A Phase 2 interventional study of TransCon TLR7/8 Agonist and Pembrolizumab in Head and Neck Neoplasms, sponsored by Ascendis Pharma A/S. Terminated at 65 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-01.
Sponsored by Ascendis Pharma A/S · Phase 2, Interventional, and Treatment
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).
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.
2,344 studies on the registry are indexed under Head and Neck Neoplasms; 551 are open to participants now.
This study's enrollment of 27 is below the median of 47 across 1,751 interventional studies indexed under Head and Neck Neoplasms.
Browse Head and Neck Neoplasms studies →Ascendis Pharma A/S is the lead sponsor of 15 studies on the registry; 6 are open to participants now.
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Exclusion Criteria:
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
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
Participants receive 2 cycles, once every 3 weeks of pembrolizumab alone as a 30-minute IV infusion
Drug: Pembrolizumab
TLR7/8 agonist prodrug
A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer cells from hiding
Also known as: Keytruda™
Sustained systemic release of IL-2 β/γ with selective receptor binding that may stimulate the immune system to kill cancer cells
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.
Time frame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
Pathological Complete Response
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.
Time frame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
Event Free Survival
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.
Time frame: Up to 5 years
Overall Survival
The time from randomization to death due to any cause.
Time frame: Up to 5 years
Safety and Tolerability
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Time frame: From time of signing of the ICF up to 100 (±7) days following the last dose of study drug
Plan to share: No
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This study is terminated, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.
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Ascendis Pharma A/S