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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 3
- 主要终点
- Major Pathological Response
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Has at least one lesion that is deemed by the investigator to be easily and safely accessible for IT injection.
排除标准
- •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.
研究组 & 干预措施
TransCon TLR7/8 Agonist in combination with pembrolizumab
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
干预措施: TransCon TLR7/8 Agonist (Drug)
TransCon TLR7/8 Agonist in combination with pembrolizumab
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
干预措施: Pembrolizumab (Drug)
TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
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
干预措施: TransCon TLR7/8 Agonist (Drug)
TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
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
干预措施: TransCon IL-2 β/γ (Drug)
Pembrolizumab
Participants receive 2 cycles, once every 3 weeks of pembrolizumab alone as a 30-minute IV infusion
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Major Pathological Response
时间窗: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
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.
次要结局
- Event Free 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)
- Pathological Complete Response(Up to 6 weeks after Cycle 2 (each cycle is 21 days))
- Overall Survival(Up to 5 years)