Avelumab Misses Primary Endpoints in Phase III Ovarian Cancer Trial

Avelumab (Bavencio) alone or in combination with pegylated liposomal doxorubicin (PLD) did not induce a statistically significant improvement in overall survival (OS) or progression-free survival (PFS) versus PLD alone in patients with platinum—resistant/refractory ovarian cancer, missing the primary endpoints of the phase III JAVELIN Ovarian 200 trial.

Merck KGaA and Pfizer, the developers of the PD-L1 inhibitor, reported in a press release that avelumab plus PLD led to an HR for PFS of 0.78, which did not meet the prespecified criteria for superiority (repeated confidence interval [RCI], 0.587-1.244; one-sided P value = .0301). The OS endpoint with the avelumab combination was also not met (HR, 0.89; RCI, 0.744-1.241; one-sided P value = .2082).

Avelumab monotherapy also missed the PFS endpoint (HR, 1.68; RCI, 1.320-2.601; one-sided P value >.99) and OS endpoint (HR, 1.14; RCI, 0.948-1.580; one-sided P value = .8253). Merck and Pfizer noted that these data are currently being analyzed, and detailed results will be presented at a later date.

“Effective management of platinum-resistant or -refractory ovarian cancer remains the biggest unmet medical need facing women with recurrent ovarian cancer today. The current treatment options have only limited and short-lived efficacy for the majority of women, as evidenced by an average life expectancy that does not exceed one year for this group,” Eric Pujade-Lauraine, MD, PhD, head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, said in a statement.

“As a researcher and clinician, I know how important it is to continue to improve the outlook for women with advanced ovarian cancer and look forward to the results of more trials exploring the role of avelumab in delaying recurrence in platinum-sensitive patients and earlier lines of therapy,” added Pujade-Lauraine.

In the multicenter, randomized, phase III JAVELIN Ovarian 200 trial (NCT02580058), 556 patients with platinum-resistant or -refractory ovarian cancer were randomized to receive either avelumab intravenously (IV) at 10 mg/kg every 2 weeks in 4-week cycles, avelumab IV at 10 mg/kg every 2 weeks in 4-week cycles plus PLD at 40 mg/m² IV every 4 weeks in 4-week cycles, or PLD at 40 mg/m² IV every 4 weeks in 4-week cycles.

Patients had histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, platinum-resistant/-refractory disease, previously received up to 3 lines of systemic therapy, and measurable disease. The primary endpoints were superior OS or PFS for one or both avelumab arms versus PLD; objective response rate (ORR) was a secondary endpoint.

The ORR was 13.3% (95% CI, 8.8%-19.0%) for avelumab combined with PLD, 3.7% (95% CI, 1.5%-7.5%) for single-agent avelumab, and 4.2% (95% CI, 1.8%-8.1%) for PLD alone.

The companies noted that there were no new safety signals reported with either avelumab monotherapy or with the combination, and the safety profile of avelumab in this trial was consistent with that observed in the overall JAVELIN clinical development program.

“JAVELIN Ovarian 200 enrolled a high proportion of patients with aggressive, refractory disease that had no response to prior platinum-based chemotherapy, a population known to have disease that is challenging to treat; as such, this group of patients is typically not included in phase III ovarian cancer trials,” Chris Boshoff, MD, PhD, senior vice president, head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development, said in the news release.

“We initiated the JAVELIN Ovarian 200 trial as the first phase III study of a checkpoint inhibitor in the platinum-resistant or -refractory setting recognizing these patients have the most pressing need for new treatment options. The results speak to the significant challenges these women face,” added Boshoff.

The ongoing, international, multicenter, open-label, randomized JAVELIN Ovarian 100 trial (NCT02718417) is evaluating avelumab in combination with and/or following platinum-based chemotherapy in treatment-naïve patients with locally advanced or metastatic epithelial ovarian cancer.

Moreover, JAVELIN Ovarian PARP 100 (NCT03642132) is an open-label, multicenter, phase III study randomizing patients with previously untreated advanced ovarian cancer to avelumab plus platinum-based chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib (Talzenna); chemotherapy followed by maintenance therapy with talazoparib; or chemotherapy plus bevacizumab (Avastin), followed by bevacizumab maintenance.

Merck KGaA, Darmstadt, Germany, and Pfizer Provide Update on Avelumab in Platinum-Resistant/Refractory Ovarian Cancer. Merck KGaA and Pfizer. Published November 19, 2018.. Accessed November 19, 2018. https://bit.ly/2PGGzPB.