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Calithera Biosciences Begins Phase II Study of Sapanisertib for Advanced NRF2-Mutant NSCLC

NEW YORK – Calithera Biosciences said on Wednesday that it has enrolled the first non-small cell lung cancer patient in a Phase II trial evaluating the NRF2-targeted mTORC1/2 inhibitor sapanisertib.

The Phase II trial is designed to evaluate the drug in roughly 50 relapsed or refractory, squamous NSCLC patients with wild-type and NRF2-mutated tumors. About 15 percent of all squamous NSCLC patients harbor such mutations, and according to Calithera, these patients have a poor prognosis and high unmet need.

To be eligible for the trial, patients must have progressed after platinum-doublet chemotherapy and a PD-L1 checkpoint inhibitor with or without anti-CTLA-4 immunotherapy. Patients will undergo next-generation sequencing at a lab with CLIA certification and accreditation from the College of American Pathologists to assess NFE2L2, the gene encoding the NRF2 protein.

Researchers will track patients' overall responses to the drug according to their biomarker status. Another aim of the study is to determine the best dose of sapanisertib for the biomarker-defined population. Secondary endpoints include duration of response, overall survival, and progression-free survival.

South San Francisco, California-based Calithera acquired sapanisertib from Takeda Oncology last year, and according to the firm, the agent previously showed single-agent activity in NRF2-mutated squamous NSCLC.

The firm plans to share data from the Phase II trial during the first quarter of 2023, and Calithera is optimistic that this could potentially set the stage for a registrational study of sapanisertib in the biomarker-defined NSCLC population.

As sapanisertib is advancing, Calithera has shuttered an internal program, in which it was evaluating the investigational drug telaglenastat with Merck's Keytruda (pembrolizumab) and chemotherapy as a front-line treatment for KEAP1/NRF2-mutated NSCLC. But due to lackluster efficacy in this and another renal cancer trial, however, the company in November decided to stop developing telaglenastat entirely.