Clinical trial NCT04193293: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Squamous Cell Carcinoma of the Head and Neck
Head and Neck Cancer
PI3K-δ,γ
PI3K Inhibitor
Lead sponsor: SecuraBio
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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

Primary outcomes:
measure: Stage 1: Number of Participants With Dose-limiting Toxicities
timeFrame: 4 weeks or 28 days
measure: Stage 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 6 months
measure: Stage 1 and 2: Overall Response Rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Stage 1: ORR
timeFrame: Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years)
measure: Stage 1 and 2: Duration of Response (DOR)
timeFrame: From first response until documented PD (up to 2 years)
measure: Stage 1 and 2: Progression-free Survival (PFS)
timeFrame: From start of treatment until documented PD or death (up to 2.5 years)
measure: Stage 1 and 2: Overall Survival
timeFrame: From start of treatment until death (up to 2.5 years)
measure: Stage 1 and 2: Maximum Observed Concentration [Cmax]
timeFrame: Up to 5 cycles (46 weeks)
measure: Stage 1 and 2: Area Under the Curve [AUC]
timeFrame: Up to 5 cycles (46 weeks)
measure: Stage 1 and 2: Number of Participants With TEAEs
timeFrame: 24 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
References: