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

NCT05980598 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: ASND0038
• Study Type: interventional
• Target: 27
• Locations: 8 countries
• Sites: 65

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).

Conditions

Head and Neck Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response

  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 Outcomes (4)

• Pathological Complete Response

  Up to 6 weeks after Cycle 2 (each cycle is 21 days)

• Event Free Survival

  Up to 5 years

• Overall Survival

  Up to 5 years

• Safety and Tolerability

  From time of signing of the ICF up to 100 (±7) days following the last dose of study drug

Study Arms (3)

TransCon TLR7/8 Agonist in combination with pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ

EXPERIMENTAL

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; Drug: TransCon IL-2 β/γ

Pembrolizumab

ACTIVE COMPARATOR

Participants receive 2 cycles, once every 3 weeks of pembrolizumab alone as a 30-minute IV infusion

Drug: Pembrolizumab

Interventions

TransCon TLR7/8 Agonist DRUG

TLR7/8 agonist prodrug

TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ; TransCon TLR7/8 Agonist in combination with pembrolizumab

Pembrolizumab DRUG

A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer cells from hiding

Also known as: Keytruda™

Pembrolizumab; TransCon TLR7/8 Agonist in combination with pembrolizumab

TransCon IL-2 β/γ DRUG

Sustained systemic release of IL-2 β/γ with selective receptor binding that may stimulate the immune system to kill cancer cells

TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ascendis Pharma A/S: lead

Study Sites (65)

Ascendis Investigational Site

Los Angeles, California, 90067, United States

Location

Ascendis Investigational Site

San Francisco, California, 94158, United States

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Ascendis Investigational Site

Chicago, Illinois, 60612, United States

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Ascendis Investigational Site

Springfield, Illinois, 62702, United States

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Ascendis Investigational Site

Iowa City, Iowa, 52242, United States

Location

Ascendis Investigational Site

Louisville, Kentucky, 40202, United States

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Ascendis Investigational Site

Boston, Massachusetts, 02114, United States

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Ascendis Investigational Site

Detroit, Michigan, 48201, United States

Location

Ascendis Investigational Site

Rochester, Minnesota, 55905, United States

Location

Ascendis Investigational Site

New York, New York, 11794, United States

Location

Ascendis Pharma Investigational Site

Canton, Ohio, 44718, United States

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Ascendis Investigational Site

Cincinnati, Ohio, 45219, United States

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Ascendis Investigational Site

Columbus, Ohio, 43210, United States

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Ascendis Investigational Site

Charleston, South Carolina, 29425, United States

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Ascendis Investigational Site

Knoxville, Tennessee, 37902, United States

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Ascendis Investigational Site

Houston, Texas, 77030, United States

Location

Ascendis Investigational Site

Kutaisi, Imereti, 4600, Georgia

Location

Ascendis Investigational Site

Tbilisi, 0114, Georgia

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Ascendis Investigational Site

Tbilisi, 0144, Georgia

Location

Ascendis Investigational Site II

Tbilisi, 0159, Georgia

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Ascendis Investigational Site

Tbilisi, 0159, Georgia

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Ascendis Investigational Site

Tbilisi, 0186, Georgia

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Ascendis Investigational Site

Erlangen, Bavaria, 91054, Germany

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Ascendis Investigational Site

Greifswald, 17475, Germany

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Ascendis Investigational Site

Jena, 07747, Germany

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Ascendis Investigational Site

Leipzig, 04103, Germany

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Ascendis Investigational Site

Mannheim, 68167, Germany

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Ascendis Investigational Site

Ulm, 89075, Germany

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Ascendis Investigational Site

Pécs, Baranya, 7624, Hungary

Location

Ascendis Investigational Site

Budapest, 1122, Hungary

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Ascendis Investigational Site

Debrecen, 4032, Hungary

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Ascendis Investigational Site

Győr, 9024, Hungary

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Ascendis Investigational Site

Zalaegerszeg, 8900, Hungary

Location

Ascendis Investigational Site

Meldola, 47014, Italy

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Ascendis Investigational Site

Milan, 20133, Italy

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Ascendis Investigational Site

Milan, 20141, Italy

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Ascendis Investigational Site

Modena, 41125, Italy

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Ascendis Investigational Site

Naples, 80131, Italy

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Ascendis Investigational Site

Novara, 28100, Italy

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Ascendis Investigational Site

Pavia, 27100, Italy

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Ascendis Investigational Site

Rozzano, 20089, Italy

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Ascendis Investigational Site

Gliwice, 44-102, Poland

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Ascendis Investigational Site

Siedlce, 08-110, Poland

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Ascendis Investigational Site

Warsaw, 02-781, Poland

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Ascendis Investigational Site

Barcelona, 08003, Spain

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Ascendis Investigational Site

Barcelona, 08035, Spain

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Ascendis Investigational Site

El Palmar, 30120, Spain

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Ascendis Investigational Site

L'Hospitalet de Llobregat, 08908, Spain

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Ascendis Investigational Site

Lugo, 27003, Spain

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Ascendis Investigational Site

Madrid, 28027, Spain

Location

Ascendis Investigational Site II

Madrid, 28040, Spain

Location

Ascendis Investigational Site

Madrid, 28040, Spain

Location

Ascendis Investigational Site

Madrid, 28050, Spain

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Ascendis Investigational Site

Málaga, 29011, Spain

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Ascendis Investigational Site

Pamplona, 31008, Spain

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Ascendis Investigational Site

Terrassa, 08221, Spain

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Ascendis Investigational Site

Valencia, 46009, Spain

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Ascendis Investigational Site

Valencia, 46014, Spain

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Ascendis Investigational Site

Valencia, 46026, Spain

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Ascendis Investigational Site

Zaragoza, 50009, Spain

Location

Ascendis Investigational Site

Kaohsiung City, 80708, Taiwan

Location

Ascendis Investigational Site

Kaohsiung City, 83301, Taiwan

Location

Ascendis Investigational Site

Taichung, 404, Taiwan

Location

Ascendis Investigational Site

Tainan, 70456, Taiwan

Location

Ascendis Investigational Site

Taoyuan District, 333, Taiwan

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Joan Morris

  Ascendis Pharma Oncology Division A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2023
• First Posted: August 8, 2023
• Study Start: September 29, 2023
• Primary Completion: March 28, 2025
• Study Completion: March 28, 2025
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8); DE (6); HU (5); TW (5); US (16); GE (6); ES (16); PL (3)