A Study of Duvelisib in Combination With Pembrolizumab in Head and Neck Cancer
Study Details
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 |
|---|---|---|
|
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
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:
Biological: pembrolizumab
Immunotherapy (PD-1 inhibitor)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Stage 1: Number of participants with dose-limiting toxicities (DLTs) [4 weeks or 28 days]
Number of participants with dose-limiting toxicities (DLTs)
- Stage 1: Number of participants with treatment-emergent adverse events. [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) [Up to 2 years]
Proportion of subjects achieving complete response (CR) or partial response (PR) according to RECIST v 1.1
Secondary Outcome Measures
- Stage 1 Unique Secondary Objective: ORR [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) [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) [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) [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] [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] [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: Number of participants with treatment-emergent adverse events [24 months]
Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0
Eligibility Criteria
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)
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Must have had 0 to 2 prior therapies for R/M HNSCC.
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At least 1 measurable lesion (which has not been previously irradiated) according to RECIST v 1.1
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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
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For stage 1 only: Must be willing to undergo a pretreatment and on-treatment biopsy of the available tumor lesion
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Adequate organ function defined by the following laboratory parameters:
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Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
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Platelet count ≥ 100 × 109/L
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Hemoglobin level ≥ 9.0 g/dL
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A serum creatinine level < 1.5 mg/dL, or
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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)
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Total bilirubin level ≤ 1.5 × ULN (exception: subjects with Gilbert's Syndrome may have a bilirubin level > 1.5 × ULN)
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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
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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
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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
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Previous treatment with a PI3K, PD-1 or PD-L1 inhibitor
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Have received organ or allogenic bone marrow or peripheral blood stem cell transplant
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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
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Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection; history of or known human immunodeficiency virus (HIV) infection
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Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection
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Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
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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
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Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
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Any active gastrointestinal dysfunction interfering with the subject's ability to be administered oral medications
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Known active central nervous system metastases and/or carcinomatous meningitis
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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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
Sponsors and Collaborators
- SecuraBio
Investigators
- Study Director: David Cohan, MD, SecuraBio Chief Medical Officer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VS-0145-130