NEW YORK – Repare Therapeutics and Debiopharm on Tuesday said they dosed the first patient with the PKMYT1 inhibitor lunresertib and the WEE1 kinase inhibitor Debio 0123 in a new arm of Repare's ongoing Phase I/Ib MYTHIC trial.
In the trial, which Repare launched in May 2021, researchers are evaluating the safety and tolerability of Repare's lunresertib (RP-6306) alone and in combination with Debio 0123 or the ATR inhibitor camonsertib (RP-3500) in patients with locally advanced or metastatic tumors that are resistant or refractory to therapy and that test positive for targetable tumor biomarkers by next-generation sequencing. To participate in the trial, patients must have tumors bearing CCNE1 amplifications, FBXW7 deleterious mutations, or PPP2R1A deleterious mutations.
As primary endpoints of the trial, investigators are assessing safety and tolerability; the maximum tolerated dose of lunresertib alone and in combination with the other two investigational drugs; and other measures related to dosing and bioavailability. Researchers will also look for preliminary signs of anti-tumor activity via changes in tumor size from baseline, the objective response rate, overall response rate, tumor marker response, duration of response, clinical benefit rate, and progression-free survival.
Lausanne, Switzerland-based Debiopharm and Montreal-based Repare teamed up in January to study Debio 0123 with lunresertib based on preclinical in vivo data and other data indicating rapid tumor regressions and high clinical tolerability. "This combination provides us a unique opportunity to optimize dosing between two selective compounds and overcome limitations inherent to dual-inhibitor approaches," Maria Koehler, executive VP and chief medical officer at Repare, said in a statement. "We expect this clinical collaboration will allow us to optimize the excellent synergy we saw preclinically to maximize patient benefit and tolerability."
Debiopharm is also studying Debio 0123 in a Phase I trial as a monotherapy in biomarker-selected solid tumors, and it has two other precision oncology candidates in its pipeline: the CA IX-targeted radiotherapy Debio 0228 and the IAP antagonist xevinapant for head and neck cancer.
Meanwhile, Repare is evaluating its PLK4 inhibitor RP-1664 in the Phase I LIONS trial as a treatment for patients with advanced tumors bearing TRIM37 gains, amplifications, and other genetic alterations. Repare also recently regained rights to camonsertib after Roche terminated a 2022 collaboration agreement.