Phase 1/2, Placebo-Controlled, Randomized Study to Evaluate the Safety, Immune Response & Clinical Activity of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer Who Have Undergone Transurethral Resection of Bladder Tumor (TURBT)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 104
- 试验地点
- 37
- 主要终点
- Phase 1: Safety and Tolerability
研究概览
简要总结
Phase I/II study: Phase 1 is an open-label, safety study, patients who previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1*10^6 cells) HS-410 monotherapy. Phase 2, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1*10^6 cells) or high dose (1*10^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. Patients who do not receive BCG will be enrolled into an open-label, non-randomized group receiving high dose (1*10^7 cells) intradermal HS-410 monotherapy.
详细描述
This study is a two part study: Phase I and Phase II. The Phase 1 portion is an open-label, safety study. Patients will have previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1*10^6 cells) HS-410 monotherapy. In Phase 2, patients will be assigned to treatment groups based on whether they will receive induction BCG in the typical post-TURBT window. If the investigator plans to administer BCG, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1*10^6 cells) or high dose (1*10^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. If patients will not receive BCG, they will be enrolled into an open-label, non-randomized group and receive high dose (1*10^7 cells) intradermal HS-410 monotherapy.
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
- Double (Participant, Investigator)
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
- •Histologically or cytologically confirmed non-muscle invasive bladder cancer [Ta, T1 or Tis (CIS)] that has been removed by transurethral resection
- •Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size > 3cm, early recurrence (<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
- •Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment > 12 months prior to the baseline staging procedure.
- •Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
- •Adequate laboratory parameters
排除标准
- •Human immunodeficiency virus (HIV) infection or immunodeficiency disorders, either primary or acquired
- •Infections or intercurrent illness requiring active therapy
- •Any condition requiring active steroid or other immunosuppressive therapy
- •Active malignancies within the past 12 months except negligible risk of metastasis or death treated with expected curative outcome.
- •Prostate pelvic radiation within the past 12 months
- •Significant cardiac impairment
- •Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
- •Pregnant or nursing
- •Allergy to soy, egg, or peanut products
- •Receiving another investigational agent (30 day wash-out required prior to first dose)
- •Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
- •Prior treatment with a cancer vaccine for this indication
- •Prior vaccination with BCG for tuberculosis disease
- •Prior splenectomy
结局指标
主要结局
Phase 1: Safety and Tolerability
时间窗: Up to 3 years.
To evaluate the safety and tolerability of vesigenurtacel-L
Phase 2: 1-year Disease-Free Survival
时间窗: One year
Arm 1, 2, 3: 1-year DFS in patients with NMIBC treated with BCG in combination with blinded study product (one of two doses of vesigenurtacel-L or placebo) Arm 4: 1-year DFS in patients with NMIBC treat1fv 9 with high dose vesigenurtacel-L monotherapy One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment
次要结局
- Overall Survival, Expressed as the Number of Participants Alive(Up to 3 years)
- Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months(Up to 2 years)
- T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment(Up to 2 years)
- Safety of the Combination of the HS-410 and BCG(Up to 1 year)
- Immunologic Response of PBMCs Via Intracellular Cytokine Staining (ICS) by Flow Cytometry and/or Enzyme-linked Immunosorbent Spot (ELISPOT) on CD8+ Cells After HS-410 Vaccination as Compared to Baseline.(Up to 2 years)
- Safety of the High Dose HS-410 Monotherapy(Up to 3 years.)
- Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months(Up to 2 years)
- Total PBMC Counts by Flow Cytometry(Up to 3 years)
- Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated(Up to 3 years)
- Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months(Up to 2 years)
- Disease-free Survival at 3, 6, 18, and 24 Months(Up to 2 years)
- Tumor Infiltrating Lymphocytes (TILs)(Up to 3 years)
- Overall Disease-free Survival(Up to 3 years)
- Proportion of Patients Undergoing Cystectomy by 12 and 24 Months(Up to 2 years)
- Tumor Antigen Expression(At screening)