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Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (PEMDA-HN)

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ClinicalTrials.gov Identifier: NCT05814666
Recruitment Status : Recruiting
First Posted : April 18, 2023
Last Update Posted : April 10, 2024
Sponsor:
Information provided by (Responsible Party):
Flamingo Therapeutics NV

Study Description
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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 Intervention/treatment Phase
HNSCC Drug: Danvatirsen Drug: Pembrolizumab Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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 : May 30, 2023
Estimated Primary Completion Date : May 30, 2025
Estimated Study Completion Date : May 30, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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 Name: 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 Name: Keytruda


Outcome Measures
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Primary Outcome Measures :
  1. Confirmed ORR [ Time Frame: Up to 18 months ]
    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


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 18 months ]
    Drug induced toxicities are assessed and graded according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0.

  2. DOR [ Time Frame: Up to 18months ]
    Duration of Response by RECIST v1.1

  3. DCR & CR Rate [ Time Frame: Up to 18months ]
    Disease control rate and complete response rate by RECIST v1.1

  4. ORR in tumors with CPS ≥50 [ Time Frame: Up to 18months ]
    Overall response rate per RECIST v1.1 in tumors with CPS ≥ 20 and ≥ 50

  5. DOR in tumors with CPS ≥50 [ Time Frame: Up to 18months ]
    Duration of response by RECIST v1.1 in tumors with CPS ≥50

  6. PFS [ Time Frame: Up to 18months ]
    Progression-free survival by RECIST v1.1, defined as the time from randomization to the first documentation of progressive disease (PD) or death from any cause, whichever comes first

  7. OS [ Time Frame: Up to 30months ]
    Overall survival, defined as time from randomization to death from any cause

  8. Maximum plasma concentration [ Time Frame: Up to 18 months ]
    Maximum concentration recorded [Cmax]of danvatirsen at defined timepoints in the combination regimen

  9. Trough concentration [ Time Frame: Up to 18 months ]
    Trough concentration [Ctrough] of danvatirsen at defined timepoints in the combination regimen

  10. Area under the plasma concentration-time curve [ Time Frame: Up to 18 months ]
    Area under the plasma concentration-time curve over the dosing interval [AUCtau] of danvatirsen at defined timepoints in the combination regimen

  11. Time to maximum plasma concentration [ Time Frame: Up to 18 months ]
    Time to maximum plasma concentration [Tmax]) after single and multiple doses at defined timepoints in the combination regimen

  12. Immunogenicity of danvatirsen [ Time Frame: Up to 18 months ]
    Anti-danvatirsen antibody titers at defined timepoints in the combination regimen


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05814666


Contacts
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Contact: Flamingo Therapeutics +1 484 482 0007 clinical@flamingotx.com

Locations
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United States, Arizona
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85719
Contact: Study Coordinator         
Contact    520-621-2999      
United States, California
University of California Irvine (UCI) Recruiting
Irvine, California, United States, 92617
Contact: Clinical Research Manager    714-509-2643      
TMPN Hunt Cancer Care Recruiting
Torrance, California, United States, 90505
Contact: Study Coordinator    310-750-3376      
University of California Los Angeles Recruiting
Westwood, California, United States, 90024
Contact: Study Coordinator    310-794-2464      
United States, Colorado
University of Colorado Hospital (UCH) Anschutz Cancer Pavilion Recruiting
Aurora, Colorado, United States, 80045
Contact: Study Coordinator         
United States, Florida
Miami Cancer Institute Recruiting
Miami, Florida, United States, 33176
Contact: Study Coordinator         
Contact    786-527-8546      
United States, Kansas
AMR Kansas City Oncology Recruiting
Merriam, Kansas, United States, 66204
Contact: Site Manager    913-386-7557      
University of Kansas Medical Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Project Manager    913-574-2854      
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Site Manager    702-862-1100      
United States, New York
Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Clinical Trials Manager    212-824-7860      
Stony Brook Cancer Center Recruiting
Stony Brook, New York, United States, 11794
Contact: Research Nurse         
Contact    631-216-2990      
United States, Ohio
The Christ Hospital Cancer Center Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Operations Manager    513-585-1140      
University of Cincinnati Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Study Coordinator         
Contact    513-584-7703      
University Hospitals Cleveland Recruiting
Cleveland, Ohio, United States, 44106
Contact: Study Coordinator         
Contact    216-286-9469      
United States, South Carolina
Prisma Health Cancer Institute Recruiting
Greenville, South Carolina, United States, 29605
Contact: Site Manager    864-522-2066      
Korea, Republic of
Gyeongsang National University Hospital Recruiting
Jinju, Korea, Republic of, 52727
Contact: Study Coordinator         
Contact    82-10-2858-4757      
Sponsors and Collaborators
Flamingo Therapeutics NV
More Information
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Responsible Party: Flamingo Therapeutics NV
ClinicalTrials.gov Identifier: NCT05814666    
Other Study ID Numbers: FLM-6774-201
First Posted: April 18, 2023    Key Record Dates
Last Update Posted: April 10, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Head and Neck Neoplasms
 Neoplasms by Site
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action