Late-breaking and press abstracts
LBA15 - A Phase 1B Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Advanced Gastric Cancer

https://doi.org/10.1093/annonc/mdu438.15Get rights and content
Under an Elsevier user license
open archive

ABSTRACT

Aim: The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. Pembro is a highly selective, humanized IgG4/kappa isotype monoclonal antibody designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, thus reactivating the immune system to eradicate the host tumor. In a phase 1b study (Clinicaltrials.gov: NCT01848834), we assessed the safety, tolerability, and antitumor activity of pembro in gastric cancer pts.

Methods: Using a prototype immunohistochemistry assay, PD-L1 expression was assessed in archival tumor samples from pts with recurrent/metastatic adenocarcinoma of the stomach or gastroesophageal junction. Eligible pts with PD-L1 staining in stroma or ≥1% of tumor cells were enrolled and treated with pembro 10 mg/kg every 2 weeks for up to 24 months or until complete response, disease progression, or unacceptable toxicity. Enrollment was designed to include an equal number of pts from Asia Pacific (AP) and the rest of the world (ROW). Adverse events (AEs) were monitored and graded per the NCI CTCAE v4.0. Radiographic imaging was performed every 8 weeks. Primary efficacy end point was overall response rate (ORR) assessed by RECIST v1.1.

Results: Of the 162 pts screened, 65 (40%) were PD-L1+ and 39 enrolled: 19 from AP, 20 from ROW. Median age was 63 y, and 72% of pts were men. Pts from AP were more heavily pretreated than pts from ROW (≥2 prior therapies in 79% vs 55%). Median follow-up duration was ∼6 mo. The most common AEs deemed treatment related by investigators were hypothyroidism and fatigue (n = 5 each). Grade ≥3 AEs deemed treatment related occurred in 3 pts (n = 1 each for hypoxia, peripheral neuropathy, and pneumonitis). ORR (confirmed + unconfirmed) was 32% in AP and 30% in ROW. Responses were ongoing for 6/6 AP pts and 5/6 ROW pts (median response duration not reached; range 8+ to 20+ wk). Evidence of an association between PD-L1 expression and PFS (P = 0.032) and ORR (P = 0.071) was observed.

Conclusions: Pembro was generally well tolerated by and provided antitumor activity in pts with advanced gastric cancer that expressed PD-L1. The robust antitumor activity observed supports the further development of pembro in advanced gastric cancer.

Disclosure: E.J. Gonzalez: Is employee of and holds stock in Merck & Co., Inc.; J. Pulini: Is former employee of Merck & Co., Inc.; A.B. Ray, M. Dolled-Filhart, K. Emancipator, K. Pathiraja, X. Shu and M.R. Koshiji: Is an employee of Merck & Co., Inc.; J. Cheng: Is an employee of and holds stock in Merck & Co., Inc. All other authors have declared no conflicts of interest.

Cited by (0)