Evexta Bio and Roche Ink Clinical Collaboration to Evaluate Rupitasertib Plus Giredestrant in ESR1-Mutated Metastatic Breast Cancer
核心洞察
Evexta Bio (搜索) and Roche have entered a clinical trial collaboration and supply agreement to evaluate rupitasertib in combination with giredestrant in ER+, HER2-, ESR1-mutated advanced/metastatic breast cancer.
Rupitasertib is a first-in-class oral dual-node PAM pathway inhibitor that selectively targets S6K (搜索) and AKT1/3 (搜索) while sparing AKT2 to potentially avoid hyperglycemia.
The Phase 1b study will enroll at least 15 patients and assess safety, tolerability, and preliminary anti-tumor activity, with initiation expected in Q4 2026.
Evexta Bio (搜索) S.A., a precision oncology company founded by Truffle Capital, announced today a clinical trial collaboration and supply agreement with Roche to evaluate rupitasertib, its first-in-class oral dual-node PAM pathway inhibitor, in combination with Roche's investigational selective estrogen receptor degrader (SERD) giredestrant. The planned Phase 1b study will target patients with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer and is expected to initiate in the fourth quarter of 2026.
The agreement represents the first clinical collaboration for Evexta Bio (搜索) with rupitasertib and the first such partnership for Roche involving giredestrant. Under the terms, Roche will supply giredestrant while Evexta Bio will sponsor and conduct the study.
Mechanism of Action and Rationale
Rupitasertib is a first-in-class oral dual-node inhibitor of the PI3K/AKT/mTOR (PAM) pathway (搜索), designed to selectively inhibit S6K (搜索) and AKT1/3 (搜索). The compound was purposefully and rationally engineered to target S6K for potent PAM pathway inhibition while simultaneously blocking AKT1/3 to disrupt the AKT compensatory feedback loop. Notably, rupitasertib spares AKT2, a design feature intended to avoid hyperglycemia—a known toxicity associated with broader PAM pathway inhibition. Evexta Bio (搜索) believes this selective profile may confer a superior efficacy and safety profile compared to other PAM pathway inhibitors.
Giredestrant, Roche's investigational agent, is a SERD that degrades the estrogen receptor, representing a complementary mechanism of action in hormone receptor-positive breast cancer.
Study Design and Objectives
The Phase 1b trial will assess the safety, tolerability, and preliminary anti-tumor activity of rupitasertib in combination with giredestrant. The study is designed to enroll at least 15 patients with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer in the second-line setting. Results from this study are expected to inform the future development strategy for the rupitasertib combination in this patient population.
Unmet Medical Need
Dr. Shawn M. Leland, PharmD, RPh, Board Chairman of Evexta Bio (搜索), emphasized the clinical significance of the collaboration: "We are very pleased and excited to partner with Roche on Evexta Bio's first clinical collaboration with rupitasertib. ER+, HER2-, ESR1-mutated breast cancer remains a significant unmet medical need. We are looking forward to being able to provide ER+, HER2-, ESR1-mutated breast cancer patients with the option to receive an all-oral regimen of a first-in-class, dual-node PAM pathway inhibitor and a SERD."
The all-oral combination regimen, if successful, could offer a convenient treatment option for patients with this molecularly defined subtype of breast cancer, where ESR1 mutations often emerge as a mechanism of resistance to endocrine therapy.
Evexta Bio (搜索)'s Pipeline
Beyond rupitasertib, Evexta Bio (搜索) is also advancing EVX020, a first-in-class KIF20A kinesin inhibitor that has demonstrated potent nonclinical efficacy in hematological and solid tumor models. The company, supported by Merck KGaA as a shareholder, maintains alliances with academic and industry partners including CNRS and the Paoli Calmettes Institute in Marseille, France.