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

• ClinicalTrials.gov Identifier: NCT04193293
• Recruitment Status: Suspended
• First Posted: December 10, 2019
• Last Update Posted: March 17, 2021
• Sponsor: SecuraBio
• Information provided by (Responsible Party): SecuraBio

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Head and Neck Squamous Cell Carcinoma	Drug: duvelisib; Biological: pembrolizumab	Phase 1; Phase 2

Detailed Description:

This is a multicenter, non-randomized, open-label Phase 1b/2 study designed to evaluate safety and tolerability and preliminary efficacy of duvelisib in combination with pembrolizumab in subjects with R/M HNSCC who are eligible for pembrolizumab monotherapy based on the current pembrolizumab prescribing information.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 25, 2020
• Actual Primary Completion Date: November 15, 2020
• Estimated Study Completion Date: April 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Duvelisib BID + Pembrolizumab q3w; Stage 1: Duvelisib BID for 1 week followed by combination therapy with duvelisib BID + pembrolizumab q3w. (Cycle 1 will be 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 will be 3 weeks .) Stage 2: Duvelisib BID + pembrolizumab q3w in 3 week cycles.

Drug: duvelisib; PI3K Inhibitor; Other Names: VS-0145; Copiktra; Biological: pembrolizumab; Immunotherapy (PD-1 inhibitor); Other Names: PD-1 inhibitor; anti-PD-1; Keytruda

Outcome Measures

Primary Outcome Measures :

1. Stage 1: Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: 4 weeks or 28 days ]
   Number of participants with dose-limiting toxicities (DLTs)
2. Stage 1: Number of participants with treatment-emergent adverse events. [ 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
3. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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.
6. 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.
7. Stage 1 & 2: Number of participants with treatment-emergent adverse events [ Time Frame: 24 months ]
   Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Pennsylvania

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

SecuraBio

Investigators

• Study Director: David Cohan, MD; SecuraBio Chief Medical Officer

More Information

• Responsible Party: SecuraBio
• ClinicalTrials.gov Identifier: NCT04193293
• Other Study ID Numbers: VS-0145-130
• First Posted: December 10, 2019
• Last Update Posted: March 17, 2021
• Last Verified: March 2021

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

Keywords provided by SecuraBio:

Squamous Cell Carcinoma of the Head and Neck; Head and Neck Cancer; PI3K-δ,γ; PI3K Inhibitor

Additional relevant MeSH terms:

Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Pembrolizumab; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action