NCT01631357.
Legal entity responsible for the study
The authors.
Funding
The National Key Technologies R&D Program of China grant Awards No. 2015BAI12B12 (to Xiubao Ren).
Disclosure
All authors have declared no conflicts of interest.
377O - A randomized double-blind phase III study of niraparib versus placebo as maintenance therapy in extensive-stage small cell lung cancer (ID 794)
- Xinghao Ai (Shanghai, China)
Abstract
Background
Niraparib is a highly selective PARP-1/2 inhibitor approved by FDA for the maintenance therapy of ovarian cancer. It also showed promising activity as maintenance treatment in platinum sensitive SCLC PDX models. ZL-2306-005 is a randomized, double-blind, multicenter phase Ⅲ study to evaluate the efficacy and safety of niraparib (nira) versus placebo (pla) as first line (1L) maintenance therapy in extensive-stage SCLC (ES-SCLC) patients.
Methods
Patients (pts) with ES-SCLC, ECOG PS 0 or 1, CR/PR after 4 cycles of 1L etoposide/cisplatin or etoposide/carboplatin were enrolled. Prophylactic cranial irradiation (PCI) was optional. Pts were randomized 2:1 to receive nira or pla once daily as maintenance therapy until progression or unacceptable toxicity. Nira started with 300mg QD for pts with baseline body weight ≥77 kg and platelet count ≥150,000/μL, otherwise 200 mg QD. Stratified factors were gender, LDH level and PCI history. The primary endpoints were PFS by blinded independent central review (BICR) and OS; the secondary endpoints were PFS by investigator, CFI, QoL, safety and tolerability.
Results
From Jul 2017 to Feb 2020, 272 pts were screened in 34 sites, of whom 185 were randomized and dosed according to protocol, 125 in nira arm and 60 in pla arm. The study was early terminated due to landscape changed by immunotherapy in ES-SCLC. At the data cutoff: 20 Mar 2020, there were 167 pts discontinued from the treatment and 70 pts died. Median PFS (BICR) was 1.54 m (1.41, 2.69) in nira arm and 1.36 m (1.31, 1.48) in pla arm (HR 0.66; 95% CI [0.46, 0.95]; p= 0.0242). Median OS was 9.92 m (9.33, 13.54) in nira arm and 11.43 m (9.53, NE) in pla arm (HR 1.03; 95% CI [0.42, 1.73]; p = 0.9052). Grade≥3 treatment-related AEs (TEAEs) was 34.4% in nira arm vs. 25% in pla arm. No patient had a TEAE leading to death.
Conclusions
Niraparib has modest improvement in PFS compared to placebo in 1L ES-SCLC maintenance with manageable and tolerated safety profile. OS benefit was not observed based on immature data. The value of adding niraparib to immunotherapy needs further investigation.
Clinical trial identification
NCT03516084.
Legal entity responsible for the study
Zai Lab.
Funding
Zai Lab. Shanghai Science and Technology Commission (18DZ1910700).
Disclosure
B. Zhang, D. Zhang: Full/Part-time employment: Zai Lab. All other authors have declared no conflicts of interest.
Invited Discussant abstracts 376O and 377O (ID 1125)
- Anne-Marie C. Dingemans (Rotterdam, Netherlands)
LIVE Q&A (ID 1127)
- Linda Coate (Limerick, Ireland)