3721 - Phase 1 study results from an esophageal squamous cell carcinoma (ESCC) cohort treated with M7824 (MSB0011359C), a bifunctional fusion protein targeting transforming growth factor _ (TGF-_) and PD-L1

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.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA.

Editorial Acknowledgement

Medical writing support was provided by ClinicalThinking, and was funded by Merck KGaA, Darmstadt, Germany.

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.