a study of duvelisib in combination with pembrolizumab in head and neck cancer

Conditions: Head and Neck Squamous Cell Carcinoma

Summary: this study was designed to assess the safety and preliminary efficacy of duvelisib in combination with pembrolizumab in participants with recurrent or metastatic (r/m) head and neck squamous cell carcinoma (hnscc).

this was a non-randomized, open-label phase 1b/2 study designed to evaluate safety, tolerability, and preliminary efficacy of duvelisib in combination with pembrolizumab in participants with r/m hnscc who were eligible for pembrolizumab monotherapy based on the current pembrolizumab prescribing information.

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

Keywords: squamous cell carcinoma of the head and neck head and neck cancer pi3k-δ,γ pi3k inhibitor