Clinical Trials /

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

NCT04624113

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tazemetostat and Pembrolizumab in Patients With Pembrolizumab- or Nivolumab-Resistant, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma
  • Official Title: Tazemetostat and Pembrolizumab in Patients With Pembrolizumab- or Nivolumab-Resistant, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A Phase 1-2 Trial

Clinical Trial IDs

  • ORG STUDY ID: 202011174
  • NCT ID: NCT04624113

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
TazemetostatTazverikPhase 2: Tazemetostat + Pembrolizumab
PembrolizumabKeytrudaPhase 2: Tazemetostat + Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I: Tazemetostat + PembrolizumabExperimentalCycle 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.
  • Tazemetostat
  • Pembrolizumab
Phase 2: Tazemetostat + PembrolizumabExperimentalCycle 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.
  • Tazemetostat
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  Total bilirubin ≤ 1.5 x IULN

               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

               -  Serum creatinine <1.5x ULN or Creatinine clearance ≥ 50 mL/min by Cockcroft-Gault

          -  The effects of tazemetostat on the developing human fetus are unknown. For this reason
             and because histone methyltransferase (HMT) agents are known to be teratogenic, women
             of childbearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control, abstinence) prior to study entry, for the duration
             of study participation, and for 6 months after the last day of treatment. Should a
             woman become pregnant or suspect she is pregnant while participating in this study,
             she must inform her treating physician immediately. Men treated or enrolled on this
             protocol must also agree to use adequate contraception prior to the study, for the
             duration of the study, and for 6 months after last day of treatment.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  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.

          -  Receiving systemic corticosteroid therapy (in doses exceeding 10 mg daily of
             prednisone equivalent) within 7 days prior to the first dose of treatment. A history
             of severe autoimmune disorder requiring high-dose corticosteroid treatment due to
             prior PD-1 inhibitor is an exclusion criterion.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase 2 dose of tazemetostat in combination with a fixed dose of pembrolizumab (Phase I only)
Time Frame:Completion of cycle 1 for all phase I participants (estimated to be 9 months)
Safety Issue:
Description:-ORR: complete or partial response achieved as best response divided by those participants who have received a response evaluation (scan)

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:From start of treatment through 28 days post-treatment (estimated to be 6 months)
Safety Issue:
Description:-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
Measure:Duration of response (DOR)
Time Frame:Through completion of treatment (estimated to be 5 months)
Safety Issue:
Description:-Response duration will be measured from the time measurement criteria for CR/PR or iCR/iPR (whichever is first recorded) are first met until the first date that recurrent or PD is objectively documented, taking as reference the smallest measurements recorded on study (including baseline).
Measure:Progression-free survival (PFS)
Time Frame:Through completion of follow-up (estimated to be 17 months)
Safety Issue:
Description:-PFS is defined as the time from date of study enrollment to disease progression or death from any cause, whichever occurs first. The patients alive, without progression, are censored at the last follow-up.
Measure:Overall survival (OS)
Time Frame:Through completion of follow-up (estimated to be 17 months)
Safety Issue:
Description:-OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

February 16, 2021