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

NCT04193293 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: VS-0145-130
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (3)

• Stage 1: Number of Participants With Dose-limiting Toxicities

  4 weeks or 28 days

• Stage 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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.

  6 months

• Stage 1 and 2: Overall Response Rate (ORR)

  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).

  Up to 2 years

Secondary Outcomes (7)

• Stage 1: ORR

  Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years)

• Stage 1 and 2: Duration of Response (DOR)

  From first response until documented PD (up to 2 years)

• Stage 1 and 2: Progression-free Survival (PFS)

  From start of treatment until documented PD or death (up to 2.5 years)

• Stage 1 and 2: Overall Survival

  From start of treatment until death (up to 2.5 years)

• Stage 1 and 2: Maximum Observed Concentration [Cmax]

  Up to 5 cycles (46 weeks)

Study Arms (1)

Duvelisib + Pembrolizumab

EXPERIMENTAL

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.

Drug: Duvelisib; Biological: Pembrolizumab

Interventions

Duvelisib DRUG

Phosphoinositide 3-kinase (PI3K) Inhibitor

Also known as: VS-0145, Copiktra

Duvelisib + Pembrolizumab

Pembrolizumab BIOLOGICAL

Immunotherapy (programmed cell death protein 1 \[PD-1\] inhibitor)

Also known as: PD-1 inhibitor, anti-PD-1, Keytruda

Duvelisib + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SecuraBio: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

duvelisib; pembrolizumab; Immune Checkpoint Inhibitors; spartalizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Limitations and Caveats

The study was terminated early by the Sponsor due to low enrollment. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.

Results Point of Contact

• Title: Beth Gregory, PharmD, MBA
• Organization: Secura Bio, Inc.

bgregory@securabio.com

1-702-254-0011

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: December 10, 2019
• Study Start: June 1, 2020
• Primary Completion: December 10, 2020
• Study Completion: December 10, 2020
• Last Updated: September 21, 2023
• Results First Posted: April 7, 2023

Record last verified: 2023-09

Locations

US (1)