A Phase 1, Multicenter, Open-Label Study of SQZ-AAC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 6
- 主要终点
- Number of participants with dose-limiting toxicity (DLT)
研究概览
简要总结
This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with recurrent, locally advanced or metastatic human papillomavirus strain 16 positive (HPV16+) solid tumors. The study includes patients with anal, rectal, cervical, head and neck, penile, vulvar, or vaginal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Male or female patients ≥18 years of age who are HLA-A*02+ (performed during screening locally or centrally, or based on documented historic test results)
- •Histologically confirmed incurable or metastatic solid tumors that are HPV16+ (performed during screening locally or centrally, or based on documented historic test results)
- •Cancer must have progressed after at least 1 available standard therapy for incurable disease, or the patient is intolerant to or refuses standard therapy(ies) or has a tumor for which no standard therapy(ies) exist
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
- •At least 1 measurable lesion according to RECIST 1.1
- •Must have a lesion that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Baseline and on Cycle 2 Day 8 (+/- 3 days)
- •Patients must agree to venous access for the blood collection for manufacture of autologous blood product and be willing to have a central line inserted if venous access is an issue
- •Adequate organ function and bone marrow reserve performed within 14 days of blood collection for manufacture of autologous blood product
排除标准
- •Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to blood collection for manufacture of autologous blood product. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to Cycle 1 Day 1
- •Systemic treatment with either corticosteroids (>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1
- •Patients treated with non-corticosteroid based immunosuppressive agents within the last 6 months may not be eligible and should be discussed with the Sponsor
- •Patients with active, known, or suspected autoimmune disease may not be eligible and should be discussed with the Sponsor
- •Patients with >Grade 1 AEs related to previous treatment with anticancer or investigational therapy that do not resolve at least 2 weeks prior to blood collection for manufacture of autologous blood product, except Grade 2 alopecia
- •Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection
- •History of any Grade 4 immune-related AE (irAE) from prior immunotherapy
- •Has known active central nervous system metastases
- •History of interstitial lung disease requiring steroids
- •Significant acute or chronic illness
- •Major surgery within 2 weeks of blood collection for manufacture of autologous blood product
研究组 & 干预措施
Part 1 Monotherapy Dose Escalation Phase
In Part 1, SQZ-AAC-HPV as a monotherapy is administered every 3 weeks for up to a year.
There are 3 groups ("Cohorts") in this Phase as follows:
- Cohort 1a: low dose SQZ-AAC-HPV
- Cohort 1b: high dose SQZ-AAC-HPV
- Cohort 1c: higher or lower dose SQZ-AAC-HPV
干预措施: SQZ-AAC-HPV (Biological)
Part 2 Combination Safety Phase
In Part 2, SQZ-AAC-HPV in combination with immune checkpoint inhibitors (1) ipilimumab, (2) nivolumab, or (3) nivolumab plus ipilimumab is administered every 3 weeks up to a year, but the immune checkpoint inhibitors may be administered up to 2 years. There are 3 groups ("Cohorts") in this Phase as follows:
- Cohort 2a: SQZ-AAC-HPV RP2D (Recommended Phase 2 Dose) plus ipilimumab
- Cohort 2b: SQZ-AAC-HPV RP2D plus nivolumab
- Cohort 2c: SQZ-AAC-HPV RP2D plus nivolumab and ipilimumab
干预措施: SQZ-AAC-HPV (Biological)
Part 2 Combination Safety Phase
In Part 2, SQZ-AAC-HPV in combination with immune checkpoint inhibitors (1) ipilimumab, (2) nivolumab, or (3) nivolumab plus ipilimumab is administered every 3 weeks up to a year, but the immune checkpoint inhibitors may be administered up to 2 years. There are 3 groups ("Cohorts") in this Phase as follows:
- Cohort 2a: SQZ-AAC-HPV RP2D (Recommended Phase 2 Dose) plus ipilimumab
- Cohort 2b: SQZ-AAC-HPV RP2D plus nivolumab
- Cohort 2c: SQZ-AAC-HPV RP2D plus nivolumab and ipilimumab
干预措施: Ipilimumab (Drug)
Part 2 Combination Safety Phase
In Part 2, SQZ-AAC-HPV in combination with immune checkpoint inhibitors (1) ipilimumab, (2) nivolumab, or (3) nivolumab plus ipilimumab is administered every 3 weeks up to a year, but the immune checkpoint inhibitors may be administered up to 2 years. There are 3 groups ("Cohorts") in this Phase as follows:
- Cohort 2a: SQZ-AAC-HPV RP2D (Recommended Phase 2 Dose) plus ipilimumab
- Cohort 2b: SQZ-AAC-HPV RP2D plus nivolumab
- Cohort 2c: SQZ-AAC-HPV RP2D plus nivolumab and ipilimumab
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of participants with dose-limiting toxicity (DLT)
时间窗: Through Day 28
For SQZ-AAC-HPV as a monotherapy (Part 1)
Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0
时间窗: Up to 1 year after LPFV (Last Patient, First Visit)
For SQZ-AAC-HPV administered as monotherapy, and in combination with immune checkpoint inhibitors (Part 1 and Part 2, respectively)
Number of participants with DLT
时间窗: Through Day 28
For SQC-AAC-HPV in combination with immune checkpoint inhibitors (Part 2)
次要结局
- Progression-free survival (PFS)(Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product)
- Overall survival (OS)(Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product)
- Best overall Response (BoR)(Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product)
- Disease-control rate (DCR)(Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product)
- Objective response rate (ORR)(Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product)
- Duration of Response (DoR)(Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product)
- Amount of investigational product (IP) from individual patient blood collection - product failures(From leukapheresis through manufacture, a maximum of 28 days)
- Amount of investigational product (IP) from individual patient blood collection - batch yield(From leukapheresis through manufacture, a maximum of 28 days)