A Trial to Investigate 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 Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC)

Trial details

Who runs it

Ascendis Pharma Oncology Division A/S

Trial code

EU 2023-506092-10-00

Record updated

2025. május 7.

Original description

To evaluate MPR of TransCon TLR7/8 Agonist in combination with pembrolizumab and TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ as compared with pembrolizumab monotherapyRead full original descriptionShow less

BelieveIT-201: A Randomized, Phase 2, Open-label 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 Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC)

To evaluate MPR of TransCon TLR7/8 Agonist in combination with pembrolizumab and TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ as compared with pembrolizumab monotherapy

Inclusion: Participants must be at least 18 years of age at the time of signing the informed consent; Has at least one lesion that is deemed by the investigator to be easily and safely accessible for IT injection; For women of childbearing potential (WOCBP): agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods (those with a failure rate of <1% per year), and agreement to refrain from donating eggs, from the time of a negative pregnancy test at screening, during the treatment period, and for 160 days after the last dose of study drug, or per local guidelines, whichever is longer; For men with a female partner of childbearing potential or pregnant female partner: agreement to remain abstinent (refrain from heterosexual intercourse) or use a double barrier method of contraception (i.e., condom plus spermicide), and agreement to refrain from donating sperm during the treatment period (C1D1) and for 160 days following the last dose of study drug or per local guidelines, whichever is longer: For male participants with a female partner, see the paragraph in inclusion criterion 11 regarding the reliability of sexual abstinence; Capable of giving signed informed consent as described in Appendix 3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; 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 (M0); Stage III or IVA oropharyngeal tumor HPV-negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries regardless of HPV status (as per American Joint Committee on Cancer [AJCC] Staging, 8th edition, see Appendix 13 of the protocol; 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 testing tumor HPV status by p16 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: 7.1 Total bilirubin ≤1.5 × upper limit of normal (ULN) (<3 × ULN if participant has history of Gilbert’s Syndrome). 7.2 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3 × ULN. 7.3 Creatinine clearance (CrCl) ≥45 mL/min (calculated by the Cockcroft-Gault Equation, see Appendix 9 of the protocol). 7.4 Absolute neutrophil count (ANC) ≥1.0 × 10^9/L (1000/mm^3). 7.5 Hemoglobin ≥9 g/dL. 7.6 Platelet count ≥75 × 10^9/L (75,000/mm^3). 7.7 International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless participant is receiving anticoagulant therapy. 7.8 Thyroid-stimulating hormone (TSH) within normal limits. If TSH is not within normal limits, participant will be considered eligible if total T3 or free T4 are within normal limits; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; In the opinion of the investigator, participant is able to adhere to the treatment schedule and required assessments so as not to incur a delay of the definitive surgery.

Exclusion: Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization; Vaccination with live, attenuated vaccines within 4 weeks of C1D1; Prior treatment with or known hypersensitivity or allergy(ies) to any systemic anticancer treatment (approved or investigational) to include IL-2, IL-2 variants, TLR agonists, anti-PD-1, anti-PD-L1, and variants; Has received prior radiotherapy or systemic anticancer therapy for HNSCC; Active autoimmune conditions, regardless of need for immunosuppressive treatment at the time of screening, with the exception of participants well controlled on physiologic endocrine replacement; Cardiopatía significativa definida por: 2.1 Insuficiencia cardíaca congestiva de clase III o IV según la Asociación Neoyorquina de Cardiología o la Sociedad Europea de Cardiología. 2.2 Angina inestable. 2.3 Infarto de miocardio en las últimas 24 semanas. 2.4 Hipertensión no controlada. 2.5 Arritmias cardíacas inestables; Positive for HIV; Has known active hepatitis B or C infection. 5.1 Active hepatitis B is defined as a known positive hepatitis B surface antigen (HbsAg) result. 5.2 Active hepatitis C is defined by a known positive hepatitis C antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the local assay; Has a history of other malignancy within the past 3 years, except for locally curable cancers that have been apparently cured or successfully resected, such as (but not limited to): basal or squamous cell skin cancer, superficial bladder cancer, gastric cancer, or carcinoma in situ of the prostate, cervix, or breast; A known bleeding disorder that is deemed to place the participant at unacceptable risk for bleeding complications from IT injections or biopsies; Women who are breastfeeding or have a positive serum pregnancy test; Prolongación marcada inicial del intervalo QT/QTc (p. ej., demostración repetida de un intervalo QTc >480 ms) (Criterios Terminológicos Frecuentes para la Clasificación de Acontecimientos Adversos [grado 1 de los CTCAE]) utilizando el intervalo QT corregido según la fórmula de Fridericia (QTcF).

EU CTIS 2023-506092-10-00