Relay Therapeutics, Inc., a clinical-stage precision medicine company transforming the drug discovery process by leveraging unparalleled insights into protein motion, today announced the first patient has been dosed in a first-in-human clinical trial of RLY-4008 enriched for patients with intrahepatic cholangiocarcinoma (ICC) and other advanced solid tumors harboring a fibroblast growth factor receptor 2 (FGFR2) alteration. RLY-4008 is the only selective small molecule inhibitor of FGFR2 in clinical development.

“We are excited to bring RLY-4008, our second targeted therapeutic, into clinical development,” said Don Bergstrom, M.D., Ph.D., executive vice president of R&D of Relay Therapeutics. “FGFR2 altered tumors are known to respond clinically to pan-FGFR inhibitors but with limited benefit to patients. RLY-4008 is an exquisitely selective and purpose-built medicine, discovered with our Dynamo platform, designed to dramatically alter the course of disease for patients with FGFR2 altered cancers.”

The first-in-human trial is designed to evaluate the safety and tolerability of RLY-4008 in patients with advanced or metastatic solid tumors. The trial will predominantly enroll patients with molecularly identified FGFR2 fusions, mutations and amplifications during the dose escalation phase. Given RLY-4008’s strong preclinical activity against both primary oncogenic alterations and acquired pan-FGFR inhibitor resistance mutations, the trial is enrolling patients who are naïve to pan-FGFR inhibitors as well as those who have been exposed to prior therapy with pan-FGFR inhibitors.

In the expansion part of the trial, five cohorts are planned to evaluate genetically defined populations:

1) ICC patients with a FGFR2 fusion previously treated with a pan-FGFR inhibitor

2) ICC patients with a FGFR2 fusion not previously treated with a pan-FGFR inhibitor

3) patients with an FGFR2 fusion and solid tumor other than ICC

4) advanced, unresectable solid tumor patients with focal FGFR2 amplification

5) advanced, unresectable solid tumor patients with an oncogenic FGFR2 mutation. Trial objectives include evaluating safety, tolerability, pharmacokinetics and anti-tumor efficacy. The trial is designed to enroll up to 125 patients.

About RLY-4008
RLY-4008 is a potent, selective and oral small molecule inhibitor of FGFR2, a receptor tyrosine kinase that is frequently altered in certain cancers. FGFR2 is one of four members of the FGFR family, a set of closely related proteins with highly similar protein sequences and properties. Preclinically, RLY-4008 demonstrated FGFR2-dependent killing in cancer cell lines, while showing minimal inhibition of other targets, including other members of the FGFR family. RLY-4008 is currently being evaluated in a first-in-human trial designed to treat patients with advanced or metastatic FGFR2-altered solid tumors. To learn more about the first-in-human clinical trial of RLY-4008, please visit here.