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

• ClinicalTrials.gov Identifier: NCT04193293
• Recruitment Status: Terminated
• First Posted: December 10, 2019
• Results First Posted: April 7, 2023
• Last Update Posted: April 7, 2023
• Sponsor: SecuraBio
• Information provided by (Responsible Party): SecuraBio

Tracking Information

• First Submitted Date: December 4, 2019
• First Posted Date: December 10, 2019
• Results First Submitted Date: March 14, 2023
• Results First Posted Date: April 7, 2023
• Last Update Posted Date: April 7, 2023
• Actual Study Start Date: June 1, 2020
• Actual Primary Completion Date: December 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2023)

• Stage 1: Number of Participants With Dose-limiting Toxicities [ Time Frame: 4 weeks or 28 days ]
• Stage 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 6 months ]
  Number of participants with TEAEs as assessed by the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) as a measure of safety and tolerability of duvelisib in combination with pembrolizumab.
• Stage 1 and 2: Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
  Proportion of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1).

Original Primary Outcome Measures (submitted: December 6, 2019)

• Stage 1 Unique Primary Objective: Safety and Tolerability of duvelisib in combination with pembrolizumab in subjects with R/M HNSCC [ Time Frame: 4 weeks or 28 days ]
  Number of participants with dose-limiting toxicities (DLTs)
• Stage 1 Unique Primary Objective: Safety and Tolerability of duvelisib in combination with pembrolizumab in subjects with R/M HNSCC [ Time Frame: 6 months ]
  Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.as a measure of safety and tolerability of duvelisib in combination with pembrolizumab
• Stage 1 & 2 Combined Primary Objective: Overall response rate (ORR) [ Time Frame: Up to 2 years ]
  Proportion of subjects achieving complete response (CR) or partial response (PR) according to RECIST v 1.1

Current Secondary Outcome Measures (submitted: March 14, 2023)

• Stage 1: ORR [ Time Frame: Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years) ]
  Proportion of participants achieving complete CR or PR according to RECIST v 1.1.
• Stage 1 and 2: Duration of Response (DOR) [ Time Frame: From first response until documented PD (up to 2 years) ]
  Time from response ≥ PR to documented disease progression according to RECIST v 1.1.
• Stage 1 and 2: Progression-free Survival (PFS) [ Time Frame: From start of treatment until documented PD or death (up to 2.5 years) ]
  Time from start of treatment to documented disease progression according to RECIST v 1.1, or death due to any cause.
• Stage 1 and 2: Overall Survival [ Time Frame: From start of treatment until death (up to 2.5 years) ]
  Time from start of treatment to death.
• Stage 1 and 2: Maximum Observed Concentration [Cmax] [ Time Frame: Up to 5 cycles (46 weeks) ]
  Pharmacokinetics (PK) parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and Population PK (POPPK) modeling.
• Stage 1 and 2: Area Under the Curve [AUC] [ Time Frame: Up to 5 cycles (46 weeks) ]
  PK parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and POPPK modeling.
• Stage 1 and 2: Number of Participants With TEAEs [ Time Frame: 24 months ]
  Number of participants with TEAEs as assessed by CTCAE v5.0.

Original Secondary Outcome Measures (submitted: December 6, 2019)

• Stage 1 Unique Secondary Objective: ORR [ Time Frame: Until documented PD, unacceptable toxicity, discontinuation criteria are met, withdrawal, or death. Up to 2 years. ]
  Proportion of subjects achieving complete CR or PR according to RECIST v 1.1
• Stage 1 & 2 Combined Secondary Objective: Duration of response (DOR) [ Time Frame: From first response until documented PD. Up to 2 years. ]
  Time from response ≥ PR to documented disease progression according to RECIST v 1.1
• Stage 1 & 2 Combined Secondary Objective: Progression-free survival (PFS) [ Time Frame: From start of treatment until documented PD or death. Assessed up to 2.5 years. ]
  Time from start of treatment to documented disease progression according to RECIST v 1.1, or death due to any cause
• Stage 1 & 2 Combined Secondary Objective: Overall survival (OS) [ Time Frame: From start of treatment until death. Assessed up to 2.5 years. ]
  Time from start of treatment to death
• Stage 1 & 2 Combined Secondary Objective: Maximum observed concentration [Cmax] [ Time Frame: Up to 5 cycles (46 weeks). ]
  PK parameters for duvelisib (and metabolite IPI-656) will be determined using bioanalytical data and Population PK (POPPK) modeling.
• Stage 1 & 2 Combined Secondary Objective: Area under the curve [AUC] [ Time Frame: Up to 5 cycles (46 weeks). ]
  PK parameters for duvelisib (and metabolite IPI-656) will be determined using bioanalytical data and POPPK modeling.
• Stage 1 & 2 Combined Secondary Objective: Safety and Tolerability of duvelisib in combination with pembrolizumab. [ Time Frame: 24 months ]
  Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Squamous Cell Carcinoma

Intervention

• Drug: Duvelisib
  Phosphoinositide 3-kinase (PI3K) Inhibitor
  Other Names:

  • VS-0145
  • Copiktra
• Biological: Pembrolizumab
  Immunotherapy (programmed cell death protein 1 [PD-1] inhibitor)
  Other Names:

  • PD-1 inhibitor
  • anti-PD-1
  • Keytruda

Study Arms

Experimental: Duvelisib + Pembrolizumab

Stage 1: Duvelisib twice daily (BID) for 1 week followed by combination therapy with duvelisib BID + pembrolizumab every 3 weeks (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.

Interventions:

• Drug: Duvelisib
• Biological: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 15, 2021): 2
• Original Estimated Enrollment (submitted: December 6, 2019): 30
• Actual Study Completion Date: December 10, 2020
• Actual Primary Completion Date: December 10, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04193293
• Other Study ID Numbers: VS-0145-130
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SecuraBio
• Original Responsible Party: Verastem, Inc.
• Current Study Sponsor: SecuraBio
• Original Study Sponsor: Verastem, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: SecuraBio
• Verification Date: March 2023