WithdrawnPhase 1/2

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

Stopped: Study was never opened for enrollment as the CRADA was never executed

United States0Started 2025-07-09

Plain-language 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.

Who can participate

Age range18 Years – 120 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Participants must have a diagnosis of one of the following types of cancer:
✓Histologically or cytologically confirmed locoregionally recurrent or metastatic (R/M) human papillomavirus (HPV)-negative\* or -positive\* squamous cell carcinoma of the head and neck: oral cavity, tonsil, pharynx, hypopharynx, larynx. Note: Nasopharyngeal carcinoma and cutaneous squamous cell carcinoma (SCC) are excluded.
✓Histologically or cytologically confirmed R/M sinonasal carcinomas of the head and neck.
✓Histologically confirmed R/M squamous non-small cell lung cancer (NSCLC).
✓Histologically or cytologically confirmed locoregionally R/M HPV-negative\* squamous cell carcinoma of the head and neck: oral cavity, tonsil, pharynx, hypopharynx, larynx. Note: Nasopharyngeal carcinoma and cutaneous SCC are excluded.
✓. PD-L1 combined positive score (CPS) \>= 1, confirmed by Food and Drug Administration (FDA) approved 22C3 PharmDx test.
✓. Phase Ib only: Participants may be na(SqrRoot) ve or refractory to pembrolizumab or other PD- L1/PD-1 checkpoint inhibitors and may have had any number of lines of systemic therapy.
✓. Phase II only: Participants must be pembrolizumab-naive and not have received PD- L1/PD-1 checkpoint inhibitors and must not have had prior lines of systemic chemotherapy or immunotherapy for recurrent or metastatic HNSCC.

What they're measuring

Phase II: Disease control rate (DCR)

Timeframe: Study start until progression or 2 years after treatment initiation

Phase Ib: Safety of valemetostat in combination with pembrolizumab

Timeframe: Study start-30 days after last dose of study agents

Phase Ib: Recommended phase II dose (RP2D) of valemetostat in combination with pembrolizumab

Timeframe: 42 days

Trial details

NCT IDNCT05879484

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2025-07-09

View on ClinicalTrials.gov More Sinonasal Cancer trials

Plain-language summary

Who can participate

Age range18 Years – 120 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Participants must have a diagnosis of one of the following types of cancer:
✓Histologically or cytologically confirmed locoregionally recurrent or metastatic (R/M) human papillomavirus (HPV)-negative\* or -positive\* squamous cell carcinoma of the head and neck: oral cavity, tonsil, pharynx, hypopharynx, larynx. Note: Nasopharyngeal carcinoma and cutaneous squamous cell carcinoma (SCC) are excluded.
✓Histologically or cytologically confirmed R/M sinonasal carcinomas of the head and neck.
✓Histologically confirmed R/M squamous non-small cell lung cancer (NSCLC).
✓Histologically or cytologically confirmed locoregionally R/M HPV-negative\* squamous cell carcinoma of the head and neck: oral cavity, tonsil, pharynx, hypopharynx, larynx. Note: Nasopharyngeal carcinoma and cutaneous SCC are excluded.
✓. PD-L1 combined positive score (CPS) \>= 1, confirmed by Food and Drug Administration (FDA) approved 22C3 PharmDx test.
✓. Phase Ib only: Participants may be na(SqrRoot) ve or refractory to pembrolizumab or other PD- L1/PD-1 checkpoint inhibitors and may have had any number of lines of systemic therapy.
✓. Phase II only: Participants must be pembrolizumab-naive and not have received PD- L1/PD-1 checkpoint inhibitors and must not have had prior lines of systemic chemotherapy or immunotherapy for recurrent or metastatic HNSCC.

What they're measuring

Phase II: Disease control rate (DCR)

Timeframe: Study start until progression or 2 years after treatment initiation

Phase Ib: Safety of valemetostat in combination with pembrolizumab

Timeframe: Study start-30 days after last dose of study agents

Phase Ib: Recommended phase II dose (RP2D) of valemetostat in combination with pembrolizumab

Timeframe: 42 days

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria