Title
Pilot Study of INCB081776 Together with Palliative Radiation and Anti-PD-1 Checkpoint Blockade with Pembrolizumab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Description
This study is evaluating INCB081776 when given in combination with the checkpoint inhibitor pembrolizumab and palliative radiation therapy in patients with metastatic or recurrent metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). 12 participants will be enrolled and can expect to be on study for up to 12 months.

Objective
Primary Objective

-To evaluate the safety and tolerability of INCB081776 in combination with pembrolizumab and standard palliative radiation therapy in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck.

Secondary Objectives

-To determine the preliminary efficacy of INCB081776 in combination with pembrolizumab plus palliative radiation therapy in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck. The irradiated lesion (lesion A) will not be included in the analysis.

Treatment Experimental: INCB081776/Pembrolizumab and RT for HNSCC
Cycle 1 of this clinical trial is 56 days in duration to allow for the systematic addition of each agent to the combination regimen. For cycle 2 and all subsequent cycles, the treatment cycle will be 21 days in length.

Key Eligibility Inclusion Criteria:

Participants must have histologic or cytologic evidence of head and neck squamous cell carcinoma (HNSCC) that is metastatic or recurrent and therefore considered incurable. Cutaneous skin squamous cell carcinomas located in the head and neck region are eligible after discussion with the Sponsor-Investigator.

Measurable disease that are considered non-amenable to surgery or other curative treatments or procedures, with at least 1 target lesion available for evaluation.



The preference is for measurable disease to be selected from a site that has not received any prior radiation or locoregional therapy. However, if a tumor lesion is situated in a previously irradiated area, or in an area subjected to other prior locoregional therapy, the lesion should demonstrate disease progression after the prior treatment.



Prior cancer treatment must be completed at least 14 days prior to enrollment (for chemotherapy, targeted small molecular therapy, or radiation therapy. Prior treatment with a monoclonal antibody must be completed at least 28 days prior to enrollment. Participants must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.

Participants must have two "index" tumors that meet the following criteria:



Index tumor A (lesion to receive palliative radiation therapy):



is deemed by the treating radiation oncologist to potentially benefit from palliative radiation

is at least 1 cm in longest dimension



Index tumor B (lesion to undergo biopsy):



Is deemed by the treating physician to be amenable to biopsy

Is at least 1 cm in longest dimension.

Participants must be willing to provide at least 2 research biopsies (up to 3 research biopsies) during the conduct of the study.

Note: If a subject is scheduled to have a baseline or on-study tumor biopsy, and the investigator believes that the tumor tissue cannot be obtained safely, then the biopsy may be omitted with approval by the Sponsor-Investigator. The participant may be replaced in order to enroll sufficient number of subjects for biomarker evaluation.

Note: Care should be taken to biopsy the same lesions for research samples. The preference is for the same lesion to be biopsied at all time points. If a lesion is no longer amenable for a research biopsy (for examples: due to a decrease in size, becomes inaccessible, is not safe/feasible for a biopsy), then an alternative lesion may be utilized with approval by the Sponsor-Investigator. Index tumor B (lesion to undergo biopsy) must not have received palliative radiation therapy during the study.



Participants must be willing to provide at least 2 collections of fresh research biopsies (up to 3 fresh research biopsies) during the conduct of this study.



Research biopsy #1 (baseline, mandatory). Archival tissue obtained since completion of last therapy may be used.

Research biopsy #2 (cycle 1 days 9-14, after treatment with INCB081776 but prior to pembrolizumab, mandatory)

Research biopsy #3 (cycle 1 day 37-56, after treatment with INCB081776, pembrolizumab and palliative RT). For participants who had baseline archival tissue collected (no baseline research biopsy was obtained), this fresh core biopsy is mandatory. For participants who underwent a fresh core research biopsy at baseline, this biopsy is optional.

Note: If a participant is scheduled to have an on-study tumor biopsy, and the investigator believes that the tumor tissue cannot be obtained safely, then the biopsy may be omitted after discussion with the Sponsor-Investigator. The participant may be replaced in order to enroll sufficient number of subjects for biomarker evaluation.

Note: Care should be taken to biopsy the same lesion for the on-treatment samples

Applicable Disease Sites
Esophagus; Head and Neck

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