M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in Asian patients with pretreated recurrent or refractory gastric cancer: Preliminary results from a phase I trial.

Abstract

100 Background: Inhibiting the transforming growth factor β (TGF-β) pathway, which plays a key role in tumor immunosuppression, may enhance the response to programmed death 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs). M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against PD-L1 fused with the extracellular domain of TGF-β receptor II, which serves as a TGF-β “trap.” We report preliminary results in Asian patients with heavily pretreated gastric cancer. Methods: In this expansion cohort of the ongoing, phase 1, open-label trial NCT02699515, patients with recurrent or refractory unresectable stage IV gastric or gastroesophageal junction adenocarcinoma for which no standard therapy exists or standard therapy has failed receive M7824 1200 mg q2w until confirmed progressive disease, unacceptable toxicity or trial withdrawal. The primary objective is safety; secondary objectives include best overall response (BOR) per RECIST v1.1. Results: As of 6 September 2017, 31 heavily pretreated patients with advanced gastric cancer (67.7% received ≥3 prior anticancer therapies) received M7824 for a median duration of 6.1 (range: 2-30) weeks (median number of M7824 infusions: 3 [range: 1-13]); 8 patients remained on treatment. Four patients (12.9%) experienced grade 3 treatment-related adverse events (anemia and diarrhea 1 each and 2 rash). No treatment-related grade 4 AEs occurred. One grade 5 event (total 5 doses received) was considered possibly treatment related, but suspected rupture of preexisting thoracic aortic aneurysm was cited as other probable cause by the investigator. There were 5 confirmed partial responses (4 ongoing after 4-6 months of follow-up) based on investigator assessment of BOR (overall response rate: 16.1%). This is an ongoing study; updated data will be presented. Conclusions: These preliminary data show that M7824 resulted in a manageable safety profile in heavily pretreated Asian patients with gastric cancer. Early signs of clinical efficacy are encouraging. Clinical trial information: NCT02699515.