Clinical trial NCT05980598: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Ascendis Pharma A/S
Sponsor class: INDUSTRY
First posted: 2023-08-08
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Major Pathological Response
timeFrame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
Secondary outcomes:
measure: Pathological Complete Response
timeFrame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
measure: Event Free Survival
timeFrame: Up to 5 years
measure: Overall Survival
timeFrame: Up to 5 years
measure: Safety and Tolerability
timeFrame: From time of signing of the ICF up to 100 (±7) days following the last dose of study drug
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ascendis Investigational Site
state: California
city: San Francisco
country: United States
facility: Ascendis Investigational Site
state: California
city: Chicago
country: United States
facility: Ascendis Investigational Site
state: Illinois
city: Springfield
country: United States
facility: Ascendis Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: Ascendis Investigational Site
state: Iowa
city: Louisville
country: United States
facility: Ascendis Investigational Site
state: Kentucky
city: Boston
country: United States
facility: Ascendis Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Ascendis Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Ascendis Investigational Site
state: Minnesota
city: New York
country: United States
facility: Ascendis Investigational Site
state: New York
city: Canton
country: United States
facility: Ascendis Pharma Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Ascendis Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Ascendis Investigational Site
state: Ohio
city: Charleston
country: United States
facility: Ascendis Investigational Site
state: South Carolina
city: Knoxville
country: United States
facility: Ascendis Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Ascendis Investigational Site
state: Texas
city: Kutaisi
country: Georgia
facility: Ascendis Investigational Site
state: Imereti
city: Tbilisi
country: Georgia
facility: Ascendis Investigational Site
city: Tbilisi
country: Georgia
facility: Ascendis Investigational Site
city: Tbilisi
country: Georgia
facility: Ascendis Investigational Site II
city: Tbilisi
country: Georgia
facility: Ascendis Investigational Site
city: Tbilisi
country: Georgia
facility: Ascendis Investigational Site
city: Erlangen
country: Germany
facility: Ascendis Investigational Site
state: Bavaria
city: Greifswald
country: Germany
facility: Ascendis Investigational Site
city: Jena
country: Germany
facility: Ascendis Investigational Site
city: Leipzig
country: Germany
facility: Ascendis Investigational Site
city: Mannheim
country: Germany
facility: Ascendis Investigational Site
city: Ulm
country: Germany
facility: Ascendis Investigational Site
city: Pécs
country: Hungary
facility: Ascendis Investigational Site
state: Baranya
city: Budapest
country: Hungary
facility: Ascendis Investigational Site
city: Debrecen
country: Hungary
facility: Ascendis Investigational Site
city: Győr
country: Hungary
facility: Ascendis Investigational Site
city: Zalaegerszeg
country: Hungary
facility: Ascendis Investigational Site
city: Meldola
country: Italy
facility: Ascendis Investigational Site
city: Milan
country: Italy
facility: Ascendis Investigational Site
city: Milan
country: Italy
facility: Ascendis Investigational Site
city: Modena
country: Italy
facility: Ascendis Investigational Site
city: Naples
country: Italy
facility: Ascendis Investigational Site
city: Novara
country: Italy
facility: Ascendis Investigational Site
city: Pavia
country: Italy
facility: Ascendis Investigational Site
city: Rozzano
country: Italy
facility: Ascendis Investigational Site
city: Gliwice
country: Poland
facility: Ascendis Investigational Site
city: Siedlce
country: Poland
facility: Ascendis Investigational Site
city: Warszawa
country: Poland
facility: Ascendis Investigational Site
city: Barcelona
country: Spain
facility: Ascendis Investigational Site
city: Barcelona
country: Spain
facility: Ascendis Investigational Site
city: El Palmar
country: Spain
facility: Ascendis Investigational Site
city: L'Hospitalet De Llobregat
country: Spain
facility: Ascendis Investigational Site
city: Lugo
country: Spain
facility: Ascendis Investigational Site
city: Madrid
country: Spain
facility: Ascendis Investigational Site
city: Madrid
country: Spain
facility: Ascendis Investigational Site II
city: Madrid
country: Spain
facility: Ascendis Investigational Site
city: Madrid
country: Spain
facility: Ascendis Investigational Site
city: Málaga
country: Spain
facility: Ascendis Investigational Site
city: Pamplona
country: Spain
facility: Ascendis Investigational Site
city: Terrassa
country: Spain
facility: Ascendis Investigational Site
city: Valencia
country: Spain
facility: Ascendis Investigational Site
city: Valencia
country: Spain
facility: Ascendis Investigational Site
city: Valencia
country: Spain
facility: Ascendis Investigational Site
city: Zaragoza
country: Spain
facility: Ascendis Investigational Site
city: Kaohsiung City
country: Taiwan
facility: Ascendis Investigational Site
city: Kaohsiung City
country: Taiwan
facility: Ascendis Investigational Site
city: Taichung
country: Taiwan
facility: Ascendis Investigational Site
city: Tainan
country: Taiwan
facility: Ascendis Investigational Site
city: Taoyuan
country: Taiwan
facility: Ascendis Investigational Site
Study officials:
affiliation: Ascendis Pharma Oncology Division A/S
name: Joan Morris
role: STUDY_DIRECTOR
References: