Calithera Biosciences, Inc. announced that the U.S. Food & Drug Administration (FDA) has granted Fast Track designation for the company's investigational mTORC 1/2 inhibitor sapanisertib (CB-228) for the treatment of adult patients with unresectable or metastatic squamous non-small cell lung cancer (sqNSCLC) whose tumors have a mutation in nuclear factor erythroid 2-related factor (NFE2L2, also called NRF2) and who have received prior platinum-based chemotherapy and immune checkpoint inhibitor therapy. RF2 mutations are found across multiple solid tumor types, with these mutations occurring in approximately 15% of sqNSCLC patients. Sapanisertib targets a key survival mechanism in NRF2-mutated tumor cells.

In a recent investigator-initiated Phase 2 trial, the compound was well-tolerated and demonstrated durable single-agent activity with a 27% (or 3/11) confirmed overall response rate (ORR) and median progression free survival (PFS) of 8.9 months (95% CI: 7 months, not reached) in heavily pretreated patients with NRF2-mutated sqNSCLC. Calithera's ongoing Phase 2 trial (NCT05275673) is a multi-center, 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. The study is evaluating 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. Calithera plans to share data from this study by the first quarter of 2023.

Data generated from this open-label study could position the company to initiate a study with registrational intent in biomarker specific sqNSCLC populations. The FDA grants Fast Track designation to facilitate development and expedite the review of therapies with the potential to treat a serious condition where there is an unmet medical need. A therapeutic that receives Fast Track designation can benefit from early and frequent communication with the agency, in addition to a rolling submission of the marketing application, with potential pathways for expedited approval that have the objective of getting important new therapies to patients more quickly.