LBA63 - SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC)

Background

Checkpoint inhibitor (CPI) therapy can lead to antitumor responses and prolonged survival in NSCLC, but most patients (pts) who initially benefit acquire CPI resistance with disease progression. Sitravatinib (sitra) is a receptor tyrosine kinase inhibitor that can resensitize tumors to CPI by shifting the tumor microenvironment towards a less immunosuppressive state and, combined with nivolumab (nivo), may overcome acquired CPI resistance and improve outcomes vs chemotherapy.

Methods

In the Phase 3 SAPPHIRE study, pts with advanced non-squamous (adv nsq) NSCLC (excluding EGFR, ROS1, or ALK alterations) who initially benefited from CPI with/after platinum-based chemotherapy (≥4 months [mos] on CPI without progression) with subsequent disease progression were randomized 1:1 to sitra (100 mg QD orally) plus nivo (240 mg Q2W or 480 mg Q4W IV) [sitra/nivo] or docetaxel monotherapy (doce; 75 mg/m² Q3W IV). The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS); all by blinded independent central review, and safety.

Results

As of 20 March 2023 (median follow-up, 17.1 mos), 577 pts received sitra/nivo (n=284) or doce (n=293). Median OS was not significantly improved by sitra/nivo vs doce (12.2 vs 10.6 mos; HR 0.86 [95% CI, 0.70–1.05]; p=0.144). HR for PFS was 1.08 (95% CI, 0.89–1.32; p=0.452); median PFS for sitra/nivo vs doce was 4.4 vs 5.4 mos. ORR was 15.6% with sitra/nivo vs 17.2% with doce (p=0.597); CBR was 75.5% (sitra/nivo) vs 64.5% (doce; p=0.004). Most common (≥25%) any grade treatment-related adverse events with sitra/nivo were diarrhea (56.2% [7.5% gr ≥3]), nausea (31.3% [1.4%]), decreased appetite (28.5% [1.8%]), hypothyroidism (28.1% [0.4%]), and fatigue (26.3% [6.8%]); and diarrhea (35.5% [3.3%]), fatigue (35.5% [8.4%]), nausea (32.2% [2.6%]), decreased neutrophil count (31.9% [29.3%]), alopecia (30.8% [0.4%]), and neutropenia (26.0% [23.1%]) with doce.

Conclusions

The primary endpoint of OS was not met in pts with previously treated adv nsq NSCLC. Safety profiles for sitra/nivo and doce were consistent with prior reports for each regimen.

Clinical trial identification

NCT03906071.

Editorial acknowledgement

Medical writing support for the development of this abstract, was provided by Tamsyn Mamotte, MSc, of Ashfield MedComms, an Inizio company, and funded by Mirati Therapeutics, Inc.

Legal entity responsible for the study

Mirati Therapeutics, Inc.

Funding

Mirati Therapeutics, Inc. and Bristol Myers Squibb.

Disclosure

H. Borghaei: Financial Interests, Personal, Invited Speaker: Amgen, Pfizer, Daiichi Sankyo, Regeneron; Non-Financial Interests, Personal, Writing Engagement: Amgen, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, Beigene, iTEO, Jazz, Janssen, Da Volterra, Pum; Financial Interests, Personal, Full or part-time Employment: Fox Chase Cancer Center; Financial Interests, Personal, Stocks/Shares: Sonnetbio (Stock Options); Inspirna (formerly Rgenix, Stock Options); Nucleai (stock options); Financial Interests, Institutional, Research Grant: BMS, Lilly ; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Mirati, BMS; Financial Interests, Personal, Other, DSMB: University of Pennsylvania: CAR T Program, Takeda, Incyte, Novartis, Springworks; Financial Interests, Personal, Other, Travel: Amgen, BMS, Merck, Lilly, EMD-Serono, Genentech, Regeneron. M.L. Johnson: Financial Interests, Institutional, Research Funding: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Chec; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech / Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immun. E.B. Garon: Financial Interests, Institutional, Research Grant: ABL-Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Inc., Neon, Novartis; Financial Interests, Institutional, Advisory Role: AbbVie, ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GSK, Ipsen, Merck, Natera, Novatis, Personalis, Regeneron, Sanofi, Shionogi, Xilo. K. He: Financial Interests, Personal, Advisory Board: Mirati Therapeutics, Inc., Perthera, Bristol Myers Squibb, Iovance Biotherapeutics, Lyell, AstraZeneca, OncoC4, Beigene. D. Planchard: Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, priME Oncology, Peer CME, Samsung, AbbVie, Janssen, GSK, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, AbbVie, Sanofi-aventis, GSK, Seagen, Pierre Fabre, Gilead; Financial Interests, Personal, Principal Investigator: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi- Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie, GSK. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GSK, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche; Financial Interests, Personal, Other, DSMB: Daiichi Sankyo, Sanofi. S. Popat: Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche ; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, Blueprint, Guardant Health, Beigene, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Non-Financial Interests, Personal, Officer: European Society of Medical Oncology; Non-Financial Interests, Personal, Member of Board of Directors: Mesothelioma Applied Research Foundation; Financial Interests, Institutional, Research Grant: Guardant Health ; Non-Financial Interests, Personal, Advisory Role: International Association for the Study of Lung Cancer, ALK Positive UK, Ruth StraussFoundation, Lung Cancer Europe; Non-Financial Interests, Personal, Leadership Role: British Thoracic Oncology Group, European Thoracic Oncology Platform; Financial Interests, Personal, Other: Journal Deputy Editor, Lung Cancer: Elsevier; Sub- Investigator: Amgen, MSD, Blueprint. R.S. Herbst: Financial Interests, Personal, Other, Consulting: DynamiCure Biotechnology, eFFECTOR Therapeutics, Inc, Eli Lilly and Company, Genentech, Gilead, HiberCell, Inc., Janssen, Johnson and Johnson, Loxo Oncology, Merck and Company, Mirati Therapeutics, NextCure, Novartis, Oncocyte Corp, Oncternal Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca, Bolt Therapeutics, Bristol-Myers Squibb, Candel Therapeutics, Cybrexa Therapeutics, EMD Serono, I-Mab Biopharma, Immune-Onc Therapeutics, Inc., Normunity, Ocean Biomedical, Inc, Revelar Biotherapeutics, Inc, Ribbon Therapeutics, Xencor, Inc; Financial Interests, Personal, Member of Board of Directors: Junshi Pharmaceuticals, AACR, Immunocore, IASLC, SITC, Southwest Oncology Group; Financial Interests, Personal, Full or part-time Employment: Yale Cancer Center; Financial Interests, Personal, Stocks/Shares: Immunocore, Checkpoint Therapeutics; Financial Interests, Institutional, Other, Research support: AstraZeneca, Eli Lilly and Company, Genentech/Roche, Merck and Company. T.A. Leal: Financial Interests, Personal, Advisory Board: AstraZeneca, Novocure, Takeda, Merck, Jazz Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer, Advaxis, Bayer; Financial Interests, Personal, Other, Consulting: Regeron, AstraZeneca, Eisai, Roche, Catalyst, Jazz, Amgen. D. Dumoulin: Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Principal Investigator: BMS, Roche, Mirati, MSD; Non-Financial Interests, Personal, Advisory Role: Amgen, BMS, MSD. F. de Marinis: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Bristol Myers Squibb, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Bristol Myers Squibb, Novartis. C.H. Reynolds: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Gilead. R.L. Shazer: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics, Inc.. X. Yan: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics, Inc.. R. Harrigan: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.. S. Peters: Financial Interests, Institutional, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GSK, Illumina, Imedex, Ipsen, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Advisory Role: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, BerGenBio, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol- Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Me; Financial Interests, Institutional, Member of Board of Directors: Galenica; Financial Interests, Institutional, Principal Investigator: Amgen, Arcus, AstraZeneca, Beigene, Bristol-Myers Squibb, GSK, iTeos, Merck Sharp and Dohme, Mirati, Pharma Mar, Promontory Therapeutics, Roche/Genentech, Seattle Genetics; Financial Interests, Personal, Member: ESMO, ASCO, AACR, IASLC, SSOM, SAKK, ETOP; Financial Interests, Personal, Leadership Role: Vice President Swiss Cancer League, past President ESMO, Strategic Advisory board SPCC (Paris Saclay) Chair, ETOP scientific chair. All other authors have declared no conflicts of interest.