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Roche partners with Evexta Bio to test dual-node inhibitor against resistant breast cancer

Roche partners with Evexta Bio to test dual-node inhibitor against resistant breast cancer

France-based Evexta Bio S.A. and Roche announced a clinical trial collaboration and supply agreement to evaluate rupitasertib in combination with giredestrant in patients with estrogen receptor-positive (ER+), HER2-negative, ESR1-mutated advanced or metastatic breast cancer. Under the agreement, Evexta Bio will sponsor and conduct the Phase Ib study, while Roche will supply giredestrant. Financial terms were not disclosed.

Rupitasertib is an oral small molecule that selectively inhibits S6K and the AKT1 and AKT3 isoforms, targeting two nodes within the PI3K/AKT/mTOR pathway while sparing AKT2. Evexta Bio said the approach is intended to suppress compensatory pathway signaling while potentially reducing the hyperglycemia associated with broader AKT inhibition. Giredestrant is Roche's investigational oral selective estrogen receptor degrader (SERD) and full estrogen receptor antagonist, designed to degrade the estrogen receptor and block estrogen-driven tumor growth, including in ESR1-mutated disease where ligand-independent receptor activation can drive endocrine resistance.

The Phase Ib study will evaluate the safety, tolerability and preliminary anti-tumor activity of the combination in at least 15 patients, with study initiation targeted for Q4 2026.

The collaboration marks Evexta Bio's first clinical agreement involving rupitasertib. The company was founded by Truffle Capital, which also founded France-based Abivax (Nasdaq: ABVX) and Carvolix, and counts Merck KGaA as a shareholder.

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Rupitasertib enters an increasingly competitive treatment landscape for ER+, HER2-negative advanced breast cancer. Approved therapies targeting the PI3K/AKT/mTOR pathway include Novartis' Piqray (alpelisib), Roche's Itovebi (inavolisib), AstraZeneca's Truqap (capivasertib) and Celcuity's Revtorpyk (gedatolisib), although they are approved for different biomarker-defined patient populations and combination regimens. Meanwhile, oral estrogen receptor-targeting therapies such as Menarini Group's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant) have further raised the efficacy benchmark for endocrine therapy, setting a high bar that rupitasertib's dual-node mechanism will ultimately need to clear.


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