Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy

Abstract Background MBG453 and spartalizumab are humanized IgG4 mAbs that block binding of TIM-3 to PtdSer and PD-1 to PD-L1/2, respectively. In Ph I dose escalation, MBG453 + spartalizumab showed preliminary antitumor activity in advanced solid tumors. Here we report Ph II MBG453 + spartalizumab dose expansion in pts with NSCLC and melanoma (NCT02608268). Methods Pts with melanoma or NSCLC who had progressive disease (PD) on/after anti–PD-1/L1 therapy received MBG453 (800 mg, Q4W) + spartalizumab (400 mg, Q4W) until unacceptable toxicity, PD, or investigator/pt decision. On prior anti–PD-1/L1 therapy clinical benefit (CB) was defined as durable (DCB) if pts had a complete or partial response, or stable disease (SD) for ≥6 months, or non-durable (NDCB) if pts had SD for Results As of Feb 15, 2019, 33 pts received MBG453 + spartalizumab (melanoma: n = 16; NSCLC: n = 17); 5 (15.2%) pts were ongoing (melanoma: n = 3 [18.8%]; NSCLC: n = 2 [11.8%]); 28 (84.8%) pts discontinued, mainly due to PD (60.6%) and death due to underlying disease (12.1%). Anti–PD-1/L1 was the last therapy before enrollment in 21 (63.6%) pts (melanoma: n = 10 [62.5%]; NSCLC: n = 11 [64.7%]). On prior anti–PD-1/L1 therapy, 6 (37.5%) melanoma and 7 (41.2%) NSCLC pts had DCB and 10 (62.5%) melanoma and 9 (52.9%) NSCLC pts had NDCB; CB was unknown (UNK) in 1 NSCLC pt. On MBG453 + spartalizumab, 3/16 (18.8%) melanoma pts (prior anti-PD-1/L1: DCB n = 2; NDCB n = 1) and 7/17 (41.2%) NSCLC pts (prior anti-PD-1/L1: DCB n = 3; NDCB n = 3; UNK n = 1) had SD per RECIST 1.1. Baseline tumor PD-L1 appears higher in pts with SD vs PD. Data suggest a trend of inverse association between tumor reduction and CD163 tumor expression. Common treatment-related adverse events (TRAEs) were fatigue, nausea, and pruritus (n = 3 each [9.1%]); 0 melanoma and 2 (11.8%) NSCLC pts (pruritus, amylase, lipase, and increased ALT) had Grade 3/4 TRAEs. Conclusions MBG453 (800 mg, Q4W) + spartalizumab (400 mg, Q4W) was well tolerated but with limited efficacy in pts with melanoma and NSCLC who had PD on/after prior anti–PD-1/L1 therapy. Further evaluation of MBG453 in other indications/combinations is needed to assess the clinical relevance of TIM-3 inhibition. Editorial acknowledgement Jenny Winstanley, PhD, of Articulate Science Ltd. Legal entity responsible for the study Novartis Pharmaceuticals. Funding Novartis Pharmaceuticals. Disclosure G. Curigliano: Honoraria (self), Advisory Board: Novartis; Honoraria (self), Advisory Board: Roche; Speaker Bureau / Expert testimony, Expert talk: Pfizer; Speaker Bureau / Expert testimony, Expert talk: Eli Lilly; Advisory / Consultancy, Scientific consultation: Ellipsis. A. Santoro: Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: AbbVie; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Advisory / Consultancy, Speaker Bureau / Expert testimony: Gilead; Speaker Bureau / Expert testimony: AstraZencea; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Arquile; Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Sandoz; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD. D. Kim: Research grant / Funding (institution): Alpha Biopharm; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Hanmi; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): ONO Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): TP Therapeutics; Research grant / Funding (institution): Xcovery; Research grant / Funding (institution): Yuhan. S. Hodi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol Mysers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Takeda; Advisory / Consultancy: Surface; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Compass Therapeutics; Advisory / Consultancy: Apricity; Advisory / Consultancy: Bayer; Advisory / Consultancy: Aduro; Advisory / Consultancy: Partners Therapeutics; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Pionyr; Advisory / Consultancy: 7 Hills Pharma; Advisory / Consultancy: Verastem; Advisory / Consultancy: Torque; Advisory / Consultancy: Rheos. T. Doi: Research grant / Funding (institution): Lilly ; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Boehringer Ingelheim ; Research grant / Funding (institution): Quintiles; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Dainippon Sumitomo; Research grant / Funding (institution): Kyowa Hakko Kirin; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Otsuka. T. Longmire: Full / Part-time employment: Novartis. H. Sun: Full / Part-time employment: Novartis. A. Xyrafas: Full / Part-time employment: Novartis. S. Gutzwiller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. L. Manenti: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. All other authors have declared no conflicts of interest.