Title
Phase II Trial of Androgen Deprivation Therapy (ADT) and Pembrolizumab for Advanced Stage Androgen Receptor-Positive Salivary Gland Carcinoma: Big Ten Cancer Research Consortium BTCRC-HN17-111

Description
This is a Phase II multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation. Eligible patients will include both those with no prior systemic therapy and those who have failed prior systemic therapy. Patients who have received previous ADT or immunotherapy will be excluded.

ADT will consist of goserelin acetate every 4 weeks with the first injection given approximately 2 weeks prior to the first dose of pembrolizumab. Pembrolizumab 200 mg will be given on day 1 of 21-day cycles, starting 2 weeks after initiation of goserelin acetate. Each 21-day period is considered a treatment cycle with therapy continuing for up to 35 cycles, until disease progression, significant toxicity, or patient refusal. Except for fatigue, we do not expect overlapping toxicities with pembrolizumab and ADT, thus the starting doses will be the FDA-approved doses.

This study will use a Simon 2-stage phase II trial design. The first stage of the Simon 2-stage design will have a sample size of nine patients. If at least two patients have an objective response by RECIST 1.1 then enrollment will proceed to stage 2 with an additional 11 patients, to a goal of 20 patients. If less than 4 patients out of 20 respond, then the combination treatment will be rejected.

Patients will be staged with CT of neck, chest, abdomen, and pelvis at baseline and every 12 weeks while on study. Treatment with both ADT and pembrolizumab will continue until disease progression or intolerable side effects.

Archival tumor biopsy tissue must be available at baseline to evaluate for expression of androgen receptor (AR), PD-L1, and tumor-infiltrating lymphocytes (TIL). An optional biopsy will be performed after 4 doses of pembrolizumab to evaluate immune response to combined therapy.

Blood will be collected at baseline, cycle 1 day 1, cycle 2 day 1 and cycle 3 day 1 to evaluate for change in lymphocyte subsets by flow cytometry.

Objective
Primary Objective: To determine the objective response rate (ORR) of pembrolizumab when given with goserelin in patients with locally recurrent or metastatic androgen receptor-positive salivary gland carcinoma not amenable to curative-intent treatment with surgery or radiation per RECIST 1.1.

Secondary Objectives:
1) Determine progression free survival (PFS) at 12 months
2) Disease control rate as defined by stable disease plus objective response
(SD+PR+CR).
3) Determine overall survival (OS) at 12 months
4) To evaluate the safety and tolerability of pembrolizumab when given
with goserelin

Exploratory Objectives:
1) Determine the ORR as per iRECIST
2) Assess response rate by PD-L1 expression using combined positive scoring (CPS) (<1%, 1-50%, >50%).
3) Characterize intra-tumoral immune response as measured by tumor infiltrating lymphocytes, PD-1 expression on T cells, and PD-L1 expression on tumor cells, comparing biopsy specimens at study entry prior to therapy, post-ADT/pembrolizumab.
4) Characterize systemic immune response by peripheral blood flow cytometry measuring proliferative response in immune subsets, PD-1 positivity in PBMCs, CD28 expression on T cells, and peripheral cytokine analysis, comparing data pre- and post-therapy.

Treatment Experimental: Goserelin Acetate + Pembrolizumab
Goserelin Acetate, 3.6 mg, every four weeks, SQ Pembrolizumab, 200mg, every three weeks, IV
Drug: Goserelin Acetate
Goserelin Acetate, SQ, Q4W
Drug: Pembrolizumab
Pembrolizumab, IV, Q3W

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