Calithera Biosciences has enroled the first subject in a Phase II clinical trial of sapanisertib (CB-228) in relapsed/refractory NRF2 (NFE2L2)-mutated squamous non-small cell lung cancer (sqNSCLC) patients.

NRF2 mutations are seen in a substantial sub-population of patients across various kinds of solid tumours. 

A potent and selective, dual mTORC 1/2 inhibitor, sapanisertib acts on a crucial survival mechanism in tumours that harbour these mutations. 

The company acquired sapanisertib from Takeda in the fourth quarter of last year.

Earlier, this compound showed single-agent clinical activity in relapsed/refractory NRF2-mutated sqNSCLC patients. 

The multicentre, open-label trial will analyse sapanisertib monotherapy in NRF2-mutated sqNSCLC patients.

These subjects must have advanced on or following platinum-doublet chemotherapy and immune checkpoint inhibitor therapy (anti-PD-L1) irrespective of anti-CTLA-4.

In the trial, 2mg twice daily or 3mg once daily dose of sapanisertib will be administered in patients with sqNSCLC harbouring either wild-type (WT) or mutated NRF2.

The trial intends to validate sapanisertib’s selective activity in NRF2-mutated tumours versus WT tumours and refine the treatment dose in this biomarker-defined population.

Investigator-evaluated overall response rate (ORR) as per RECIST v1.1 and safety are the trial’s primary endpoints.

Duration of response, progression-free survival and overall survival are included as the secondary endpoints of the trial.

The trial findings would aid the company in commencing a registrational study in biomarker-specific sqNSCLC populations.

Calithera Biosciences president and CEO Susan Molineaux said: “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.”