Sabatolimab in combination with spartalizumab in patients with non-small cell lung cancer or melanoma who received prior treatment with anti-PD-1/PD-L1 therapy: a phase 2 multicentre study.

Objective: This study evaluates the safety/efficacy of sabatolimab plus spartalizumab in patients with melanoma or non-small cell lung cancer (NSCLC).
Design, Setting and Participants: This is a phase 1-1b/2, open-label, multinational, multicentre study of patients with advanced/metastatic melanoma or NSCLC with ≥1 measurable lesion.
Interventions: Patients were given sabatolimab 800 mg every 4 weeks plus spartalizumab 400 mg every 4 weeks until unacceptable toxicity, disease progression and/or treatment discontinuation.
Outcome Measures: The phase 2 primary outcome measure was overall response rate and secondary objectives included evaluation of the safety, tolerability, efficacy and pharmacokinetics of sabatolimab in combination with spartalizumab.
Results: 33 patients (melanoma n=16, NSCLC n=17) received sabatolimab plus spartalizumab. 31 (94%) experienced ≥1 adverse event (AE); 15 (46%) experienced grade 3/4 events. The most frequent grade ≥3 AEs for NSCLC were anaemia, dyspnoea and pneumonia (each n=2, 12%); for patients with melanoma, the most frequent grade ≥3 AEs were physical health deterioration, hypokalaemia, hypophosphataemia, pathological fracture and tumour invasion (each n=1; 6%). One (3%) patient discontinued treatment due to AE. Stable disease was seen in three patients with melanoma (19%) and six patients with NSCLC (35%). Median progression-free survival was 1.8 (90% CI 1.7 to 1.9) and 1.7 (90% CI 1.1 to 3.4) months for patients with melanoma and NSCLC, respectively. Patients with stable disease had higher expression levels of CD8, LAG3, programmed death-ligand 1 and anti-T-cell immunoglobulin and mucin-domain containing-3 at baseline. The pharmacokinetics profile of sabatolimab was consistent with the phase 1 study.
Conclusions: Sabatolimab plus spartalizumab was well tolerated in patients with advanced/metastatic melanoma or NSCLC who had progressed following antiprogrammed death-1/antiprogrammed death-ligand 1 treatment. Limited antitumour activity was observed. The tolerability of sabatolimab administration supports the potential to explore treatment with sabatolimab in various combination regimens and across a spectrum of tumour types.
Trial Registration Number: NCT02608268.
Competing Interests: Competing interests: NM is the founder of and owns shares in MaxiVAX SA and is the CSO at MaxiVAX. C-CL reports an advisory role for AbbVie, Bayer, Blueprint Medicines, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Novartis and PharmaEngine; honoraria from Lilly, Novartis and Roche; and travel support from BeiGene, Daiichi Sankyo and Lilly. GC reports research funding from Merck and fees for advisory board from BMS, Merck, AstraZeneca, Novartis, Lilly, Pfizer, Roche, Exact Science, Daiichi Sankyo, GSK, Sanofi and Seagen. AS reports serving on an advisory board for BMS, Servier, Gilead, Pfizer, Eisai, Bayer and MSD (Merck Sharp & Dohme); consultancy for Arqule, Sanofi and Incyte; and participating in speaker’s bureaus for Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer and MSD. D-WK reports research funding to his institution from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, and GSK; and travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi-Sankyo. DT reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Ipsen, Eisai and BMS; and consulting fees from Novartis, BMS and MSD. FSH reports receiving personal fees for serving on an advisory board for Surface, Compass Therapeutics, Apricity, Pionyr, 7 Hills Pharma, Torque, Bicara, Checkpoint Therapeutics, Bioentre, Iovance, Trillium, Amgen and Rheos; consultancy for Bristol-Myers Squibb, Merck, EMD Serono, Novartis, Sanofi, Pieris, Genentech/Roche, Catalym, Immunocore, Kairos, Eisai and Zumutor; serving as an advisor consultant for Aduro; and receiving other personal fees from Gossamer. FSH reports receiving grant support to institution from Bristol-Myers Squibb and Novartis; and having equity in Apricity, Pionyr, Torque, Bicara and Checkpoint Therapeutics. FSH holds issued patents #7250291, #9402905, #10279021 and #10106611 and pending patents #20100111973 (with royalties), #20170248603, #20160340407, #20160046716, #20140004112, #20170022275, #20170008962 and #20170343552, as well as a pending patent for Methods of Using Pembrolizumab and Trebananib. SW reports serving on an advisory board for Eisai, Bristol-Myers Squibb and Pierre Fabre (paid to institution). TD reports receiving grant support to institution from Lilly, MSD, Daiichi-Sankyo, Sumitomo Dainippon, Taiho, Novartis, Merck Biopharma, Janssen Pharma, Pfizer, BMS, AbbVie, Eisai, IQVIA, Chugai Pharma; consulting fees from Sumitomo Dainippon, Taiho, Takeda, Chugai Pharma, AbbVie, Bayer, Rakuten Medical, Otsuka Pharma, KAKEN Pharma, KYOWA KIRIN, SHIONOGI, PRA Health Science; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Rakuten Medical, Ono Pharma, Daiichi-Sankyo, AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for MSD, Daiichi-Sankyo, Amgen, Novartis, Boehringer Ingelheim, Janssen Pharma, AbbVie, Bayer, Astellas Pharma. CS-P was an employee of Novartis Institutes for BioMedical Research and holds patents on TIM-3 through Harvard/BWH and CoStim/Novartis. CS-P is employed by and has options in Larkspur Biosciences. SS is an employee of Novartis Institutes for BioMedical Research. SC is an NIBR employee and holds NVS stocks. AX has nothing to disclose. SG is an employee of Novartis Institutes for BioMedical Research. AP is an employee of Novartis Institutes for BioMedical Research.
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