Sensei Biotherapeutics Doses First Patient in Phase 1b/2 Trial of PIKTOR in HR+/HER2- Advanced Breast Cancer

Sensei Biotherapeutics has dosed the first patient in a Phase 1b/2 trial evaluating PIKTOR, an investigational all-oral combination of the mTOR1/2 inhibitor sapanisertib and the PI3K-alpha inhibitor serabelisib, in patients with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.

The study, designated FTH-PIK-101, is a multi-center, dose-escalation Phase 1b/2 trial evaluating PIKTOR in combination with fulvestrant and/or other anticancer therapies. The trial is enrolling approximately 32 patients with HR-positive, HER2-negative advanced or metastatic breast cancer, regardless of mutational status. The study is measuring safety, preliminary efficacy, initial objective response rate, progression-free survival, overall survival, and clinical benefit rate as secondary outcomes.

PIKTOR became Sensei's lead program following its acquisition of Faeth Therapeutics earlier this year. The combination is designed to inhibit multiple nodes of the PI3K/AKT/mTOR growth pathway simultaneously through PI3K-alpha and dual mTORC1/2 targeting, which the company hopes will better block tumors' ability to evade treatment. The PI3K/AKT/mTOR signaling pathway is altered in approximately half of HR+/HER2- breast cancer cases.

In a previous investigator-initiated Phase 1b trial of PIKTOR plus paclitaxel in patients with advanced breast, endometrial, or ovarian cancer who had failed an average of four previous lines of treatment, the regimen demonstrated a 47% overall response rate among 15 evaluable patients. Among patients whose tumors harbored PI3K pathway mutations, the response rate was 71%. Three patients had complete responses, all in endometrial cancer.

"In our earlier trial, patients who had exhausted multiple lines of therapy, including chemotherapy, responded to the PIKTOR plus paclitaxel combination, and several had complete responses," the company's chief operating officer stated. "PIK-101 now takes that same oral combination into breast cancer, where a large share of tumors carry the pathway alterations that PIKTOR is designed to target."

Sensei is also conducting Study FTH-PIK-201, an ongoing multicenter, open-label, single-arm Phase 2 study in approximately 40 patients with advanced endometrial cancer, with results expected this year. That trial is evaluating PIKTOR plus paclitaxel in patients whose disease progressed after platinum-based chemotherapy and/or checkpoint inhibitors, and includes a substudy evaluating PIKTOR plus paclitaxel combined with an insulin-suppressing diet.

Sapanisertib plus paclitaxel has also shown promise in ovarian cancer, producing a mean progression-free survival of 5.8 months versus 4.0 months with paclitaxel alone in the Phase 2 investigator-sponsored Dice trial in platinum-resistant patients.

The all-stock acquisition of Faeth Therapeutics coincided with a $200 million private placement. The company stated the proceeds would also be used to complete an ongoing Phase 1/2 solid tumor trial of solnerstotug, its VISTA inhibitor.