Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS

Description

Background:

* Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide, with approximately 60,000 patients diagnosed annually in the United States.
* Only 14% of HNSCC patients have structural defects in the genes encoding for the human leukocyte antigens (HLA) class I components, while a higher percentage of these tumors show downregulation of HLA class I components by immunohistochemistry supports those epigenetic mechanisms may be involved in the deregulation of these genes.
* Valemetostat (DS-3201) is an enhancer of zeste homolog 1 and 2 (EZH1/2) dual inhibitor that is actively being investigated in phase I and II trials for hematologic malignancies and is approved for adult T-cell leukemia/lymphoma (ATL) indication in Japan.
* Patients with recurrent or metastatic (R/M) pembrolizumab-na(SqrRoot) ve human papillomavirus (HPV)-negative HNSCC have a low 6-month progression-free survival (PFS) (28%) with pembrolizumab monotherapy, thus novel interventions are needed to increase the efficacy of pembrolizumab.

Objectives:

Phase Ib:

* To determine the recommended phase II dose (RP2D) of valemetostat in combination with pembrolizumab.
* To evaluate the safety of valemetostat in combination with pembrolizumab.

Phase II:

-To determine the disease control rate (DCR)=partial response (PR) + complete response (CR) + stable disease (SD).

Eligibility:

-Participants must have a diagnosis of locoregionally recurrent or metastatic (R/M) HPVnegative (Phase Ib and Phase II) or positive HNSCC (Phase Ib only): oral cavity, tonsil, pharynx, hypopharynx, larynx. Note: Nasopharyngeal carcinoma and cutaneous squamous cell carcinoma (SCC) are excluded

OR

(R/M) squamous non-small cell lung cancer (NSCLC) (Phase Ib only)

OR

(R/M) sinonasal carcinomas of the head and neck (Phase Ib only).

* Age >18 years.
* Adequate organ and marrow function.

Design:

* This is an open-label multicenter phase Ib/II study to evaluate the safety and efficacy of the combined treatment of valemetostat and pembrolizumab.
* During phase Ib we will estimate the RP2D of the valemetostat in combination with pembrolizumab.
* During phase II we will examine the efficacy and continue to evaluate the safety of the study regimen at the RP2D of the valemetostat in combination with pembrolizumab.
* Participants will receive treatment in cycles consisting of 21 (+/- 3) days for 2 years.