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

• Status: Suspended
• Trial end date: 2021-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: SecuraBio; Verastem, Inc.
• Treatments: Immune Checkpoint Inhibitors; Pembrolizumab

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