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Trial record 1 of 1 for:    ASND0038
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TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (BelieveIT-201)

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ClinicalTrials.gov Identifier: NCT05980598
Recruitment Status : Recruiting
First Posted : August 8, 2023
Last Update Posted : April 25, 2024
Sponsor:
Information provided by (Responsible Party):
Ascendis Pharma A/S ( Ascendis Pharma Oncology Division A/S )

Study Description
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Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Head and Neck Neoplasms Drug: TransCon TLR7/8 Agonist Drug: Pembrolizumab Drug: TransCon IL-2 β/γ Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 29, 2023
Estimated Primary Completion Date : April 14, 2025
Estimated Study Completion Date : July 30, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Keytruda™


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Overall Survival [ Time Frame: Up to 5 years ]
    The time from randomization to death due to any cause.

  4. 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).


Eligibility Criteria
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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:

  • 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.
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): NCT05980598


Contacts
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Contact: Janet Connolly-Giva +1 (650) 512-2153 jcgt@ascendispharma.com

Locations
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United States, California
Ascendis Investigational Site Recruiting
Los Angeles, California, United States, 90067
United States, Michigan
Ascendis Investigational Site Recruiting
Detroit, Michigan, United States, 48201
United States, Ohio
Ascendis Pharma Investigational Site Recruiting
Canton, Ohio, United States, 44718
Ascendis Investigational Site Recruiting
Cincinnati, Ohio, United States, 45219
United States, Tennessee
Ascendis Investigational Site Recruiting
Knoxville, Tennessee, United States, 37902
Georgia
Ascendis Investigational Site Recruiting
Kutaisi, Imereti, Georgia, 4600
Ascendis Investigational Site Recruiting
Tbilisi, Georgia, 0114
Ascendis Investigational Site Recruiting
Tbilisi, Georgia, 0144
Ascendis Investigational Site II Recruiting
Tbilisi, Georgia, 0159
Ascendis Investigational Site Recruiting
Tbilisi, Georgia, 0159
Ascendis Investigational Site Recruiting
Tbilisi, Georgia, 0186
Germany
Ascendis Investigational Site Recruiting
Erlangen, Bavaria, Germany, 91054
Ascendis Investigational Site Recruiting
Mannheim, Germany, 68167
Hungary
Ascendis Investigational Site Recruiting
Pécs, Baranya, Hungary, 7624
Ascendis Investigational Site Recruiting
Debrecen, Hungary, 4032
Italy
Ascendis Investigational Site Recruiting
Meldola, FC, Italy, 47014
Spain
Ascendis Investigational Site Recruiting
Barcelona, Spain, 08003
Ascendis Investigational Site Recruiting
Madrid, Spain, 28027
Ascendis Investigational Site Recruiting
Madrid, Spain, 28040
Ascendis Investigational Site Recruiting
Málaga, Spain, 29011
Ascendis Investigational Site Recruiting
Pamplona, Spain, 31008
Ascendis Investigational Site Recruiting
Terrassa, Spain, 08221
Sponsors and Collaborators
Ascendis Pharma Oncology Division A/S
Investigators
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Study Director: Joan Morris Ascendis Pharma Oncology Division A/S
More Information
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Responsible Party: Ascendis Pharma Oncology Division A/S
ClinicalTrials.gov Identifier: NCT05980598    
Other Study ID Numbers: ASND0038
First Posted: August 8, 2023    Key Record Dates
Last Update Posted: April 25, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ascendis Pharma A/S ( Ascendis Pharma Oncology Division A/S ):
HNSCC
Head and Neck Cancer
TransCon TLR7/8 Agonist
TC TLR7/8
TransCon IL-2 β/γ
 TC IL-2 β/γ
Neoadjuvant
Neoadjuvant Head and Neck
LA-HNSCC
Locoregionally Advanced HNSCC
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
 Neoplasms, Squamous Cell
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action