Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC

NCT05814666 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: FLM-6774-201
• Study Type: interventional
• Target: 69
• Locations: 3 countries
• Sites: 32

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.

Conditions

HNSCC

Outcome Measures

Primary Outcomes (1)

• Confirmed ORR

  Determine the ORR (Partial response \[PR\] + CR defined according to RECIST v1.1) as determined by the Investigator for the combination of danvatirsen and pembrolizumab compared with pembrolizumab alone

  Up to 18 months

Secondary Outcomes (12)

• Number of Participants With Adverse Events as Assessed by CTCAE v5.0

  Up to 18 months

• DOR

  Up to 18months

• DCR & CR Rate

  Up to 18months

• ORR in Tumors With CPS ≥20 and ≥ 50

  Up to 18months

• DOR in Tumors With CPS ≥20 and ≥50

  Up to 18months

Study Arms (2)

Danvatirsen plus pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Pembrolizumab

ACTIVE COMPARATOR

Pembrolizumab IV every 3 weeks

Drug: Pembrolizumab

Interventions

Danvatirsen DRUG

Danvatirsen is a STAT3 targeting drug.

Also known as: ISIS 481464, AZD9150

Danvatirsen plus pembrolizumab

Pembrolizumab DRUG

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

Also known as: Keytruda

Danvatirsen plus pembrolizumab; Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Must have given written informed consent (signed and dated).
• Aged ≥18 years at the time of informed consent.
• 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.
• Presence of measurable tumor per RECIST v1.1 criteria.
• 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.
• Baseline fresh tumor biopsy or archival specimen.
• ECOG performance status of 0 or 1.
• Adequate organ function within 10 days of study treatment,
• Oxygen saturation on room air ≥92% by pulse oximetry.
• Females must be non-pregnant and non-lactating and either be postmenopausal or agree to adequate birth control.
• Males must be surgically sterile or agree to adequate birth control.
• Has an estimated life expectancy of at least 3 months.
• Has recovered from all complications or surgery and all toxicities of prior therapy

You may not qualify if:

• Prior therapy for metastatic HNSCC.
• Has disease suitable for local therapy with curative intent.
• Primary tumor of the nasopharynx.
• Has received prior therapy with an anti-programmed death 1 (PD-1), anti PD L1, or anti-programmed death-ligand-2 (PD-L2).
• Radiation therapy (or other non-systemic therapy) within 2 weeks of Day 1 of study treatment.
• Known autoimmune disease that has required systemic treatment
• Known immunodeficiency or receiving systemic steroid therapy that would be the equivalent of \>10 mg prednisone daily
• Prior allogeneic tissue/solid organ transplant.
• Has significant cardiovascular disease
• Has received a live vaccine within 30 days
• Active infection requiring systemic antiviral or antimicrobial therapy
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• History of other malignancies
• Active HIV infection except patients who are currently stable on antiretroviral therapy for at least 4 weeks
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Sponsors & Collaborators

• Flamingo Therapeutics NV: lead

Study Sites (32)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of California Irvine (UCI)

Irvine, California, 92617, United States

Location

TMPN Hunt Cancer Care

Torrance, California, 90505, United States

Location

University of California Los Angeles

Westwood, Los Angeles, California, 90024, United States

Location

University of Colorado Hospital (UCH) Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

AMR Kansas City Oncology

Merriam, Kansas, 66204, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

Location

University of Maryland Baltimore, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

Location

The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland

Cleveland, Ohio, 44106, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

UT Southwestern Medical Center/Simmons Comprehensive Cancer Center

Dallas, Texas, 75390, United States

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

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

Busan, 602-702, South Korea

Location

Gyeongsang National University Hospital

Jinju, 52727, South Korea

Location

Korea University Medical Center (KUMC)

Seoul, 02841, South Korea

Location

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

Seoul, South Korea

Location

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

Leeds, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

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

London, EC1A 7BE, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

East and North Hertfordshire NHS Trust, Lister Hospital

Northwood, HA6 2RN, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

danvatirsen; pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Flamingo Therapeutics

clinical@flamingotx.com

484 482 0007

Study Officials

• Nabil Saba, MD

  Emory University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2023
• First Posted: April 18, 2023
• Study Start: May 30, 2023
• Primary Completion: August 14, 2025
• Study Completion: August 14, 2025
• Last Updated: January 30, 2026
• Results First Posted: January 30, 2026

Record last verified: 2025-12

Locations

US (21); GB (6); KR (5)