Purpose

Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic (R/M) HNSCC. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Must have given written informed consent (signed and dated). 2. Aged ≥18 years at the time of informed consent. 3. Recurrent/metastatic histologically or cytologically proven squamous cell carcinoma of the head and neck that is considered incurable by local therapy. Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. 4. Presence of measurable tumor per RECIST v1.1 criteria. 5. Detectable PD-L1 expression in tumor, defined as CPS ≥1 determined by a FDA or national regulatory agency of the country in which the patient resides.-approved test. 6. Baseline fresh tumor biopsy or archival specimen. 7. ECOG performance status of 0 or 1. 8. Adequate organ function within 10 days of study treatment, 9. Oxygen saturation on room air ≥92% by pulse oximetry. 10. Females must be non-pregnant and non-lactating and either be postmenopausal or agree to adequate birth control. 11. Males must be surgically sterile or agree to adequate birth control. 12. Has an estimated life expectancy of at least 3 months. 13. Has recovered from all complications or surgery and all toxicities of prior therapy

Exclusion Criteria

  1. Prior therapy for metastatic HNSCC. 2. Has disease suitable for local therapy with curative intent. 3. Primary tumor of the nasopharynx. 4. Has received prior therapy with an anti-programmed death 1 (PD-1), anti PD L1, or anti-programmed death-ligand-2 (PD-L2). 5. Radiation therapy (or other non-systemic therapy) within 2 weeks of Day 1 of study treatment. 6. Known autoimmune disease that has required systemic treatment 7. Known immunodeficiency or receiving systemic steroid therapy that would be the equivalent of >10 mg prednisone daily 8. Prior allogeneic tissue/solid organ transplant. 9. Has significant cardiovascular disease 10. Has received a live vaccine within 30 days 11. Active infection requiring systemic antiviral or antimicrobial therapy 12. History of (non-infectious) pneumonitis that required steroids or current pneumonitis. 13. History of other malignancies 14. Active HIV infection except patients who are currently stable on antiretroviral therapy for at least 4 weeks 15. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 16. Treated or untreated parenchymal brain metastases or leptomeningeal disease. 17. Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of investigational agent (if known), whichever is longer. 18. Hypersensitivity to any component of danvatirsen or pembrolizumab.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Danvatirsen plus pembrolizumab
Danvatirsen dosing: Week 1: Danvatirsen intravenously (IV) on Days 1, 3, and 5 Week 2 and subsequent weeks: Danvatirsen IV weekly Pembrolizumab dosing: Pembrolizumab every 3 weeks after the Danvatirsen dose.
  • Drug: Danvatirsen
    Danvatirsen is a STAT3 targeting drug.
    Other names:
    • ISIS 481464
    • AZD9150
  • Drug: Pembrolizumab
    Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2
    Other names:
    • Keytruda
Active Comparator
Pembrolizumab
Pembrolizumab IV every 3 weeks after the Danvatirsen dose.
  • Drug: Pembrolizumab
    Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2
    Other names:
    • Keytruda

Recruiting Locations

University of Kansas Medical Center
Westwood, Kansas 66205
Contact:
Project Manager
913-574-2854

More Details

Status
Recruiting
Sponsor
Flamingo Therapeutics NV

Study Contact

Flamingo Therapeutics
484 482 0007
clinical@flamingotx.com

Detailed Description

This is a multicenter, open-label, Phase II, randomized, controlled study to determine the efficacy, safety, and other indicators of clinical and biological activity of the combination of danvatirsen and pembrolizumab as first-line treatment for R/M HNSCC. After providing informed consent, patients will be assessed for eligibility during the screening phase of the study. All patients must be willing and able to provide a formalin fixed paraffin-embedded (FFPE) archival or fresh tumor sample collected during the screening period; a fresh biopsy is preferred if safe and feasible to obtain and consented to by the patient. Following the screening period, eligible patients will be randomized in a 2:1 ratio to danvatirsen + pembrolizumab or pembrolizumab monotherapy, respectively. Patients will receive treatment in 21-day cycles. Patients assigned to the pembrolizumab monotherapy arm will receive treatment until a criterion for discontinuation is met or a maximum of 24 months of treatment. Patients assigned to combination therapy will receive both treatments until a criterion for discontinuation is met or the patient has received a maximum of 24 months of treatment, after which they may remain on danvatirsen monotherapy. Patients in both treatment arms will have radiologic tumor assessments every 6 weeks (±1 week), regardless of treatment delays, until objective disease progression, initiation of new anticancer treatment, death, withdrawal of consent, or end of study, whichever occurs first. All patients who discontinue study treatment for any reason will have a safety follow-up visit 30 days (+7 days) after the last dose of study treatment and a follow-up for AEs 90 days (+7 days) after the last dose of pembrolizumab. Patients will be followed for survival at 12 week (±7 days) intervals until death or withdrawal of consent, whichever occurs first. Survival follow-up will continue until at least 15 months after the last patient is randomized in the study.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.