Calithera Biosciences, Inc. (NASDAQ:CALA), a clinical-stage, precision-oncology biopharmaceutical company, today announced that it has enrolled the first patient in a phase 2 clinical trial of sapanisertib (CB-228) in patients with relapsed/refractory NRF2 (NFE2L2)-mutated squamous non-small cell lung cancer (sqNSCLC).
NRF2 mutations are found in a considerable sub-population of patients across multiple solid tumor types. Sapanisertib is a potent and selective, dual mTORC 1/2 inhibitor that targets a key survival mechanism in tumors harboring these mutations. The compound previously demonstrated single-agent clinical activity in patients with relapsed/refractory NRF2-mutated sqNSCLC. Approximately 50,000 to 60,000 individuals are diagnosed with sqNSCLC in the United States alone each year, and about 15% of all sqNSCLC tumors harbor the NRF2 mutation.
“Our experience enrolling biomarker-driven clinical trials has allowed us to quickly advance sapanisertib since acquiring it from Takeda in the fourth quarter of last year. Enrollment of the first patient in this phase 2 study marks an important milestone for the program,” said Susan Molineaux, PhD, president and chief executive officer of Calithera. “Sapanisertib has the potential to be a first-in-class treatment for patients with NRF2-mutated squamous lung cancer, a patient population with poor prognosis and high unmet need. This study is designed to further validate the NRF2 mutation as a selection biomarker, and we plan to share data from the trial by the first quarter of 2023.”
The phase 2 trial (NCT05275673) is a multicenter, open-label study of sapanisertib monotherapy in patients with NRF2-mutated sqNSCLC whose disease has progressed on or after platinum-doublet chemotherapy and immune checkpoint inhibitor therapy (anti-PD-L1) with or without anti-CTLA-4, administered as separate lines of therapy or in combination. The study will evaluate sapanisertib 2 mg twice a day or 3 mg once a day in patients with sqNSCLC harboring either wild-type (WT) or mutated NRF2, as detected by next-generation sequencing.
The study is designed to confirm the selective activity of sapanisertib in NRF2-mutated tumors compared to WT tumors, and to refine dose in this biomarker-defined population. The primary endpoints of the study are investigator-assessed overall response rate (ORR) per RECIST v1.1, and safety. Secondary endpoints include duration of response, progression-free survival and overall survival.
Data from this study could position Calithera to initiate a study with registrational intent in biomarker-specific sqNSCLC populations.