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Relay Therapeutics Initiates Human Study of Selective FGFR2 Inhibitor RLY-4008

NEW YORK – Clinical stage drug company Relay Therapeutics said on Thursday that it has dosed the first patient in the first-in-human study of RLY-4008 in FGFR2-altered intrahepatic cholangiocarcinoma and other advanced solid tumors.

According to the Cambridge, Massachusetts-based biotechnology firm, RLY-4008 is unique as a selective small molecule FGFR2 inhibitor. "FGFR2 altered tumors are known to respond clinically to pan-FGFR inhibitors but with limited benefit to patients," Don Bergstrom, Relay's executive VP of R&D, said in a statement. Relay discovered RLY-4008 using its Dynamo platform and designed it to selectively interrogate FGFR2 altered cancers.

The US Food and Drug Administration in April 2019 granted accelerated approval to Janssen Pharmaceutical's pan-FGFR inhibitor erdafitinib (Balversa) for metastatic bladder cancer patients who have progressed on platinum-based chemotherapy and who harbor alterations in FGFR3 or FGFR2 genes. A year later, the agency approved pemigatinib (Incyte's Pemazyre), an inhibitor of FGFR isoforms 1, 2 and 3, for previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.

In preclinical studies, RLY-4008 has shown activity against primary tumor alterations and acquired mutations that confer resistance to pan-FGFR inhibitors. As such, the recently launched first-in-human trial will gauge the safety, tolerability, and initial efficacy of RLY-4008 in patients who are naïve to or who have previously received pan-FGFR inhibitors.

The study will include a dose escalation and expansion phase and enroll up to 125 patients across five cohorts. The first two cohorts will enroll intrahepatic cholangiocarcinoma patients with FGFR2 fusions who have and have not received a prior pan-FGFR inhibitor; the third cohort will include patients with FGFR2 fusion-positive solid tumors; the fourth cohort will enroll those with advanced or unresectable solid tumors with focal FGFR2 amplifications; and the fifth cohort will involve patients with FGFR2-mutated advanced, unresectable solid cancers.