Evexta Bio partners with Roche for a Phase 1b trial combining rupitasertib and giredestrant in ER+/HER2-, ESR1-mutated advanced breast cancer. Q4 2026 launch.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Evexta Bio has entered a clinical collaboration and supply agreement with Roche to evaluate the investigational combination of rupitasertib and giredestrant in patients with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The planned Phase 1b study will assess the safety, tolerability, and preliminary anti-tumor activity of the all-oral combination in the second-line treatment setting. Enrollment is expected to begin in the fourth quarter of 2026.
The collaboration marks Evexta Bio’s first clinical partnership involving rupitasertib and Roche’s first collaboration with the investigational selective estrogen receptor degrader (SERD) giredestrant in this setting. Findings from the study are expected to help define future clinical development strategies for rupitasertib-based combination therapy in hormone receptor-positive breast cancer.
Dual-Node Approach Targets a Key Resistance Pathway
Rupitasertib is a first-in-class oral dual-node inhibitor of the PI3K/AKT/mTOR (PAM) signaling pathway. Unlike conventional PAM pathway inhibitors, it selectively inhibits S6 kinase (S6K) and AKT1/3 while sparing AKT2.
This selective profile is intended to maintain potent inhibition of the PAM pathway, suppress compensatory AKT signaling, and reduce the risk of treatment-related hyperglycemia, a common limitation of several existing AKT inhibitors. By combining rupitasertib with giredestrant, an investigational oral SERD that degrades the estrogen receptor, researchers aim to address multiple mechanisms of endocrine resistance in ESR1-mutated breast cancer.
ESR1 mutations are a recognized mechanism of resistance to endocrine therapy in ER-positive metastatic breast cancer and remain an important therapeutic challenge after progression on first-line treatment.
Phase 1b Trial to Enroll at Least 15 Patients
Under the agreement, Roche will supply giredestrant, while Evexta Bio will sponsor and conduct the Phase 1b trial.
The study will enroll at least 15 patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. Investigators will primarily evaluate the safety and tolerability of the combination while also assessing preliminary anti-tumor activity to determine whether dual inhibition of estrogen receptor signaling and the PAM pathway warrants further clinical development.
The trial is expected to initiate during the fourth quarter of 2026.
Leadership Highlights the Potential of an All-Oral Combination
Dr. Shawn M. Leland, PharmD, RPh, Chairman of the Board at Evexta Bio, said the collaboration represents an important milestone for the company and its lead oncology program. He noted that patients with ER-positive, HER2-negative, ESR1-mutated breast cancer continue to face significant unmet medical needs despite recent advances in endocrine therapy.
According to Leland, the collaboration with Roche provides an opportunity to evaluate an all-oral treatment regimen combining a first-in-class dual-node PAM pathway inhibitor with an investigational SERD in a patient population with limited therapeutic options.
Future Development
If the Phase 1b study demonstrates an acceptable safety profile and encouraging early anti-tumor activity, the results could support broader clinical development of rupitasertib in combination with endocrine therapies for hormone receptor-positive breast cancer. The collaboration also establishes Evexta Bio’s first strategic clinical partnership and may guide future combination strategies for rupitasertib across endocrine-resistant breast cancer populations.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.