Primary results from a global phase II trial of futibatinib, an irreversible FGFR1-4 inhibitor, showed positive results against intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements. The highly selective and irreversible inhibitor had an objective response rate of 41.7 percent in previously treated patients. About 14 percent of iCCA tumors have FGFR2 fusions.

“Responses to futibatinib were both rapid and durable,” said Lipika Goyal, MD, Massachusetts General Hospital Cancer Center. “The median time to response was 2.5 months, and the median duration of response was 9.7 months. Treatment is ongoing for nearly a third of patients in the trial.”

Goyal revealed the results of the FOENIX-CCA2 trial during Targeted Therapy and Ovarian Cancer Trials on Sunday, April 11. Registrants can watch a replay of this Clinical Trials Plenary anytime until June 21, 2021.

All patients in the trial reported adverse events, and two discontinued treatment. The trial included 105 patients with unresectable or metastatic iCCA across 36 international sites. Patients were heavily pretreated, with over half having received two or more prior therapies. All patients have been followed for at least six months, and median follow up was 17.1 months.

Promising results against RET fusions in non-lung, non-thyroid solid tumors

Selpercatinib, a highly selective RET inhibitor approved for use in RET fusion-positive non-small cell lung cancer (NSCLC) and thyroid cancers, also shows strong activity against other RET-positive solid tumors. LIBRETTO-001, a global phase I/II dose escalation and dose expansion trial, showed an objective response rate of 47 percent in a subset of patients with pancreatic, colon, breast, and other non-NSCLC/non-thyroid tumors.

NSCLC patients made up 80.7 percent of the trial, thyroid 10.7 percent, and other solid tumors 8.6 percent. Patients had received a median of two prior therapies.

“The median duration of response had not been reached at a median follow-up of 13 months,” said Vivek Subbiah, MD, The University of Texas MD Anderson Cancer Center. “Nearly three-quarters of responses were ongoing.”

Safety profiles were similar across NSCLC, thyroid, and other tumor types, Subbiah said. The most frequent adverse events in the non-NSCLC/non-thyroid cohort were increased liver enzymes, dry mouth, hypertension, diarrhea, fatigue, nausea, and abdominal pain. No patients in the cohort discontinued treatment because of adverse events.

“These results tell us that broad-based genomic profiling is essential to identify actionable oncogenic drivers, including RET fusions,” Subbiah said.

Positive early results for immune checkpoint/TKI combo in advanced platinum-resistant ovarian cancer

A trial of tislelizumab, an anti-PD-1 antibody, and sitravatinib, a tyrosine kinase inhibitor, showed acceptable safety profile and potential antitumor activity in a phase Ib trial involving 60 patients across six centers in Australia. The patients had advanced platinum-resistant ovarian cancer (PROC) and were followed for a median of six months.

Nearly all patients, 97 percent, reported at least one adverse event (AE), said Jeffrey Goh, MBBS, ICON Cancer Centre, and 40 percent had a treatment-related AE. The mean duration of treatment was 81 weeks for tislelizumab and 15 weeks for sitravatinib. There were four deaths, none treatment related.

The objective response rate was 26 percent, disease control rate was 77 percent, and median duration of response was 4.7 months. Overall survival and progression-free survival have not yet been reached.

“The results from this study support tislelizumab in combination with sitravatinib as a potential treatment option for patients with PROC,” Goh said. “Further investigation in a larger trial is warranted.”

Final phase I results for intraperitoneal cantrixil in treatment-refractory ovarian cancer

Final results from a first-in-human study of cantrixil by intraperitoneal infusion for treatment-refractory ovarian cancer are in. Cantrixil, a third-generation benzopyran, showed acceptable safety with a maximum tolerable dose of 5 mg/kg in a phase I open label study with 25 patients across six centers in Australia and the U.S.

Patients in the trial averaged 62 years of age, had stage III/IV ovarian cancer at entry, and a median of five prior lines of therapy.

The objective response rate was 19 percent, disease control rate was 56 percent, and median progression-free survival was 13.1 weeks, said Jermaine Coward, MBBS, PhD, University of Queensland School of Medicine and ICON Cancer Centre. A post hoc subgroup analysis revealed a longer PFS among patients with platinum-refractory disease, 23.8 weeks.

An exploratory analysis showed a reduction in multiple stem-cell markers at the end of treatment. Preclinical and clinical data suggest that drug-resistant ovarian cancer stem cells may drive disease recurrence in treatment-refractory disease.

“These findings from the first-in-human study demonstrate the potential for prolonged survival in advanced ovarian cancer,” Coward said. “They warrant further investigation of cantrixil, particularly in earlier lines of therapy.”