Avelumab Falls Short in Phase III Gastric Cancer Trial

Chris Boshoff, MD, PhD

Avelumab (Bavencio) did not improve overall survival (OS) compared with chemotherapy in previously treated patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to findings from the phase III JAVELIN Gastric 300 trial.

The findings were announced by Merck KGaA and Pfizer, the co-developers of the anti—PD-L1 agent. The companies reported that results from the study will be shared at an upcoming medical meeting.

"Gastric cancer in the third-line setting is a particularly hard-to-treat and heterogeneous disease, and importantly, this was the first trial conducted with a checkpoint inhibitor compared to an active chemotherapy comparator rather than placebo in a global patient population," Luciano Rossetti, MD, executive vice president, global head of Research & Development at the Biopharma business of Merck, said in a press release.

"Data from this study will provide valuable information for physicians treating this late stage disease. We remain committed to our ongoing gastric cancer program with avelumab including the JAVELIN Gastric 100 study in the first-line switch maintenance setting," added Rossetti.

The multicenter, international, randomized, open-label JAVELIN Gastric 300 trial randomized 371 patients with unresectable, recurrent or metastatic gastric or GEJ adenocarcinoma whose disease progressed following 2 prior therapeutic regimens. Patients were randomized to best supportive care plus either avelumab or physician's choice of paclitaxel or irinotecan monotherapy. The study was conducted at 147 sites in Asia, Australia, Europe, North America, and South America.

OS was the primary endpoint of the trial. There were no new safety signals identified, and the safety profile with avelumab was consistent with previously reported study findings.

Avelumab had previously demonstrated promising activity in gastric cancer in results presented at the 2016 Gastrointestinal Cancers Symposium. The data included patients with unresectable gastric or GEJ cancer who were receiving avelumab as a second-line or maintenance therapy.

Among 55 patients who received avelumab maintenance after first-line chemotherapy in the phase Ib study, 1 had a complete response and 3 others had partial responses, for an overall response rate (ORR) of 7.3%. In the second-line setting, avelumab demonstrated an ORR of 15%. Stable disease rates were 35% in the second-line setting and 47.3% in the maintenance cohort.

The phase Ib trial focused on patients whose disease progressed after first-line chemotherapy (n = 20) or those who did not have disease progression during first-line therapy (n = 55). In both cohorts, avelumab was administered at 10 mg/kg every 2 weeks.

Avelumab led to a partial response in 3 patients and stable disease in 7 others in the second-line cohort, resulting in a disease control rate of 50%. In the maintenance cohort, 4 patients had partial responses and 26 had stable disease for a disease control rate of 54.5%.

Nine patients (4 second-line, 5 maintenance) had tumor shrinkage >30%. These responses included 2 patients who had HER2-positive disease and 2 others with stable disease who did not qualify for response because of the appearance of a new lesion on subsequent scans.

The second-line cohort had a median progression-free survival (PFS) of 11.6 weeks. At 24 weeks, 19.3% of patients remained progression free and alive. The maintenance cohort had a median PFS of 14.1 weeks and a 24-week PFS rate of 34.0%.

With respect to safety, 47 of the 75 patients (63%) in both cohorts had treatment-emergent adverse events. The most frequently reported adverse events (all grades) were infusion-related reactions (16%), nausea (9.3%), elevated liver enzymes (9.3% each for AST and ALT), fatigue (8%), vomiting (8%), chills (8%), and pruritus (8%). The only grade 3/4 adverse event that occurred in more than one patient was fatigue (two patients, 2.7%).

"Gastric cancer is a leading cause of cancer death globally with clear unmet needs, and the results provide important insights as we continue to investigate the role of avelumab for the treatment of gastric cancer," Chris Boshoff, MD, PhD, senior vice president and head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development, said in a press release.

Avelumab currently has FDA approved indications for urothelial carcinoma and Merkel cell carcinoma.

Chung HC, Arkenau H-T, Wyrwicz L, et al. Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with advanced gastric or gastroesophageal junction cancer. J Clin Oncol. 2016;34 (suppl 4S; abstr 167).