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

Ascendis Pharma

Status and phase: Terminated; Phase 2

Conditions: Head and Neck Neoplasms

Treatments: Drug: TransCon IL-2 β/γ; Drug: TransCon TLR7/8 Agonist; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05980598

ASND0038

Details and patient eligibility

About

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).

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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27 participants in 3 patient groups

TransCon TLR7/8 Agonist in combination with pembrolizumab

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab

Drug: TransCon TLR7/8 Agonist

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

Experimental group

Description:

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

Treatment:

Drug: TransCon IL-2 β/γ

Drug: TransCon TLR7/8 Agonist

Pembrolizumab

Active Comparator group

Description:

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

Treatment:

Drug: Pembrolizumab