TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (BelieveIT-201)

July 31, 2025 updated by: Ascendis Pharma A/S

BelieveIT-201: Phase 2, Randomized Open-labeled Trial of TransCon (TC) TLR7/8 Agonist in Combination With Pembrolizumab or With TC IL-2 β/γ, or Pembrolizumab Alone as Neoadjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

The purpose of this trial is to evaluate the safety and efficacy of TransCon TLR7/8 Agonist, TransCon IL-2 β/γ, and pembrolizumab given prior to curative intent surgery in treatment of participants with newly diagnosed Stage III/IVA resectable locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). After surgery, participants will receive local standard-of-care treatment and will be followed for safety, efficacy, and survival for up to 2 years.

This trial contains a safety run-in to evaluate the safety and tolerability of the two treatment arms: Arm A (TransCon TLR7/8 Agonist plus pembrolizumab) and Arm B (TransCon TLR7/8 Agonist plus TransCon IL-2 β/γ). The safety run-in will be followed by the randomized Phase 2, open-label part of the trial comparing the safety, efficacy and survival of treatment Arm A or Arm B compared to treatment Arm C (pembrolizumab monotherapy).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, Phase 2, open-label, multicenter trial of TransCon TLR7/8 Agonist in combination with pembrolizumab, TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ, or pembrolizumab monotherapy as neoadjuvant therapy in participants with Stage III-IVA resectable LA-HNSCC.

This trial starts with a safety run-in of 12 participants, 6 participants each in Arms A (TransCon TLR7/8 Agonist plus pembrolizumab) and B (TransCon TLR7/8 Agonist plus TransCon IL-2 β/γ) randomized 1:1.

After completing the safety run-in, 80 participants will be randomized in a 2:2:1 ratio in 3 treatment Arms A, B or C (pembrolizumab monotherapy).

Once randomized, participants should begin treatment within 5 calendar days. Participants enrolled after the safety run-in, into the 2:2:1 randomization part of the trial, will be stratified as follows: oropharyngeal HPV p16 positive versus oropharyngeal HPV p16 negative or larynx/hypopharyngeal/oral cavity regardless of HPV p16 status. All participants should receive study drug(s) every 21 days (Q21D) for 2 cycles followed by curative-intent surgery. After surgery, participants may receive standard-of-care treatment in the adjuvant setting, as per investigator's decision and local guidelines.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Georgia
      • Tbilisi, Georgia, 0114
        • Ascendis Investigational Site
      • Tbilisi, Georgia, 0144
        • Ascendis Investigational Site
      • Tbilisi, Georgia, 0159
        • Ascendis Investigational Site II
      • Tbilisi, Georgia, 0159
        • Ascendis Investigational Site
      • Tbilisi, Georgia, 0186
        • Ascendis Investigational Site
    • Imereti
      • Kutaisi, Imereti, Georgia, 4600
        • Ascendis Investigational Site
  • Germany
      • Greifswald, Germany, 17475
        • Ascendis Investigational Site
      • Jena, Germany, 07747
        • Ascendis Investigational Site
      • Leipzig, Germany, 04103
        • Ascendis Investigational Site
      • Mannheim, Germany, 68167
        • Ascendis Investigational Site
      • Ulm, Germany, 89075
        • Ascendis Investigational Site
    • Bavaria
      • Erlangen, Bavaria, Germany, 91054
        • Ascendis Investigational Site
  • Hungary
      • Budapest, Hungary, 1122
        • Ascendis Investigational Site
      • Debrecen, Hungary, 4032
        • Ascendis Investigational Site
      • Győr, Hungary, 9024
        • Ascendis Investigational Site
      • Zalaegerszeg, Hungary, 8900
        • Ascendis Investigational Site
    • Baranya
      • Pécs, Baranya, Hungary, 7624
        • Ascendis Investigational Site
  • Italy
      • Meldola, Italy, 47014
        • Ascendis Investigational Site
      • Milan, Italy, 20133
        • Ascendis Investigational Site
      • Milan, Italy, 20141
        • Ascendis Investigational Site
      • Modena, Italy, 41125
        • Ascendis Investigational Site
      • Naples, Italy, 80131
        • Ascendis Investigational Site
      • Novara, Italy, 28100
        • Ascendis Investigational Site
      • Pavia, Italy, 27100
        • Ascendis Investigational Site
      • Rozzano, Italy, 20089
        • Ascendis Investigational Site
  • Poland
      • Gliwice, Poland, 44-102
        • Ascendis Investigational Site
      • Siedlce, Poland, 08-110
        • Ascendis Investigational Site
      • Warszawa, Poland, 02-781
        • Ascendis Investigational Site
  • Spain
      • Barcelona, Spain, 08003
        • Ascendis Investigational Site
      • Barcelona, Spain, 08035
        • Ascendis Investigational Site
      • El Palmar, Spain, 30120
        • Ascendis Investigational Site
      • L'Hospitalet De Llobregat, Spain, 08908
        • Ascendis Investigational Site
      • Lugo, Spain, 27003
        • Ascendis Investigational Site
      • Madrid, Spain, 28027
        • Ascendis Investigational Site
      • Madrid, Spain, 28040
        • Ascendis Investigational Site
      • Madrid, Spain, 28050
        • Ascendis Investigational Site
      • Madrid, Spain, 28040
        • Ascendis Investigational Site II
      • Málaga, Spain, 29011
        • Ascendis Investigational Site
      • Pamplona, Spain, 31008
        • Ascendis Investigational Site
      • Terrassa, Spain, 08221
        • Ascendis Investigational Site
      • Valencia, Spain, 46009
        • Ascendis Investigational Site
      • Valencia, Spain, 46014
        • Ascendis Investigational Site
      • Valencia, Spain, 46026
        • Ascendis Investigational Site
      • Zaragoza, Spain, 50009
        • Ascendis Investigational Site
  • Taiwan
      • Kaohsiung City, Taiwan, 80708
        • Ascendis Investigational Site
      • Kaohsiung City, Taiwan, 83301
        • Ascendis Investigational Site
      • Taichung, Taiwan, 404
        • Ascendis Investigational Site
      • Tainan, Taiwan, 70456
        • Ascendis Investigational Site
      • Taoyuan, Taiwan, 333
        • Ascendis Investigational Site
  • United States
    • California
      • Los Angeles, California, United States, 90067
        • Ascendis Investigational Site
      • San Francisco, California, United States, 94158
        • Ascendis Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Ascendis Investigational Site
      • Springfield, Illinois, United States, 62702
        • Ascendis Investigational Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Ascendis Investigational Site
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Ascendis Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Ascendis Investigational Site
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Ascendis Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Ascendis Investigational Site
    • New York
      • New York, New York, United States, 11794
        • Ascendis Investigational Site
    • Ohio
      • Canton, Ohio, United States, 44718
        • Ascendis Pharma Investigational Site
      • Cincinnati, Ohio, United States, 45219
        • Ascendis Investigational Site
      • Columbus, Ohio, United States, 43210
        • Ascendis Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Ascendis Investigational Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37902
        • Ascendis Investigational Site
    • Texas
      • Houston, Texas, United States, 77030
        • Ascendis Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has local histologically confirmed new diagnosis of resectable, non-metastatic, SCC that is either: Stage III tumor HPV-positive oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no distant metastases (M) 0; Stage III or IVA oropharyngeal tumor HPV-negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries regardless of HPV status (per American Joint Committee on Cancer [AJCC] Staging, 8th edition).
  • Has available archived or fresh core or excisional biopsy of a tumor lesion. Note: Fine needle aspirations may be allowed after discussion with Medical Monitor.
  • Is eligible and plans for primary LA-HNSCC surgery based on investigator decision and per local practice.
  • Has results from tumor HPV status by p16 immunohistochemistry (IHC) for oropharyngeal tumors. (HPV DNA analysis for HPV tumor status is acceptable if that is the local standard of care analysis.)
  • Has adequate organ function at screening.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Has at least one lesion that is deemed by the investigator to be easily and safely accessible for IT injection.

Exclusion Criteria:

  • Active autoimmune conditions.
  • Has significant cardiac disease.
  • Has a known bleeding disorder that is deemed to place the participant at unacceptable risk for bleeding complications from IT injections or biopsies.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TransCon TLR7/8 Agonist in combination with pembrolizumab
Participants receive 2 cycles, once every 3 weeks of TransCon TLR7/8 Agonist intratumoral (IT) injection in combination with pembrolizumab as a 30-minute intravenous (IV) infusion
Drug: TransCon TLR7/8 Agonist
TLR7/8 agonist prodrug
Drug: Pembrolizumab
A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer cells from hiding
Other Names:
  • Keytruda™
Experimental: TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
Participants receive 2 cycles, once every 3 weeks of TransCon TLR7/8 Agonist (IT injection) in combination with TransCon IL-2 β/γ as a 30-minute IV infusion
Drug: TransCon TLR7/8 Agonist
TLR7/8 agonist prodrug
Drug: TransCon IL-2 β/γ
Sustained systemic release of IL-2 β/γ with selective receptor binding that may stimulate the immune system to kill cancer cells
Active Comparator: Pembrolizumab
Participants receive 2 cycles, once every 3 weeks of pembrolizumab alone as a 30-minute IV infusion
Drug: Pembrolizumab
A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer cells from hiding
Other Names:
  • Keytruda™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathological Response
Time Frame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
The proportion of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.
Up to 6 weeks after Cycle 2 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response
Time Frame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
A central pathology laboratory and local hospital pathologist will evaluate if all the tumor is completely gone from the primary tumor and all the lymph nodes that were removed at surgery.
Up to 6 weeks after Cycle 2 (each cycle is 21 days)
Event Free Survival
Time Frame: Up to 5 years
The time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence determined by radiology scans or tumor biopsy as needed, or death due to any cause.
Up to 5 years
Overall Survival
Time Frame: Up to 5 years
The time from randomization to death due to any cause.
Up to 5 years
Safety and Tolerability
Time Frame: From time of signing of the ICF up to 100 (±7) days following the last dose of study drug
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
From time of signing of the ICF up to 100 (±7) days following the last dose of study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ascendis Pharma A/S

Investigators

  • Study Director: Joan Morris, Ascendis Pharma Oncology Division A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2023

Primary Completion (Actual)

March 28, 2025

Study Completion (Actual)

March 28, 2025

Study Registration Dates

First Submitted

July 20, 2023

First Submitted That Met QC Criteria

August 4, 2023

First Posted (Actual)

August 8, 2023

Study Record Updates

Last Update Posted (Actual)

August 1, 2025

Last Update Submitted That Met QC Criteria

July 31, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASND0038

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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