Title
A Phase 2 Study of Ipatasertib in Combination with Pembrolizumab for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck

Description
This phase II trial compares the effect of adding ipatasertib to pembrolizumab (standard immunotherapy) vs. pembrolizumab alone in treating patients with squamous cell cancer of the head and neck that has come back (recurrent) or has spread to other places in the body (metastatic). Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of tumor cells and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ipatasertib in combination with pembrolizumab may be more effective than pembrolizumab alone in improving some outcomes in patients with recurrent/metastatic squamous cell cancer of the head and neck.

Objective
PRIMARY OBJECTIVE:

I. To compare progression-free survival (PFS) in first line relapsed/metastatic (R/M) head and neck squamous cell cancer (HNSCC) patients treated with the combination ipatasertib and pembrolizumab versus pembrolizumab monotherapy treatment.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of the combination ipatasertib and pembrolizumab in first line R/M HNSCC patients.
II. To describe overall response rate (ORR) and duration of response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in first line R/M HNSCC treated patients with the combination ipatasertib and pembrolizumab and pembrolizumab monotherapy treatment.
III. To assess changes in the tumor microenvironment by immunophenotyping with the combination ipatasertib and pembrolizumab and pembrolizumab monotherapy treatment.
IV. To assess changes in Akt, ERK, and MEK signaling with the combination ipatasertib and pembrolizumab and pembrolizumab monotherapy treatment.
V. To determine changes in immune-cell population in peripheral blood with the combination ipatasertib and pembrolizumab and pembrolizumab monotherapy treatment.

EXPLORATORY OBJECTIVE:

I. To investigate the relationship between the combination ipatasertib and pembrolizumab treatment and biomarkers which may predict response, such as tumor PD-L1 expression and alterations in the PI3K/AKT pathway.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and ipatasertib orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until disease progression, the next line of therapy is started, or death, whichever occurs first.

Treatment Experimental: Arm I (ipatasertib, pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1 and ipatasertib PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity.

Active Comparator: Arm II (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Head and Neck

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital