Despite treatment (tx) with anti–PD-L1/PD-1 (αPD-(L)1) and platinum-based chemo, mNSCLC often progresses, suggesting a need for new second/third-line tx options. The TKI cabo may enhance αPD-(L)1 efficacy by promoting an immune-permissive environment. CONTACT-01 is a multicentre, randomised, open-label Ph3 study of atezo (anti–PD-L1) + cabo vs doc in pts with mNSCLC previously treated with αPD-(L)1 + chemo.
Eligible pts had ECOG PS 0-1, histologically or cytologically confirmed mNSCLC with progression after αPD-(L)1 + chemo (concurrent or sequential; regardless of response to prior αPD-(L)1) and any known PD-L1 status (or available tissue for central testing). Pts were randomised 1:1 to atezo 1200 mg IV q3w + cabo 40 mg PO qd or doc 75 mg/m2 IV q3w. Stratification factors were sq vs nsq histology and sequence of prior NSCLC regimens. The primary EP was OS (ITT). Key secondary EPs were PFS, ORR, DOR and safety.
Of 366 pts assigned to either atezo + cabo (n = 186) or doc (n = 180), 61% and 71% had ECOG PS 1, and 74% and 76% had nsq histology, respectively; median age was 64 and 66 y. At data cutoff 28 Sep 2022, minimum follow-up was 10.9 mo. No statistically significant OS benefit was seen with atezo + cabo vs doc (table). Median tx duration was 4.2 mo (range, 0–20; atezo), 3.9 mo (0–21; cabo) and 2.1 mo (0–19; doc). All-cause AEs occurred in 98% (G3-4, 48%) of safety-evaluable pts in the atezo + cabo arm and 94% (G3-4, 45%) in the doc arm and led to discontinuation in 17% and 14% of pts, respectively. G3-4 AEs of special interest for atezo were seen in 15% and 4% (G5 in 1% and 0%) and for cabo in 14% and 2% (G5 in 2% and 2%), respectively. G5 tx-related AEs occurred in 4 pts (2%) in the atezo + cabo arm and 1 pt (<1%) in the doc arm.
| Endpoint | Atezo + cabo (n = 186) | Doc (n = 180) |
|---|---|---|
| OS events, n (%) | 114 (61) | 106 (59) |
| Median OS, months (95% CI) | 10.7 (8.8, 12.3) | 10.5 (8.6, 13.0) |
| Stratified HR (95% CI) | 0.88 (0.68, 1.16) | |
| P value | 0.3668 | |
| PFS events, n (%) | 162 (87) | 150 (83) |
| Median PFS, months (95% CI) | 4.6 (4.1, 5.6) | 4.0 (3.1, 4.4) |
| Stratified HR (95% CI) | 0.74 (0.59, 0.92) | |
| ORR, % (95% CI) | 11.8 (7.6, 17.4) | 13.3 (8.7, 19.2) |
| DOR, months (95% CI) | 5.6 (3.1, 10.3) | 4.3 (3.3, 5.6) |
AE, adverse event; DOR, duration of response; EP, endpoint; G, Grade; HR, hazard ratio; ITT population, intent-to-treat population; nsq, nonsquamous; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; sq, squamous; TKI, tyrosine kinase inhibitor.
In this final OS analysis of CONTACT-01, atezo + cabo was not superior to doc in the ITT population. No new safety signals arose.
NCT04471428.
Editorial support for this abstract was provided by Michael Williams, PhD, of Health Interactions, Inc.
F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
J. Neal: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Eli Lilly and Company, Calithera Biosciences, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics; Financial Interests, Institutional, Funding: Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GSK, Janssen, AbbVie; Other, Personal, Other, Honoraria: CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, HMP Education. N. Pavlakis: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, MSD, Merck KgA, BMS, AstraZeneca, Takeda, Pfizer, Roche, Amgen, BeiGene, Novartis, AllVascular; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Bayer, Roche, Pfizer. Y. Goto: Financial Interests, Personal, Other, Honoraria (lecture fees): AstraZeneca, Pfizer, Novartis, Eli Lilly Japan. S.M. Lim: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BridgeBio Therapeutics, Roche, GSK, Jiansu Hengrui; Financial Interests, Personal, Invited Speaker: Oscotec. G. Mountzios: Financial Interests, Personal, Advisory Board: Roche, BMS, Takeda, Janssen; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Novartis, Amgen. E. Fountzilas: Financial Interests, Personal, Other, Travel Grant: Merck, Pfizer, K.A.M. Oncology/Hematology; Financial Interests, Personal, Other, Speaker's fees: Roche, Leo, Pfizer; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, Inc. D.C.C. Christoph: Financial Interests, Personal and Institutional, Other, Grants or contracts, consulting fees, payment or honoraria, payment for expert testimony, support for attending meetings and/or travel, participation on a data safety monitoring board/advisory board, and other payments made to institutions: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda. A. Bearz: Financial Interests, Personal, Advisory Role, Speaking fees: Pfizer, Takeda, Boehringer Ingelheim, Merck Sharp & Dohme, AstraZeneca, Eli Lilly. X. Quantin: Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Other, Educational support: AstraZeneca. R. Palmero: Financial Interests, Personal, Invited Speaker: Guardant Health, Pfizer, Roche, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Merck-Sharp-Dome; Financial Interests, Personal, Other, ravel/meeting attendance expenses: Merck-Sharp-Dome, Roche; Financial Interests, Personal, Advisory Role, membership of data safety monitoring: Boehringer Ingelheim, Roche. V. Antic: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. E. Chun: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. T. Rao Edubilli: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. Y. Lin: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. M. Huseni: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. C. Scheffold: Financial Interests, Personal, Full or part-time Employment: Exelixis. P. Vervaet: Financial Interests, Personal, Full or part-time Employment: Exelixis. T. Newsom-Davis: Financial Interests, Personal, Other, Consulting fees: Takeda, Pfizer, Roche, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Chugai, Janssen, Eli Lilly, Merck, MSD, Novartis, and Otsuka; Financial Interests, Personal, Other, Honoraris for lectures/presentations: Takeda, Pfizer, Roche, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Chugai, Janssen, Eli Lilly, Merck, MSD, Novartis, and Otsuka; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche, and Takeda; Financial Interests, Personal, Leadership Role, Chair of the Independent Monitoring Committee: Roche, BluePrint Medicines. All other authors have declared no conflicts of interest.