Abstract 994P
Background
Capmatinib (cap) is a selective MET inhibitor approved for patients (pts) with advanced NSCLC (aNSCLC) harboring MET exon 14 skipping mutation (METex14) showing ORR [95% CI] of 66.7% [53.3, 78.3] in treatment (tx)-naïve pts. Spartalizumab (sparta) is a monoclonal antibody targeting programmed death protein-1 (PD-1). Cap enhances T cell mediated antitumor response in mice treated with PD-1 inhibitors. Combining cap with sparta may be beneficial in aNSCLC pts with METex14.
Methods
This phase II study consisted of 2 parts: open-label, single-arm run-in part, where pts received cap 400 mg orally BID + sparta 400 mg i.v Q4W followed by randomized, double-blind, placebo-controlled part to evaluate the efficacy and safety of cap+sparta vs cap+placebo. Tx-naïve aNSCLC pts with METex14 and without ALK or EGFR alterations were included. The primary endpoint was investigator-assessed ORR as per RECIST v1.1. Herein, we report data from the run-in part.
Results
At data cut-off (DCO) of Feb 01, 2022, 31 pts were included in the run-in part; median age: 73 (range: 52-89) years; females (51.6%) and ECOG PS of 0/1 in 38.7%/61.3% of pts. The ORR [95% CI] was 38.7% [21.8, 57.8] and DCR [95% CI] was 77.4% [58.9, 90.4]. Median DOR has not been reached. Median PFS [95% CI] is 13.3 months [9.3, NA] but data remains to mature further. The preliminary PK results of both drugs showed consistency with prior monotherapy studies. Most common Tx-related AEs (any grades [GR], ≥30%) were peripheral edema (71%), elevated serum creatinine (45.2%), elevated ALT and AST (35.5% each). No Tx-related GR 3/4 pneumonitis and no fatal toxicity has been reported. Higher rates of tx-related AEs leading to dose reduction/interruption (80.6%) and/or discontinuation (35.5%) were seen with cap+sparta regimen vs other cap monotherapy studies, suggesting poor tolerability to the combination. Thus, study enrollment was halted, and all ongoing pts were discontinued from sparta. At DCO, 15 pts remain on cap monotherapy.
Conclusions
The addition of sparta to cap treatment was not well tolerated and resulted in modest antitumor activity when compared with data from other cap monotherapy studies in tx-naïve aNSCLC pts with METex14.
Clinical trial identification
NCT04323436.
Editorial acknowledgement
Editorial assistance was provided by Apra Manral (Novartis Healthcare Pvt. Ltd.).
Legal entity responsible for the study
Novartis Pharma AG.
Funding
Novartis Pharma AG.
Disclosure
J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. R. Heist: Financial Interests, Personal, Advisory Board: Daichii Sankyo, Novartis, EMD Serono; Financial Interests, Personal, Invited Speaker: Chugai Roche; Financial Interests, Personal, Other, review of cancer histories: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, consulting honoraria: AbbVie; Financial Interests, Institutional, Invited Speaker: Daichii Sankyo, Novartis, AbbVie, Roche, Incyte, Mirati, Agios, Corvus, Turning Point, Lilly, Exelixis; Non-Financial Interests, Member: IASLC, ASCO, AACR. T.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Janssen, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Principal Investigator: AstraZeneca/MedImmune, Boryung, Hanmi, Janssen, Boehringer Ingelheim, Novartis, Takeda, Sanofi, Roche/Genentech, Merck Sharp & Dohme Corp, Merck Serono, Regeneron, Genmab, Bayer. M. Nishio: Financial Interests, Personal and Institutional, Advisory Board, consulting/advisory; honoraria; research funding (institution): Ono Pharmaceuticals, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board, consulting: Daiichi Sankyo, Lilly, AstraZeneca, MSD, Takeda; Financial Interests, Personal and Institutional, Funding, honoraria; research funding (institution): Takeda, AstraZeneca, Pfizer, Novartis, Merck; Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Novartis; Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim, Nippon Kayaku; Financial Interests, Personal and Institutional, Advisory Board, honoraria; research funding (institution): Janssen; Financial Interests, Personal, Advisory Board, consulting/advisory: Teijin Pharma. R.R. Kanthala, E. Leo, E. Giorgetti, Y. Wang: Financial Interests, Personal, Full or part-time Employment: Novartis AG. F.I. Mardjuadi: Financial Interests, Personal, Full or part-time Employment: Novartis AG; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Novartis AG. A. Cortot: Financial Interests, Personal, Advisory Role, Support for attending meetings and/or travel: Novartis; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis, Astra-Zeneca, Roche, BMS, MSD, Pfizer, Takeda, Janssen; Financial Interests, Personal, Advisory Role: Astra-Zeneca, Roche; Financial Interests, Institutional, Research Grant: Roche, Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer. All other authors have declared no conflicts of interest.