Trial Title:
Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC
NCT ID:
NCT05814666
Condition:
HNSCC
Conditions: Official terms:
Squamous Cell Carcinoma of Head and Neck
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Danvatirsen
Description:
Danvatirsen is a STAT3 targeting drug.
Arm group label:
Danvatirsen plus pembrolizumab
Other name:
ISIS 481464
Other name:
AZD9150
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its
interaction with PD-L1 and PD-L2
Arm group label:
Danvatirsen plus pembrolizumab
Arm group label:
Pembrolizumab
Other name:
Keytruda
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.
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Arizona Cancer Center
Address:
City:
Tucson
Zip:
85719
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
520-621-2999
Facility:
Name:
University of California Irvine (UCI)
Address:
City:
Irvine
Zip:
92617
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Research Manager
Phone:
714-509-2643
Facility:
Name:
TMPN Hunt Cancer Care
Address:
City:
Torrance
Zip:
90505
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
310-750-3376
Facility:
Name:
University of California Los Angeles
Address:
City:
Westwood
Zip:
90024
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
310-794-2464
Facility:
Name:
University of Colorado Hospital (UCH) Anschutz Cancer Pavilion
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
303-724-9695
Facility:
Name:
Miami Cancer Institute
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
786-527-8546
Facility:
Name:
University of Illinois Cancer Center
Address:
City:
Chicago
Zip:
60612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Facility:
Name:
AMR Kansas City Oncology
Address:
City:
Merriam
Zip:
66204
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Manager
Phone:
913-386-7557
Facility:
Name:
University of Kansas Medical Center
Address:
City:
Westwood
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Project Manager
Phone:
913-574-2854
Facility:
Name:
Mary Bird Perkins Cancer Center
Address:
City:
Baton Rouge
Zip:
70809
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
225-215-1204
Facility:
Name:
Comprehensive Cancer Centers of Nevada
Address:
City:
Las Vegas
Zip:
89169
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Manager
Phone:
702-862-1100
Facility:
Name:
Morristown Medical Center
Address:
City:
Morristown
Zip:
07960
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Facility:
Name:
Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Manager
Phone:
212-824-7860
Facility:
Name:
Stony Brook Cancer Center
Address:
City:
Stony Brook
Zip:
11794
Country:
United States
Status:
Recruiting
Contact:
Last name:
Research Nurse
Phone:
631-216-2990
Facility:
Name:
The Christ Hospital Cancer Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Recruiting
Contact:
Last name:
Operations Manager
Phone:
513-585-1140
Facility:
Name:
University of Cincinnati Medical Center
Address:
City:
Cincinnati
Zip:
45229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
513-584-7703
Facility:
Name:
University Hospitals Cleveland
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
216-286-9469
Facility:
Name:
Prisma Health Cancer Institute
Address:
City:
Greenville
Zip:
29605
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Manager
Phone:
864-522-2066
Facility:
Name:
Dong-A University Hospital
Address:
City:
Busan
Zip:
49201
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator, 82-10-8843-0031
Facility:
Name:
Kosin University College of Medicine - Kosin University Gospel Hospital (KUGH)
Address:
City:
Busan
Zip:
602-702
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
82-51-990-5820
Facility:
Name:
Gyeongsang National University Hospital
Address:
City:
Jinju
Zip:
52727
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
82-10-2858-4757
Facility:
Name:
Korea University Medical Center (KUMC)
Address:
City:
Seoul
Zip:
02841
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
010-6227-6721
Facility:
Name:
Barts Health MHS Trust (Barts and The London NHS Trust) - St Bartholomew's (Barts) Hospital
Address:
City:
London
Zip:
EC1A 7BE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
44 02078828264
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
02031865258
Facility:
Name:
East and North Hertfordshire NHS Trust, Lister Hospital
Address:
City:
Northwood, Middlesex
Zip:
HA6 2RN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
0203 826 2153
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
Surry
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
02031865258
Start date:
May 30, 2023
Completion date:
May 30, 2026
Lead sponsor:
Agency:
Flamingo Therapeutics NV
Agency class:
Industry
Source:
Flamingo Therapeutics NV
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05814666
