Intervention: Duvelisib
Trial phase: Phase 1 | Phase 2
ATC code: L01EM04
SMILES: C[C@H](Nc1ncnc2[nH]cnc12)c1cc2cccc(Cl)c2c(=O)n1-c1ccccc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2
Group description: Stage 1: Duvelisib BID for 1 week followed by combination therapy with duvelisib BID + pembrolizumab q3w (Cycle 1 was 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 were 3 weeks).

Stage 2: Duvelisib BID + pembrolizumab q3w in 3-week cycles.
Eligibility criteria:
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