Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC

NCT ID: NCT05814666

Last Updated: 2024-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-30

Study Completion Date

2026-05-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HNSCC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Danvatirsen

Intervention Type DRUG

Danvatirsen is a STAT3 targeting drug.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2

Pembrolizumab

Pembrolizumab IV every 3 weeks after the Danvatirsen dose.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2

Interventions

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Danvatirsen

Danvatirsen is a STAT3 targeting drug.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2

Intervention Type DRUG

Other Intervention Names

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ISIS 481464 AZD9150 Keytruda

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Flamingo Therapeutics NV

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status RECRUITING

University of California Irvine (UCI)

Irvine, California, United States

Site Status RECRUITING

TMPN Hunt Cancer Care

Torrance, California, United States

Site Status RECRUITING

University of California Los Angeles

Westwood, Los Angeles, California, United States

Site Status RECRUITING

University of Colorado Hospital (UCH) Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status RECRUITING

Miami Cancer Institute

Miami, Florida, United States

Site Status RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

AMR Kansas City Oncology

Merriam, Kansas, United States

Site Status RECRUITING

University of Kansas Medical Center

Westwood, Kansas, United States

Site Status RECRUITING

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Site Status RECRUITING

University of Maryland Baltimore, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status NOT_YET_RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status RECRUITING

Morristown Medical Center

Morristown, New Jersey, United States

Site Status RECRUITING

Mount Sinai

New York, New York, United States

Site Status RECRUITING

Stony Brook Cancer Center

Stony Brook, New York, United States

Site Status RECRUITING

The Christ Hospital Cancer Center

Cincinnati, Ohio, United States

Site Status RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

University Hospitals Cleveland

Cleveland, Ohio, United States

Site Status RECRUITING

Prisma Health Cancer Institute

Greenville, South Carolina, United States

Site Status RECRUITING

UT Southwestern Medical Center/Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

Dong-A University Hospital

Busan, , South Korea

Site Status RECRUITING

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

Busan, , South Korea

Site Status RECRUITING

Gyeongsang National University Hospital

Jinju, , South Korea

Site Status RECRUITING

Korea University Medical Center (KUMC)

Seoul, , South Korea

Site Status RECRUITING

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

Seoul, , South Korea

Site Status RECRUITING

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

Leeds, , United Kingdom

Site Status RECRUITING

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status RECRUITING

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

London, , United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

East and North Hertfordshire NHS Trust, Lister Hospital

Northwood, Middlesex, , United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

Surry, , United Kingdom

Site Status RECRUITING

Countries

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United States South Korea United Kingdom

Central Contacts

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Flamingo Therapeutics

Role: CONTACT

Phone: 484 482 0007

Email: [email protected]

Facility Contacts

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Study Coordinator

Role: primary

Clinical Research Manager

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Study Coordinator

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Site Manager

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Project Manager

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Study Coordinator

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Study Coordinator

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Site Manager

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Study Coordinator

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Clinical Trials Manager

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Research Nurse

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Operations Manager

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Study Coordinator

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Site Manager

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Study Coordinator

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Study Coordinator, 82-10-8843-0031

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Study Coordinator

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Research Manager

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Other Identifiers

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FLM-6774-201

Identifier Type: -

Identifier Source: org_study_id