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Phase I study results from an esophageal squamous cell carcinoma (ESCC) cohort treated with M7824 (MSB0011359C), a bifunctional fusion protein targeting transforming growth factor β (TGF-β) and PD-L1

2018; Elsevier BV; Volume: 29; Linguagem: Inglês

10.1093/annonc/mdy282.026

1569-8041

C.-C. Lin, Toshihiko Doi, Kei Muro, Ming Hou, Taito Esaki, Hiroki Hara, H.C. Chung, Mitsumasa Osada, Christoph Helwig, Shunsuke Kondo,

Cancer Immunotherapy and Biomarkers

Background: Inhibition of the TGF-β pathway, which promotes tumor immunosuppression, may enhance the clinical response to PD-(L)1 monoclonal antibodies (mAbs). M7824 is an innovative first-in-class bifunctional fusion protein composed of a human anti–PD-L1 IgG1 mAb fused with 2 extracellular domains of the TGFβ receptor II to function as a TGF-β "trap". We report on the safety and efficacy of M7824 in a cohort of Asian patients (pts) with ESCC. Esophageal cancer is the sixth most common type of cancer in Eastern Asia, with ESCC accounting for ≈90% of cases. ESCC represents an area of high unmet need. Additionally, no immunotherapies have been yet approved for this patient population, and monochemotherapy with a taxane or irinotecan remains the 2L standard of care (ORRs, ≤16%). Methods: In this expansion cohort of the ongoing, phase 1 trial NCT02699515, Asian pts with ESCC unselected for PD-L1 expression, for which no standard therapy exists or has failed, received M7824 1,200 mg q2w until disease progression, unacceptable toxicity, or trial withdrawal. The primary objective is safety and tolerability; secondary objectives include best overall response per RECIST v1.1. Results: As of January 4, 2018, 30 pts received M7824 for a median of 6.1 (range, 2.0–44.1) weeks; 4 pts remained on treatment. 76.7% of patients had received ≥2 prior lines of treatment. The most common TRAEs were hypothyroidism, maculopapular rash (both 16.7%), rash (13.3%), and interstitial lung disease (ILD; 10.0%). Grade 3 TRAEs occurred in 4 pts (13.3%; eczema, increased amylase, lip SCC, maculopapular rash, rash); 2 grade 4 TRAEs were observed (6.7%; ILD, increased blood creatine phosphokinase). 3 treatment discontinuations, but no deaths, due to TRAEs occurred. 6 pts (confirmed ORR, 20.0%; unconfirmed ORR, 26.7%) had a partial response (duration of response, 1.4+, 2.8+, 4.2+, 4.2+, 5.8, and 7.0 months); 5 pts had stable disease (disease control rate, 36.7%) by investigator read. Conclusions: M7824 had a manageable safety profile and promising preliminary efficacy in heavily pretreated Asian pts with ESCC and no/limited treatment options. Clinical trial identification: NCT02699515. Editorial acknowledgement: Medical writing support was provided by ClinicalThinking, and was funded by Merck KGaA, Darmstadt, Germany. Legal entity responsible for the study: Merck KGaA, Darmstadt, Germany. Funding: Merck KGaA. Disclosure: T. Doi: Consultancy: Lilly Japan, Chugai Pharma, Kyowa Hakko Kirin, Merck Sharp and Dohme Corp, Daiichi Sankyo, Amgen, Sumitomo Dainippon, Taiho Pharmaceutical; Research funding: Taiho Pharmaceutical, Novartis, Merck Serono, Astellas Pharma, Merck Sharp and Dohme Corp, Janssen, Boehringer Ingelheim, Takeda, Pfizer, Lilly Japan, Sumitomo Group, Chugai Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Celgene, Bristol-Myers Squibb, Abbvie Quintiles. M-M. Hou: Employee: Chang Gung Memorial Hospital. H. Hara: Honoraria: Chugai Pharma, Taiho Pharmaceutical, Merck Serono, Yakult Honsha, Lilly, Ono Pharmaceutical, Takeda; Consulting or advisory role: Ono Pharmaceutical, Chugai Pharma, Merck Serono, Merck Sharp & Dohme Corp; Research funding: AstraZeneca, Chugai Pharma, Merck Serono, Merck Sharp & Dohme Corp, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Boehringer Ingelheim, Dainippon Sumitomo Pharma, Daiichi Sankyo, Lilly, Pfizer, LSK BioPharma, Eisai, Incyte. H-C. Chung: Employee: Yonsei University College of Medicine; Consultancy: Taiho, Celltrion, Merck Sharp and Dohme Corp, Lilly, Quintiles, Bristol-Myers Squibb, Merck-Serono; Research funding: Lilly, GlaxoSmithKline, Merck Sharp and Dohme Corp, Merck-Serono, Bristol-Myers Squibb/Ono, Taiho; Speakers bureau: Merck-Serono, Lilly, Foundation Medicine. M. Osada: Employee: Merck Serono. C. Helwig: Employee: Merck KGaA. All other authors have declared no conflicts of interest.