HNSCCPhase 2PEMDA-HNNCT05814666
Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC
A Phase 2 study testing Danvatirsen and Pembrolizumab in people with HNSCC, run by Flamingo Therapeutics NV at 32 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HNSCC
- What is being tested?
- Danvatirsen and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 32 sitesin 3 countries
- Study dates
- 30 May 2023to 14 Aug 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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.
- Treated or untreated parenchymal brain metastases or leptomeningeal disease.
- 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.
- Hypersensitivity to any component of danvatirsen or pembrolizumab.
Trial locations and contacts
32 sites in 3 countries.
32 sites in 3 countries
United States21 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
University of Colorado Hospital (UCH) Anschutz Cancer Pavilion
Aurora, Colorado, 80045
University of Maryland Baltimore, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
University of Illinois Cancer Center
Chicago, Illinois, 60612
The Christ Hospital Cancer Center
Cincinnati, Ohio, 45219
University of Cincinnati Medical Center
Cincinnati, Ohio, 45229
University Hospitals Cleveland
Cleveland, Ohio, 44106
UT Southwestern Medical Center/Simmons Comprehensive Cancer Center
Dallas, Texas, 75390
Prisma Health Cancer Institute
Greenville, South Carolina, 29605
University of California Irvine (UCI)
Irvine, California, 92617
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
AMR Kansas City Oncology
Merriam, Kansas, 66204
Miami Cancer Institute
Miami, Florida, 33176
Morristown Medical Center
Morristown, New Jersey, 07960
Mount Sinai
New York, New York, 10029
Stony Brook Cancer Center
Stony Brook, New York, 11794
TMPN Hunt Cancer Care
Torrance, California, 90505
The University of Arizona Cancer Center
Tucson, Arizona, 85719
University of Kansas Medical Center
Westwood, Kansas, 66205
University of California Los Angeles
Westwood, Los Angeles, California, 90024
United Kingdom6 sites
Saint James's University Hospital (SJUH) - St James's Institute of Oncology
Leeds
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool
Barts Health MHS Trust (Barts and The London NHS Trust) - St Bartholomew's (Barts) Hospital
London, EC1A 7BE
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
East and North Hertfordshire NHS Trust, Lister Hospital
Northwood, HA6 2RN
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
South Korea5 sites
Dong-A University Hospital
Busan, 49201
Kosin University College of Medicine - Kosin University Gospel Hospital (KUGH)
Busan, 602-702
Gyeongsang National University Hospital
Jinju, 52727
Korea University Medical Center (KUMC)
Seoul, 02841
The Catholic University of Korea - Eunpyeong St. Mary's Hospital
Seoul
About this study
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)
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.
Read the 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.
- Conditions
- HNSCC
- Being tested
- Danvatirsen, Pembrolizumab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DanvatirsenDrug
Also called ISIS 481464, AZD9150
Danvatirsen is a STAT3 targeting drug.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Danvatirsen; Drug: Pembrolizumab |
| Pembrolizumab | Active comparator | Pembrolizumab IV every 3 weeks Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 18 months
Secondary outcomes (12)
Number of Participants With Adverse Events as Assessed by CTCAE v5.0
Adverse Events are assessed and graded according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0.
Measured: Up to 18 months
DOR
Duration of Response by RECIST v1.1
Measured: Up to 18months
DCR & CR Rate
Disease control rate and complete response rate by RECIST v1.1
Measured: Up to 18months
ORR in Tumors With CPS ≥20 and ≥ 50
Overall response rate per RECIST v1.1 in tumors with CPS< 20, CPS ≥ 20 and CPS ≥ 50
Measured: Up to 18months
DOR in Tumors With CPS ≥20 and ≥50
Duration of response by RECIST v1.1 in tumors with CPS ≥ 20 and ≥50
Measured: Up to 18months
PFS
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
Measured: Up to 18months
OS
Overall survival, defined as time from randomization to death from any cause
Measured: Up to 30months
Maximum Plasma Concentration
Maximum concentration recorded [Cmax]of danvatirsen at defined timepoints in the combination regimen
Measured: Up to 18 months
Trough Concentration
Trough concentration [Ctrough] of danvatirsen at defined timepoints in the combination regimen
Measured: Up to 18 months
Area Under the Plasma Concentration-time Curve
Area under the plasma concentration-time curve over the dosing interval [AUCtau] of danvatirsen at defined timepoints in the combination regimen
Measured: Up to 18 months
Time to Maximum Plasma Concentration
Time to maximum plasma concentration [Tmax]) after single and multiple doses at defined timepoints in the combination regimen
Measured: Up to 18 months
Immunogenicity of Danvatirsen
Anti-danvatirsen antibody titers at defined timepoints in the combination regimen
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start30 May 2023
- Primary completion14 Aug 2025
- Study completion14 Aug 2025
Why it stopped: Interim analysis was negative
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HNSCCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Flamingo Therapeutics NV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nabil Saba, MD, Study chair, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05814666
- Sponsor's protocol ID
- FLM-6774-201
- Acronym
- PEMDA-HN
- Status last verified
- Dec 2025
- First submitted
- 10 Mar 2023
- Last updated
- 30 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05814666
- Acronym / sponsor ID
- PEMDA-HN / FLM-6774-201
- Conditions
- HNSCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis was negative
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Flamingo Therapeutics NVIndustry (pharma, biotech, devices)
- Study start
- 30 May 2023 (actual)
- Primary completion
- 14 Aug 2025 (actual)
- Study completion
- 14 Aug 2025 (actual)
- First posted
- 18 Apr 2023 (actual)
- Results
- Posted 30 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Danvatirsen plus pembrolizumab | Experimental | Drug: Danvatirsen, Drug: PembrolizumabDanvatirsen 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. |
| Pembrolizumab | Active comparator | Drug: PembrolizumabPembrolizumab IV every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DanvatirsenAlso: ISIS 481464, AZD9150Danvatirsen is a STAT3 targeting drug. | Drug | Danvatirsen plus pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2 | Drug | Danvatirsen plus pembrolizumab, Pembrolizumab |
Primary outcome
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
12 secondary outcomes
Number of Participants With Adverse Events as Assessed by CTCAE v5.0
Time frame: Up to 18 months
DOR
Time frame: Up to 18months
DCR & CR Rate
Time frame: Up to 18months
ORR in Tumors With CPS ≥20 and ≥ 50
Time frame: Up to 18months
DOR in Tumors With CPS ≥20 and ≥50
Time frame: Up to 18months
PFS
Time frame: Up to 18months
OS
Time frame: Up to 30months
Maximum Plasma Concentration
Time frame: Up to 18 months
Trough Concentration
Time frame: Up to 18 months
Area Under the Plasma Concentration-time Curve
Time frame: Up to 18 months
Time to Maximum Plasma Concentration
Time frame: Up to 18 months
Immunogenicity of Danvatirsen
Time frame: Up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for HNSCC
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nabil Saba, MD study chair
Emory University
32 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Danvatirsen and Pembrolizumab in people with HNSCC, run by Flamingo Therapeutics NV at 32 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, United Kingdom, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed ORR (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2026.