Clinical Trials /

A Study of Duvelisib in Combination With Pembrolizumab in Head and Neck Cancer

NCT04193293

Description:

This study will assess the safety and preliminary efficacy of duvelisib in combination with pembrolizumab in subjects with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Duvelisib in Combination With Pembrolizumab in Head and Neck Cancer
  • Official Title: A Phase 1b/2 Study of Duvelisib in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Cancer

Clinical Trial IDs

  • ORG STUDY ID: VS-0145-130
  • NCT ID: NCT04193293

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
duvelisibVS-0145, CopiktraDuvelisib BID + Pembrolizumab q3w
pembrolizumabPD-1 inhibitor, anti-PD-1, KeytrudaDuvelisib BID + Pembrolizumab q3w

Purpose

This study will assess the safety and preliminary efficacy of duvelisib in combination with pembrolizumab in subjects with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Detailed Description

      This is a multicenter, non-randomized, open-label Phase 1b/2 study designed to evaluate
      safety and tolerability and preliminary efficacy of duvelisib in combination with
      pembrolizumab in subjects with R/M HNSCC who are eligible for pembrolizumab monotherapy based
      on the current pembrolizumab prescribing information.
    

Trial Arms

NameTypeDescriptionInterventions
Duvelisib BID + Pembrolizumab q3wExperimentalStage 1: Duvelisib BID for 1 week followed by combination therapy with duvelisib BID + pembrolizumab q3w. (Cycle 1 will be 4 weeks consisting of the 1-week duvelisib monotherapy lead-in period followed by 1 dose of pembrolizumab in combination with 3 additional weeks of continuous dosing of duvelisib. Subsequent cycles will be 3 weeks .) Stage 2: Duvelisib BID + pembrolizumab q3w in 3 week cycles.
  • duvelisib
  • pembrolizumab

Eligibility Criteria

        Inclusion Criteria

          -  Age ≥ 18 years, ECOG performance status ≤ 1

          -  Histologically or cytologically-confirmed diagnosis of recurrent or metastatic head
             and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or
             larynx that is considered incurable by local therapies

          -  Eligible for pembrolizumab monotherapy based on the current prescribing information
             for pembrolizumab (Keytruda 2019)

          -  Must have had 0 to 2 prior therapies for R/M HNSCC.

          -  At least 1 measurable lesion (which has not been previously irradiated) according to
             RECIST v 1.1

          -  For stage 1 only: Must have at least 1 other lesion that can be biopsied and willing
             to undergo a pretreatment and on-treatment biopsy of the available tumor lesion

          -  For stage 1 only: Must be willing to undergo a pretreatment and on-treatment biopsy of
             the available tumor lesion

          -  Adequate organ function defined by the following laboratory parameters:

          -  Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

          -  Platelet count ≥ 100 × 109/L

          -  Hemoglobin level ≥ 9.0 g/dL

          -  A serum creatinine level < 1.5 mg/dL, or

          -  Estimated creatinine clearance value ≥ 60 mL/min (as determined by the Cockcroft-Gault
             method) for subjects with creatinine levels > 1.5 × institutional upper limit of
             normal (ULN)

          -  Total bilirubin level ≤ 1.5 × ULN (exception: subjects with Gilbert's Syndrome may
             have a bilirubin level > 1.5 × ULN)

          -  Aspartate aminotransaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and
             alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) levels ≤ 2.5 × ULN or
             ≤ 5 × ULN in subjects with liver metastases

          -  International normalized ratio (INR) or prothrombin time (PT) and activated partial
             thromboplastin time (aPTT) ≤ 1.5 × ULN, unless subject is receiving anticoagulant
             therapy in which case PT or aPTT must be within therapeutic range of intended use of
             anticoagulants

        Exclusion Criteria

          -  Previously treated with 3 or more systemic regimens given for recurrent and/or
             metastatic disease

          -  Received anticancer treatment, major surgery, or any investigational drug within 30
             days or 5 half-lives, whichever is shorter, before the start of study intervention

          -  Received radiation therapy within 14 days before the start of study intervention,
             including, in addition (if necessary), the timeframe for resolution of any actual or
             anticipated toxicities from such radiation; Palliative radiation is allowed if > 7
             days and any toxicity is ≤ Grade 1

          -  Previous treatment with a PI3K, PD-1 or PD-L1 inhibitor

          -  Have received organ or allogenic bone marrow or peripheral blood stem cell transplant

          -  History of drug-induced colitis or drug-induced pneumonitis; history or concurrent
             condition of interstitial lung disease of any severity and/or severely impaired lung
             function; tuberculosis treatment within 2 years prior to the start of study
             intervention; chronic liver disease or veno-occlusive disease/sinusoidal obstruction
             syndrome

          -  Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection; history of or
             known human immunodeficiency virus (HIV) infection

          -  Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment
             for systemic bacterial, fungal, or viral infection

          -  Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV),
             or herpes zoster (VZV) at screening

          -  Concurrent administration of medications or foods that are strong inhibitors or
             inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start
             of study intervention Received a live or live attenuated vaccine within 6 weeks of
             first dose of duvelisib

          -  Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV),
             or herpes zoster (VZV) at screening

          -  Any active gastrointestinal dysfunction interfering with the subject's ability to be
             administered oral medications

          -  Known active central nervous system metastases and/or carcinomatous meningitis

          -  QT interval > 500 ms (except for subjects with a right or left bundle branch block)

          -  New York Heart Association Class III or IV congestive heart failure
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Stage 1: Number of participants with dose-limiting toxicities (DLTs)
Time Frame:4 weeks or 28 days
Safety Issue:
Description:Number of participants with dose-limiting toxicities (DLTs)

Secondary Outcome Measures

Measure:Stage 1 Unique Secondary Objective: ORR
Time Frame:Until documented PD, unacceptable toxicity, discontinuation criteria are met, withdrawal, or death. Up to 2 years.
Safety Issue:
Description:Proportion of subjects achieving complete CR or PR according to RECIST v 1.1
Measure:Stage 1 & 2 Combined Secondary Objective: Duration of response (DOR)
Time Frame:From first response until documented PD. Up to 2 years.
Safety Issue:
Description:Time from response ≥ PR to documented disease progression according to RECIST v 1.1
Measure:Stage 1 & 2 Combined Secondary Objective: Progression-free survival (PFS)
Time Frame:From start of treatment until documented PD or death. Assessed up to 2.5 years.
Safety Issue:
Description:Time from start of treatment to documented disease progression according to RECIST v 1.1, or death due to any cause
Measure:Stage 1 & 2 Combined Secondary Objective: Overall survival (OS)
Time Frame:From start of treatment until death. Assessed up to 2.5 years.
Safety Issue:
Description:Time from start of treatment to death
Measure:Stage 1 & 2 Combined Secondary Objective: Maximum observed concentration [Cmax]
Time Frame:Up to 5 cycles (46 weeks).
Safety Issue:
Description:PK parameters for duvelisib (and metabolite IPI-656) will be determined using bioanalytical data and Population PK (POPPK) modeling.
Measure:Stage 1 & 2 Combined Secondary Objective: Area under the curve [AUC]
Time Frame:Up to 5 cycles (46 weeks).
Safety Issue:
Description:PK parameters for duvelisib (and metabolite IPI-656) will be determined using bioanalytical data and POPPK modeling.
Measure:Stage 1 & 2: Number of participants with treatment-emergent adverse events
Time Frame:24 months
Safety Issue:
Description:Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Verastem, Inc.

Trial Keywords

  • Squamous Cell Carcinoma of the Head and Neck
  • Head and Neck Cancer
  • PI3K-δ,γ
  • PI3K Inhibitor

Last Updated

February 25, 2020