Repare cans plans for phase 3 cancer combo trial in latest money-saving move

Repare Therapeutics is continuing to strip back its pipeline in order to keep the cash flowing to its most promising programs.

Only five months after a round of pipeline prioritizations and layoffs, Repare’s leadership has been taking another look at the biotech’s portfolio and found more candidates it's willing to part ways with. Chief among them is a combination of the biotech’s PKMYT1 inhibitor lunresertib and ATR inhibitor camonsertib, dubbed Lunre+Camo.

As recently as last month, the biotech had been setting out plans for a phase 3 trial of the combo treatment for later in 2025 on the back of phase 1 data showing that Lunre+Camo achieved a 25.9% overall response rate in patients with endometrial cancer and 37.5% in individuals with platinum-resistant ovarian cancer.

These plans had been unaffected by Roche’s decision in February 2024 to walk away from a collaboration on camonsertib just days after the Big Pharma had dosed the first patient in a phase 2 trial.

But it sounds like Repare has now had second thoughts about going it alone, explaining in a postmarket release Jan. 9 that the company will now “seek partnering opportunities across its portfolio, including for Lunre+Camo prior to any start of pivotal development.”

“While Lunre+Camo demonstrated positive results from our phase 1 clinical trial, after careful consideration we have decided to progress this program into pivotal trials contingent on securing a strategic partner to fund further development,” Repare’s CEO Lloyd Segal said in the release.

While Repare is still assessing lunresertib in combination with Debiopharm’s WEE1 inhibitor as part of a collaboration, Repare said other plans to develop lunresertib or camonsertib separately or in combination—including an ongoing expansion study of camonsertib in non-small cell lung cancer—will be put on ice unless a partner can be found.

With $153 million to hand in cash and equivalents, Repare said the savings made from halting work on these assets, “combined with planned cost and headcount reductions,” are expected to extend Repare’s financial runway into mid-2027.

In response to Fierce Biotech's question to Repare as to whether the layoffs it referenced yesterday are limited to the 25% head count reduction set out in August 2024, a spokesperson said it "will be additional headcount reductions, separate from those announced last summer."  While not divulging any numbers, Repare told Fierce Biotech that it "intend(s) to implement our headcount reductions later this quarter."

Repare had 179 full-time employees as of February 2024, of which 143 were primarily engaged in some form of R&D and 36 were focused on management or general and administrative activities.

The layoffs back in August were tied to Repare’s decision to scale back its preclinical work. At the time, the justification was to focus on the company’s “most promising and advanced precision oncology programs,” which included lunresertib or camonsertib.

The aim of the latest pipeline changes is to channel the company’s resources to its phase 1 clinical assets, namely the PLK4 inhibitor RP-1664 and the Polθ ATPase inhibitor RP-3467. RP-1664 is currently being evaluated as a monotherapy in adolescent patients with TRIM37-high solid tumors, with the study due to expand to patients with pediatric neuroblastoma later this year.

Meanwhile, Repare is dosing patients in a phase 1 study of RP-3467 alone and in combination with Lynparza in patients with ovarian cancer, breast cancer, castration-resistant prostate cancer and pancreatic adenocarcinoma, with a readout penciled in for the third quarter.

“We are focused on achieving near-term inflection points for our phase 1 clinical assets, RP-1664 and RP-3467, both of which have the potential to address significant unmet patient needs and deliver important catalysts in 2025,” Segal said in the release. “Combined with other initiatives, these changes, which we will implement later this quarter, provide the foundation for meaningful value creation.”