Relay Therapeutics, Inc. provided an update for two of its ongoing first-in-human trials, RLY-2608, the first known allosteric, pan-mutant and isoform-selective PI3Ka inhibitor in clinical development, and RLY-4008, a highly selective, irreversible and oral small molecule inhibitor of FGFR2. RLY-2608 First-in-Human Trial: For RLY-2608, Relay Therapeutics dosed the first patient in a first-in-human trial for patients with advanced solid tumors with a PIK3CA (PI3Ka) mutation. The first-in-human trial for RLY-2608 is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity, and will consist of two separate arms. The first arm will assess RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors with PI3Ka mutation, while the second arm will evaluate RLY-2608 in combination with fulvestrant for patients with PI3Ka-mutant, HR+, HER2– locally advanced or metastatic breast cancer.

Each arm will have two parts, first a dose escalation part to determine the maximum tolerated dose and/or recommended phase 2 dose, followed by a dose expansion part to evaluate RLY-2608 in genomically defined populations. In the dose expansion part of the trial for RLY-2608 as a single agent, patients with the following unresectable or metastatic solid tumors with a PI3Ka mutation per local assessment will be enrolled in the following groups: 1) clear cell ovarian cancer; 2) head and neck squamous cell carcinoma; 3) cervical cancer; 4) other solid tumors; and 5) unresectable or metastatic solid tumors with PIK3CA double mutations defined as major (E542X, E545X, or H1047X), plus =1 additional PI3Ka mutations. For RLY-2608 in combination with fulvestrant, men or postmenopausal women with HR+, HER2– advanced or metastatic breast cancer patients with PI3Ka mutations will be enrolled in the following groups: 1) patients who have not received prior treatment with a PI3Ka inhibitor; and 2) patients who are intolerant to PI3Ka inhibitors.

The trial is designed to enroll approximately 190 patients between both arms. RLY-4008 Expansion Cohorts: Relay Therapeutics initiated expansion cohorts last month for the first-in-human trial for RLY-4008 in patients with FGFR2-altered cholangiocarcinoma, breast cancer and other solid tumors. The ongoing first-in-human trial for RLY-4008 is designed to evaluate the safety, tolerability, pharmacokinetics and anti-tumor efficacy. Following a thorough assessment of the dose escalation data, the expansion portion of the trial has been initiated at a dose of 70 mg once daily.

The expansion part of the trial has five cohorts planned to evaluate genetically defined populations: 1) intrahepatic cholangiocarcinoma (ICC) patients with an FGFR2 fusion previously treated with a pan-FGFR inhibitor; 2) ICC patients with an 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. Relay Therapeutics will continue to monitor the dose escalation data and expansion cohorts to determine if other doses or schedules should be evaluated.