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

Inclusion Criteria

• Eastern Cooperative Oncology Group 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 was 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 Response Evaluation Criteria in Solid Tumors version 1.1
• For stage 1 only: Must have had at least 1 other lesion that could be biopsied and willing to undergo a pretreatment and on-treatment biopsy of the available tumor lesion
• For stage 1 only: Must have been 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 ≥ 1.5 × 10^9/liter (L)
• Platelet count ≥ 100 × 10^9/L
• Hemoglobin level ≥ 9.0 grams/deciliter (dL)
• A serum creatinine level < 1.5 milligrams/dL, or
• Estimated creatinine clearance value ≥ 60 milliliters/minute (as determined by the Cockcroft-Gault method) for participants with creatinine levels > 1.5 × institutional upper limit of normal (ULN)
• Total bilirubin level ≤ 1.5 × ULN (exception: participants with Gilbert's Syndrome may have a bilirubin level > 1.5 × ULN)
• Aspartate aminotransaminase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum pyruvic transaminase levels ≤ 2.5 × ULN or ≤ 5 × ULN in participants with liver metastases
• International normalized ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, unless participant was receiving anticoagulant therapy in which case PT or aPTT must have been 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 programmed cell death ligand 1 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 or Epstein-Barr virus infection; history of or known human immunodeficiency virus 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. 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, HSV, or VZV at screening
• Any active gastrointestinal dysfunction interfering with the participant's ability to be administered oral medications
• Known active central nervous system metastases and/or carcinomatous meningitis
• QT interval > 500 milliseconds (except for participants with a right or left bundle branch block)
• New York Heart Association Class III or IV congestive heart failure