Immune checkpoint inhibitor Bavencio (avelumab) has an acceptable safety profile and shows some anti-tumor activity among heavily pretreated ovarian cancer patients, according to a Phase 1b trial.
Findings from the trial were reported in the study, “Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer,” published in the journal JAMA Oncology.
While platinum-based chemotherapy, alone or in combination with other treatments, is the current standard of care for advanced ovarian cancer patients, about 70 percent will see their disease return or progress within three years.
Patients who fail platinum chemotherapy have poor outcomes, with current approaches providing limited benefits. As a result, additional treatments are needed to prolong survival in these patients.
The interaction between PD-L1 and its receptor PD-1, found in immune cells, is used to prevent overactive immune responses that might damage the organism. However, tumor cells hijack this mechanism to prevent immune attacks.
Molecules that prevent this binding are called immune checkpoint inhibitors. Increasing evidence indicates that these therapies could be beneficial to ovarian cancer patients. In fact, the presence of immune cells inside tumors seems to predict better outcomes, and most tumors produce the PD-L1 factor.
Several immune checkpoint inhibitors are already approved as cancer treatments. Bavencio, however, seems to induce a broader immune activation than other molecules of the same kind.
The therapy, produced by Merck KGaA (known as EMD Serono in the U.S. and Canada) and Pfizer, is already approved for metastatic Merkel cell carcinoma and for advanced urothelial cancer.
The Phase 1 trial (NCT01772004), called JAVELIN Solid Tumor, was designed to study the safety and efficacy of Bavencio across multiple cancer types. In the first part, patients received ascending doses of the treatment to determine a safe dose with the best efficacy. The selected dose was then tested across several expansion groups.
The ovarian cancer group included 125 women, at a median age of 62 years, who had received at least one chemotherapy regimen, including a platinum agent. Patients had received a median of three prior lines of treatment for their advanced disease, and 42.4% had received four or more therapies.
In the trial, patients received Bavencio every two weeks until their disease progressed, they experienced unacceptable signs of toxicity, or they withdrew from the study. Patients received a median of six infusions in all and were followed for a median of 26.6 months.
A response to treatment was seen in 9.6% of patients, including one (0.8%) complete response. Responses lasted for a median of 10.4 months. Another 42.4% of patients had disease stabilization, amounting to a disease control rate of 52%.
The median time patients lived without disease progression was 2.6 months. At one year, 10.2% of patients were alive and progression-free. Patients lived for a median of 11.2 months.
Responses and survival outcomes were better particularly for patients who had only received one prior line of therapy, and for those who had first responded to a platinum-based chemotherapy. Interestingly, patients responded to Bavencio regardless of their PD-L1 and BRCA mutational status.
A total of 68.8% of patients experienced a treatment-related adverse event. The most frequent were infusion-related reactions, fatigue, diarrhea, and nausea. Addditionally, 33.6% of patients had a serious adverse event, 2.4% of which were deemed treatment-related.
Bavencio showed “antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer,” the researchers wrote.
While these results support the anti-tumor activity of Bavencio, two recent Phase 3 trials testing Bavencio in combination with and/or after platinum-based chemotherapy — the JAVELIN Ovarian 100 (NCT02718417) — or alone or in combination with pegylated liposomal doxorubicin — the JAVELIN Ovarian 200 (NCT02580058) — showed that Bavencio had no added benefit.
Another Phase 3 trial in ovarian cancer patients — called JAVELIN Ovarian PARP 100 trial (NCT03642132) — is testing a combination of Bavencio plus the PARP inhibitor Talzenna (talazoparib) as a maintenance treatment after surgery and chemotherapy.