Sapanisertib Receives Fast Track Designation by the FDA for Advanced NSCLC


Fast track designation was granted to sapanisertib by the FDA for patients with unresectable or metastatic squamous cell non–small cell lung cancer who have an NRF2 mutation.

The FDA has granted fast track designation to sapanisertib (CB-228), an mTORC 1/2 inhibitor, for patients with unresectable or metastatic squamous cell non–small cell lung cancer (NSCLC) who have a NRF2 mutation and received prior platinum-based chemotherapy and immune checkpoint inhibitor therapy, according to a press release from Calithera Biosciences.

The fast track designation is based on data from a phase 2 trial (NCT05275673) that was designed to determine the activity of sapanisertib in patients who have NRF2-mutated tumors vs wild-type tumors. Treatment with sapanisertib yielded a confirmed overall response rate (ORR) of 27%, and a median progression-free survival (PFS) of 8.9 months (95% CI, 7.0-not reached). Additional data from this study will be shared in the first quarter of 2023.

“While there have been significant advances in targeted treatments for lung cancer, little progress has been made specifically for patients with squamous lung cancer. In addition, we know that patients with lung cancers that harbor mutations in the NRF2/KEAP1 pathway typically have poorer outcomes than those whose tumors do not have these mutations,” Susan Molineaux, chief executive officer at Calithera, said in the press release.

The multicenter, open-label study had an estimated enrollment of 50 patients who had disease progression on or after platinum-doublet chemotherapy and immune checkpoint inhibitor therapy with or without anti–CTLA-4. Patients received sapanisertib either at 2 mg twice a day or 3 mg once a day.

The primary end points were investigator-assessed ORR and adverse effects (AEs) including number of patients with AEs, serious AEs, death, and discontinuation due to AEs. The secondary end points were duration of response, PFS, and overall survival at 6 months, 12 months, and 36 months.

Patients were included in the trial if they had stage IV squamous NSCLC, disease progression during or after systemic therapy, or had a study-eligible mutation determined by next-generation sequencing. Additional eligibility criteria included having a radiographically measurable lesion of 10 mm or more, target lesions from a previously irradiated area, an ECOG performance status of 0 or 1, and adequate organ function.

Patients were excluded from the study if they had non-squamous cell histology or mixed histology tumors, a prior concurrent malignancy which may interfere with the safety or efficacy assessment of the study, or an investigational agent within 4 weeks, chemotherapy within 3 weeks, or any radiotherapy within 2 weeks. Additionally, patients were not able to have any major surgery or anti-cancer therapy within 4 weeks of treatment, be unable or unwilling to discontinue a proton pump inhibitor, have interstitial lung disease, or have an infection that requires more than 5 days of antibiotics. Patients must also not have any condition that could hinder the treatment protocol, receive 10 mg or greater or prednisone, or have significant cardiovascular disease.


Calithera receives FDA fast track designation for sapanisertib for the treatment of NRF2-mutated squamous lung cancer. News Release. Calithera Biosciences. October 3, 2022. Accessed October 4, 2022.

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