Dr Thomas on the Efficacy of First-Line Ipatasertib Plus Pembrolizumab in HNSCC

“In this combination arm, we showed that the ORR was improved to 41% compared with 17% in the comparator arm of pembrolizumab alone.”

Jacob Stephen Thomas, MD, an assistant professor of clinical medicine and the service chief of LAC+USC Oncology at the Keck School of Medicine of the University of Southern California, discussed the rationale for and findings from a phase 2 trial (NCT05172258) investigating first-line ipatasertib in combination with pembrolizumab (Keytruda) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Currently, single-agent pembrolizumab is considered the standard of care for this patient population, a protocol established by data from the phase 3 KEYNOTE-048 study (NCT02358031), Thomas began. However, the historical response rate with pembrolizumab monotherapy is relatively low in this population, reaching only approximately 19%, he stated. The present phase 2 study was an effort to improve upon those historical benchmarks by introducing a more effective therapeutic approach for patients with HNSCC, he noted.

The research focused on the synergistic potential of ipatasertib, an AKT inhibitor, and the checkpoint inhibitor pembrolizumab. The comparator arm was pembrolizumab monotherapy. Ipatasertib was administered at 400 mg daily on days 1 through 14 of each 21-day cycle, whereas pembrolizumab was administered at 200 mg on day 1 of each cycle.

The results indicated that the combination therapy (n = 27) was highly effective, yielding an overall response rate (ORR) of 41%, including best responses of complete response (9.8%), partial response (20%), stable disease (27%), and progressive disease (25%). This figure stands in contrast to the 17% ORR recorded in the pembrolizumab-alone arm (n = 24). Although the combination was associated with increased toxicity, a finding consistent with the known adverse effect (AE) profile of AKT inhibitors, Thomas emphasized that these AEs remained both tolerable and manageable for patients throughout the course of treatment.

Disclosures: Thomas reported performing consulting or advisory roles with Conjupro Biotherapeutics and Kura Oncology.