KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer.

Abstract

4003 Background: Pembro has shown promising antitumor activity and manageable safety in a phase 1 study of pts with previously treated advanced gastric cancer. We conducted a global, multicohort, phase 2 study of pembro in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (KEYNOTE-059;NCT02335411). Methods: Cohort 1 enrolled 259 pts, aged ≥18 y with measurable recurrent or metastatic G/GEJ adenocarcinoma who had progressed on ≥2 prior chemotherapy regimens and had ECOG PS 0-1. Pts received pembro 200 mg Q3W up to 2 y or up to disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). Primary end points: ORR (RECIST 1.1, by central review), safety, and tolerability. Results: Of 259 pts in cohort 1, 76.4% were men; median age was 62.0 y. 51.7% and 48.3% received pembro as 3rd-line (3L) and 4L+ therapy, respectively. 57.1% had PD-L1+ tumors. At data cutoff (Oct 19, 2016), median duration of follow-up was 5.4 mo (range, 0.5 to 18.7). Overall ORR (CR + PR) was 11.2% (95% CI, 7.6-15.7); 1.9% of pts (95% CI, 0.6-4.4) had CR, 9.3% had PR (95% CI, 6.0-13.5), 17% (95% CI, 12.6-22.1) had SD, and 55.6% (95% CI, 49.3-61.7) had PD. Median DOR was 8.1 mo (range, 1.4+ to 15.1+). ORR was 14.9% (95% CI, 9.4-22.1) in 3L pts and 7.2% (95% CI, 3.3-13.2) in 4L+. In PD-L1+ pts, ORR was 15.5% (95% CI, 10.1-22.4) with 2.0% (95% CI, 0.4-5.8) CR and 13.5% (95% CI, 8.5-20.1) PR; in PD-L1– pts, ORR was 5.5% (95% CI, 2.0-11.6), with 1.8% (95% CI, 0.2-6.5) CR and 3.7% (95% CI, 1.0-9.1) PR. In 3L pts with PD-L1+ tumors, ORR was 21.3% (95% CI, 12.7-32.3), with 4.0% (95% CI, 0.8-11.2) CR; in 3L pts with PD-L1– tumors, ORR was 6.9% (95% CI, 1.9-16.7), with 3.4% (95% CI, 0.4-11.9) CR. Grade 3-5 treatment-related AEs (TRAEs) occurred in 43 pts (16.6%). TRAEs led to discontinuation in 2 pts (abnormal LFT, bile duct stenosis) and were fatal in 2 pts (acute kidney injury, pleural effusion). Conclusions: Pembro showed encouraging efficacy and manageable safety after ≥2 prior lines of therapy in pts with advanced G/GEJ cancer in this large phase 2 trial. Survival and additional biomarker data, including MSI status, will be presented. Clinical trial information: NCT02335411.

Multimodal Anti-tumor Approaches Combined with Immunotherapy to Overcome Tumor Resistance in Esophageal and Gastric Cancer

“…Based on these promising results, KEYNOTE-059 was developed as a phase II trial evaluating pembrolizumab in advanced adenocarcinoma of the gastroesophageal junction. Cohort 1 evaluated pembrolizumab as third line agent, while the agent was assessed as first line agent in recurrent or metastatic HER-2 positive and PD1 positive gastroesophageal cancer (105,106). In cohort 1, preliminary results revealed an overall response rate for patients in the third-line setting of 21.3%, and 3.4% had a complete response.…”

Current Status of Checkpoint Inhibitors in the Treatment of Esophageal and Gastric Tumors – Overview of Studies

“…Studie tedy potvrdila prediktivní význam PD-L1 exprese u nádorů žaludku. Toxicita stupně ≥ 3 se vyskytla v 16,6 % případů [11]. Součástí této studie byla také podskupina pa cientů (kohorta 2), u nichž byla léčba pembrolizumabem podávána v 1. linii spolu s cisplatinou a 5-FU, odpověď u této podskupiny byla téměř v 60 % pří-padů.…”

Checkpoint Inhibitors in the Treatment of Upper Gastrointestinal Tract Tumors

“…K objektivní odpovědi (objective response rate -ORR) došlo u 22 % pa cientů, v ně kte rých pří-padech však byl zaznamenán dlouhodobý efekt, 6měsíčního OS dosáhlo 64 % pa cientů [8]. Na studii fáze I navázala studie fáze II KEYNOTE-059 (NCT02335411), jejíž publikaci fulltextem nyní očeká-váme [9]. Jedná se o vícekohortovou studii.…”