The FDA has only approved a handful of therapies to treat tumors based on a biomarker and regardless of their location. With new clinical data, Johnson & Johnson hopes Balversa could be the next drug up for a pan-tumor nod.
Balversa shrank tumors in 26.4% of patients with various cancers bearing FGFR alterations. J&J’s Janssen will present the data, collected at a planned interim analysis of a phase 2 trial called RAGNAR, at the 2022 American Society of Clinical Oncology annual meeting.
Janssen will talk to regulators including the FDA to “explore what the opportunities are” for potential pan-tumor applications of Balversa based on the current results, Mark Wildgust, Ph.D., Janssen’s vice president of oncology global medical affairs, said in an interview with Fierce Pharma.
FGFR alterations are rare and are believed to be a driving force behind tumor formation, Wildgust explained. Balversa got its initial FDA go-ahead in 2019 for previously treated bladder cancer with FGFR3 or FGFR2 mutations. But there aren't any therapies available broadly for patients with FGFR-altered cancers.
The RAGNAR trial recorded responses across 14 tumor types including bile duct, brain, breast, endometrial, esophageal, lung, ovarian, pancreatic and others. The study didn't include bladder cancer patients.
The clinical trial tested Balversa in a a group of 178 patients who had exhausted other therapies. Disease control rate, which includes those with stable disease, reached 75.3%. Only 9% of the patients responded to their previous line of therapy before entering the RAGNAR trial.
The response rates were similar between FGFR mutations and fusions, at 26.8% and 27%, respectively. Median duration of response was 7.1 months, and the patients lived a median 10.9 months.
The data “definitely suggest that [Balversa] has a broad role to play in patients with FGFR-altered malignancies,” Wildgust said. The RAGNAR trial remains ongoing and aims to enroll altogether 336 participants, according to ClinicalTrials.gov.
Janssen’s strategy to potentially use the existing data to seek an FDA approval looks plausible. Under the accelerated approval pathway, the FDA has in the past offered biomarker-driven pan-tumor indications to cancer drugs based on early tumor shrinkage data. As Wildgust noted, RAGNAR is so far the largest tumor-agnostic clinical trial of a targeted therapy to date.
Back in 2017, the FDA doled out its very first tumor-agnostic indication to Merck & Co.’s PD-1 inhibitor Keytruda for the treatment of microsatellite instability-high or mismatch repair deficient solid tumors. That was based on data from 149 patients across five single-arm clinical trials.
Then in 2018, Bayer’s Vitrakvi won an accelerated approval for solid tumors that have an NTRK gene fusion. At that time, the small-molecule drug showed a 75% overall response rate among 55 patients across three clinical trials.
With a small label in bladder cancer, Balversa didn’t earn a place in J&J’s 2021 annual report. But the company has touted the drug has blockbuster potential. Other FGFR inhibitors in development include Incyte’s Pemazyre and BridgeBio’s Truseltiq, both approved to treat bile duct cancer with FGFR2 fusion or rearrangements.