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

Lung Cancer Clinical Trial

Official title: A Phase Ib/II Multicenter 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

Status Not yet recruiting

Clinical Trial Summary

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. These cancers have different causes, with smoking/tobacco exposure and human papilloma virus infection being the most common. . When HNSCC occurs in people who are not infected with HPV, the cancers are more likely to return after treatment; when this happens, overall survival is only about 10 months, thus better treatments are needed. Objective: To test a combination treatment using 2 drugs (valemetostat and pembrolizumab) in people with HNSCC. Phase 1b of the study will determine a recommended dose of the 2 drugs and evaluate how safe the combination is.; this will include patients with HPV-positive and HPV-negative HNSCC, as well as squamous cell NSCLC that have progressed on anti-PD-1/anti-PD-L1 therapies.Phase II will determine how effective the combination is and will focus on patients with HPV-negative HNSCC. Eligibility: People aged 18 years and older with HPV-negative HNSCC, sinonasal carcinoma of the head and neck, or squamous non-small cell lung cancer (NSCLC). Design: Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They will have imaging scans. They may have a biopsy: A small sample of tissue will be removed from the tumor. Treatment will be given in 21-day cycles. Pembrolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will receive pembrolizumab on the first day of each cycle. Valemetostat is a tablet taken by mouth. Participants will take the tablet once a day at home. They will record the date and time of each dose in a diary. They will also write down any adverse effects they experience. Participants may remain in the study up to 2 years.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Squamous Cell Carcinoma
• Lung Cancer
• Lung Neoplasms
• Sinonasal Cancer
• Squamous Cell Carcinoma of Head and Neck
• Squamous Non-small Cell Lung Cancer

• NCT number: NCT05879484
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Christine A Feierabend
• Phone: (240) 357-9346
• Email: chris.feierabend@nih.gov
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 5, 2024
• Completion date: July 1, 2027