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NCT05814666 | RECRUITING | HNSCC

Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC
Sponsor:

Flamingo Therapeutics NV

Brief Summary:

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 or disease

HNSCC

Intervention/treatment

Danvatirsen

Pembrolizumab

Phase

PHASE2

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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 81 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : An Open-Label, Phase II, Randomized, Controlled Study of Danvatirsen Plus Pembrolizumab Compared to Pembrolizumab Alone in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
Actual Study Start Date : 2023-05-30
Estimated Primary Completion Date : 2025-05-30
Estimated Study Completion Date : 2026-05-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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.
Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC

Location Details

NCT05814666

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Arizona

The University of Arizona Cancer Center

Tucson, Arizona, United States, 85719

RECRUITING

United States, California

University of California Irvine (UCI)

Irvine, California, United States, 92617

RECRUITING

United States, California

TMPN Hunt Cancer Care

Torrance, California, United States, 90505

RECRUITING

United States, California

University of California Los Angeles

Westwood, California, United States, 90024

RECRUITING

United States, Colorado

University of Colorado Hospital (UCH) Anschutz Cancer Pavilion

Aurora, Colorado, United States, 80045

RECRUITING

United States, Florida

Miami Cancer Institute

Miami, Florida, United States, 33176

RECRUITING

United States, Georgia

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

RECRUITING

United States, Illinois

University of Illinois Cancer Center

Chicago, Illinois, United States, 60612

RECRUITING

United States, Kansas

AMR Kansas City Oncology

Merriam, Kansas, United States, 66204

RECRUITING

United States, Kansas

University of Kansas Medical Center

Westwood, Kansas, United States, 66205

RECRUITING

United States, Louisiana

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States, 70809

NOT YET RECRUITING

United States, Maryland

University of Maryland Baltimore, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

RECRUITING

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89169

RECRUITING

United States, New Jersey

Morristown Medical Center

Morristown, New Jersey, United States, 07960

RECRUITING

United States, New York

Mount Sinai

New York, New York, United States, 10029

RECRUITING

United States, New York

Stony Brook Cancer Center

Stony Brook, New York, United States, 11794

RECRUITING

United States, Ohio

The Christ Hospital Cancer Center

Cincinnati, Ohio, United States, 45219

RECRUITING

United States, Ohio

University of Cincinnati Medical Center

Cincinnati, Ohio, United States, 45229

RECRUITING

United States, Ohio

University Hospitals Cleveland

Cleveland, Ohio, United States, 44106

RECRUITING

United States, South Carolina

Prisma Health Cancer Institute

Greenville, South Carolina, United States, 29605

RECRUITING

United States, Texas

UT Southwestern Medical Center/Simmons Comprehensive Cancer Center

Dallas, Texas, United States, 75390

RECRUITING

Korea, Republic of,

Dong-A University Hospital

Busan, Korea, Republic of, 49201

RECRUITING

Korea, Republic of,

Kosin University College of Medicine - Kosin University Gospel Hospital (KUGH)

Busan, Korea, Republic of, 602-702

RECRUITING

Korea, Republic of,

Gyeongsang National University Hospital

Cries, Korea, Republic of, 52727

RECRUITING

Korea, Republic of,

Korea University Medical Center (KUMC)

Seoul, Korea, Republic of, 02841

RECRUITING

Korea, Republic of,

The Catholic University of Korea - Eunpyeong St. Mary's Hospital

Seoul, Korea, Republic of,

RECRUITING

United Kingdom,

Saint James's University Hospital (SJUH) - St James's Institute of Oncology

Leeds, United Kingdom,

RECRUITING

United Kingdom,

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom,

RECRUITING

United Kingdom,

Barts Health MHS Trust (Barts and The London NHS Trust) - St Bartholomew's (Barts) Hospital

London, United Kingdom, Ec1a 7be

RECRUITING

United Kingdom,

The Royal Marsden NHS Foundation Trust

London, United Kingdom, Jaya Taj

RECRUITING

United Kingdom,

East and North Hertfordshire NHS Trust, Lister Hospital

Northwood, Middlesex, United Kingdom, HA6 2RN

RECRUITING

United Kingdom,

The Royal Marsden NHS Foundation Trust

Surry, United Kingdom, SM2 5pt