Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Meta… (NCT05879484) | Clinical Trial Compass
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 range
18 Years – 120 Years
Sex
ALL
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.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Phase II: Disease control rate (DCR)
Timeframe: Study start until progression or 2 years after treatment initiation
2
Phase Ib: Safety of valemetostat in combination with pembrolizumab
Timeframe: Study start-30 days after last dose of study agents
3
Phase Ib: Recommended phase II dose (RP2D) of valemetostat in combination with pembrolizumab
. 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.
Exclusion criteria
. History of allergic reactions attributed to compounds of similar chemical or biologic composition to valemetostat or pembrolizumab used in the study.
. Prior curative radiation therapy or major surgery within 4 weeks or palliative radiation therapy within 2 weeks prior to the first dose of study drug(s).
. Prior systemic therapy (e.g., chemotherapy, immunomodulatory therapy, monoclonal antibody therapy, or investigational therapy) within 4 weeks, or 5 half-lives of the drug, whichever is longer, prior to the first dose of the study drug(s).
. History of previous treatment with EZH2 inhibition.
. Participants currently receiving any medications or substances that are moderate or strong inducers or moderate or strong inhibitors of cytochrome P450 (CYP3A).
. Participants currently receiving any medications or substances that are P-gp inhibitors (e.g., amiodarone, clarithromycin, diltiazem, erythromycin, ketoconazole, itraconazole, propafenone, quinidine, and verapamil).
. Consumption of foods and beverages that are strong CYP3A inhibitors or inducers (star fruit, Seville orange, Seville orange-containing foods and beverages, grapefruit, grapefruit-containing food or beverages) within 3 days prior to the first dose of study drug(s).
. Active immunosuppressive treatment equivalent to\>10 mg of prednisone daily. Note: Short-course systemic corticosteroids (e.g., prevention/treatment for transfusion reaction) or use for a non-cancer indication (e.g., adrenal replacement) is acceptable.