Promising Combination Moves Into Kidney Cancer

According to findings from the phase 1b JAVELIN Renal 100 trial, the combination of Bavencio (avelumab) — a PD-L1 inhibitor – and Inlyta (axitinib) – a VEGF inhibitor – had a response rate of 58.2 percent in patients with advanced renal cell carcinoma (RCC).

The complete response (CR) rate was 5.5 percent and the partial response rate was 52.7 percent. The disease control rate was 78.2 percent.

“The combination of avelumab with axitnib shows encouraging antitumor activity as frontline treatment in patients with advanced renal cell carcinoma,” said lead investigator Toni Choueiri, M.D., clinical director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute.

The JAVELIN Renal 100 study included 55 patients with advanced clear-cell RCC. Patients had a median age of 60 years (range, 42-76), no prior systemic therapy for advanced RCC, and an ECOG performance status up to 1.

Over 95 percent of patients had favorable or intermediate risk per MSKCC criteria. Patients had one (45.5 percent), two (41.8 percent) or three (12.7 percent) metastatic sites.

In the dose-finding stage of the study, patients received a lead-in dose of Inlyta of 5 mg orally twice daily for seven days, followed by 10 mg/kg of Bavencio IV every two weeks plus Inlyta at 5 mg orally twice a day.

In the dose-expansion phase, patients could receive the same regimen as the dose-finding phase, or just start with 10 mg/kg of Bavencio IV every two weeks plus Inlyta at 5 mg orally twice a day.

Fifty-four of 55 patients received the combination, with 1 patient never receiving Inlyta. At the April 13, 2017, data cutoff, treatment was ongoing in 30 patients receiving Inlyta and 31 patients receiving Inlyta.

The median duration of Bavencio treatment was 36.5 weeks, and the median duration of Inlyta treatment was 34 weeks. Thirty-one patients had at least one dose reduction of Inlyta, and 10 patients had at least 1 dose escalation of Inlyta.

Thirty-two patients had confirmed responses, including three CRs, and 29 PRs. An additional patient still receiving therapy had an unconfirmed response. Eleven patients had stable disease, 10 had progressive disease, and two were not evaluable.

In 20 of 32 responders, the response occurred at the time of the first tumor assessment, and responses were ongoing in 24 of the responders.

Late responses occurred, as well. “Six patients had a late response — on or after week 18 —– and five of these patients remain on treatment,” said Choueiri.

Forty-five patients had tumor shrinkage, including 34 patients with shrinkage 30 percent or greater.

PD-L1 status was evaluable in 52 patients, and the researchers evaluated responses for PD-L1 cutoffs of greater than 1 percent and greater 5 percent.

At the 1 percent cutoff, the ORR was 65.9 percent (27/41) in PD-L1—positive patients and 36.4 percent (4/11) in PD-L1–negative patients. At the 5 percent cutoff, the ORR was 67.9 percent (19/28) in PD-L1–positive patients and 50.0 percent (12/25) in PD-L1–negative patients.

Progression-free and overall survival data are not yet mature.

All-grade adverse events (AEs) related to the treatment combination occurred in 53 patients. The most common all-grade AEs were diarrhea (52.7 percent), hypertension (45.5 percent), dysphonia (43.6 percent), and fatigue (43.6 percent).

Twenty-seven patients experienced grade three AEs, and five patients had grade four AEs. One patient died due to myocarditis. No patients who had a response died.

“Fewer grade 3 or higher AEs were considered related to avelumab than to axitinib,” Choueiri noted.

The majority of infusion-related reactions were grade 1 or 2 and occurred mainly during the first two infusions of Inlyta.

Seventeen patients experienced an immune-related AE, with only three being grade 3. Myocarditis was the only immune-related AE that led to death.

In his concluding remarks, Choueiri said, “These data support the ongoing phase 3 trial (NCT02684006) investigating the efficacy and safety of Inlyta plus Inlyta in untreated metastatic clear-cell advanced RCC.”