Tazemetostat and Pembrolizumab in Patients With Pembrolizumab- or Nivolumab-Resistant, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma

NCT04624113 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 202011174
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of the phase 1 portion of the trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat in combination with a fixed dose of pembrolizumab in patients with recurrent or metastatic (RM) head and neck cancer. The primary aim of the phase 2 portion of the trial is to establish the proportion of patients with pembrolizumab- or nivolumab-resistant, PD-L1 positive, RM head and neck squamous-cell carcinoma (HNSCC) who achieve an objective tumor response to tazemetostat and pembrolizumab.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose of tazemetostat in combination with a fixed dose of pembrolizumab (Phase I only)

  Completion of cycle 1 for all phase I participants (estimated to be 9 months)

• Objective response rate (ORR) assessed by iRECIST (Phase 2 only)

  -ORR: complete or partial response achieved as best response divided by those participants who have received a response evaluation (scan)

  Through completion of treatment (estimated to be 5 months)

Secondary Outcomes (4)

• Incidence of adverse events

  From start of treatment through 28 days post-treatment (estimated to be 6 months)

• Duration of response (DOR)

  Through completion of treatment (estimated to be 5 months)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 17 months)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 17 months)

Study Arms (2)

Phase I: Tazemetostat + Pembrolizumab

EXPERIMENTAL

* Cycle 1 over 5 weeks (35 days). Subsequent cycles over 3 weeks (21 days). * Tazemetostat tablet twice per day Days 1-35 of Cycle 1, then Days 1-21 of subsequent cycles. Dose of tazemetostat will depend on dose level assigned * Pembrolizumab 200mg intravenous Day 15 of Cycle 1, then Day 1 of subsequent cycles.

Drug: Tazemetostat; Drug: Pembrolizumab

Phase 2: Tazemetostat + Pembrolizumab

EXPERIMENTAL

* Cycle 1 over 5 weeks (35 days). Subsequent cycles over 3 weeks (21 days). * Tazemetostat tablet twice per day Days 1-35 of Cycle 1, then Days 1-21 of subsequent cycles. Dose of tazemetostat will depend of recommended phase 2 determined in Phase I portion of study. * Pembrolizumab 200mg intravenous Day 15 of Cycle 1, then Day 1 of subsequent cycles.

Drug: Tazemetostat; Drug: Pembrolizumab

Interventions

Tazemetostat DRUG

Epizyme will supply the study agent, which will be provided free of charge to the patient.

Also known as: Tazverik

Phase 2: Tazemetostat + Pembrolizumab; Phase I: Tazemetostat + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is commercially available

Also known as: Keytruda

Phase 2: Tazemetostat + Pembrolizumab; Phase I: Tazemetostat + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis:
• Phase 1 specific: recurrent or metastatic head and neck cancer, inclusive of cancers that originate in the head and neck, except central nervous system (CNS) cancers.
• Phase 2 specific: recurrent or metastatic head and neck squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx.
• Disease Evaluation:
• Phase 1 specific: Measurable or evaluable disease
• Phase 2 specific: Measurable disease per RECIST. Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Phase 2 specific: Progression of disease, as assessed by RECIST, that occurred on prior pembrolizumab or nivolumab (given alone or with other therapy) in the last 6 months.
• Phase 2 specific: PD-L1 positive (CPS ≥ 1 by IHC, 22C3 antibody) on archived tumor tissue. If CPS not available, tumors with PD-L1 TPS ≥ 1 are also eligible (but CPS should be performed in these cases).
• Incurable disease (defined as surgery and/or radiation is unable to offer curative potential), or ineligible for (or patient declined) local therapy.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 750/mcL
• Platelets ≥ 75,000/mcL
• Hemoglobin ≥ 9 g/L

You may not qualify if:

• Radiation, chemotherapy, or targeted therapy within 14 days of treatment start.
• Phase 2 specific: Prior therapy with an EZH2 inhibitor.
• Investigational therapy within 21 days of treatment start.
• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of disease.
• Has known active CNS metastases. Subjects with previously treated brain metastases may participate provided they are stable (without any evidence of progression by imaging 4 weeks prior to the first dose of study treatment and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and are on stable or tapering doses of steroids for at least 14 days prior to first dose of study treatment.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat, pembrolizumab, or other agents used in the study.
• Unable to swallow oral medication.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of treatment.
• Prior organ or allogeneic stem cell transplant.
• Has an active autoimmune disease (i.e. rheumatoid arthritis, lupus, Sjogren's syndrome) that has required IV or subcutaneous systemic treatment in the past 6 months (excluding Rituxan). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Epizyme, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

tazemetostat; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 10, 2020
• Study Start: April 14, 2021
• Primary Completion: August 9, 2022
• Study Completion: February 17, 2024
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)