A Phase 3 Multicenter, Randomized, Open-label Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab Versus Standard of Care in the First-line Treatment of Patients With Locoregional Recurrence of Squamous Cell Carcinoma of the Head and Neck (HNSCC) With No Distant Metastases
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 412
- 试验地点
- 22
- 主要终点
- Overall survival (OS)
研究概览
简要总结
The goal of this clinical trial is to learn if ASP-1929 photoimmunotherapy (PIT) in combination with pembrolizumab works to treat recurrent squamous cell cancer of the head and neck (HNSCC) with no distant metastases. It will also learn about the safety of ASP-1929 PIT in combination with pembrolizumab.
Researchers will compare ASP-1929 PIT in combination with pembrolizumab to pembrolizumab alone or pembrolizumab plus chemotherapy (carboplatin or cisplatin, plus 5-fluorouracil or paclitaxel or docetaxel) according to physician's choice (control arm).
The overall primary study hypothesis being tested is whether ASP-1929 PIT plus pembrolizumab combination treatment improves the overall survival (OS) of the population defined by the inclusion/exclusion criteria over the control arm.
详细描述
This is a phase 3 multicenter, randomized study designed to evaluate the efficacy and safety of ASP-1929 photoimmunotherapy (PIT) in combination with pembrolizumab versus pembrolizumab-based standard of care (SOC) as first-line treatment of locoregional recurrent HNSCC in patients with no distant metastases.
Patients will be enrolled into the study starting with 3 treatment arms, ASP-1929 PIT at doses of 320 mg/m^2 or 640 mg/m^2 in combination with pembrolizumab treatment arms or a SOC treatment arm in which patients may receive pembrolizumab alone or pembrolizumab plus chemotherapy according to physician's choice.
Treatment assignment within the SOC treatment arm will be based on the decision of the site investigator. To ensure that the SOC treatment arm is appropriately balanced, a 50% enrollment cap will be imposed on pembrolizumab monotherapy and pembrolizumab plus chemotherapy, so that approximately the same number of patients will have been treated within each category.
At the start of the study all patients will be randomized 2:2:1 ratio to ASP-1929 PIT 320 mg/m^2 plus pembrolizumab versus ASP-1929 PIT 640 mg/m^2 plus pembrolizumab versus SOC (pembrolizumab alone or pembrolizumab plus chemotherapy according to physician's choice).
An interim analysis (IA) will be conducted for this study as part of the dose optimization process. Patient enrollment will continue during the period of preparation and conduct of this IA. Based on the findings from the first interim analysis (IA1), the Sponsor will have the option to close one of the two ASP-1929 PIT treatment arms for enrollment. The final decision on the optimized ASP-1929 PIT dose for this study will be made in agreement with the US Food and Drug Administration (FDA).
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
- •Histological or cytological evidence of squamous cell carcinoma of a head and neck primary site (per American Joint Committee on Cancer [AJCC], other than nasopharynx or cuSCC).
- •Appropriate for SOC first-line treatment of their recurrent head and neck cancer with pembrolizumab ± chemotherapy.
- •No known history of any distant metastatic disease (M1 by AJCC eighth edition).
- •Tumors with at least one PIT-accessible and RECIST 1.1 measurable lesion as assessed by investigator.
- •Anti-PD-1 and anti-PD-L1-treatment naïve.
- •Combined positive score (CPS) ≥ 1 as determined locally by an FDA-approved test
- •Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of screening
- •Adequate hematologic, renal, and hepatic organ function
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and must be willing to use a highly effective birth control while on study or be surgically sterile or abstain from heterosexual sexual activity for the course of the study through 180 days after the last dose of study treatment. Male patients must agree to use a highly effective method of contraception starting with the first dose of study medication through 120 days after the last dose of study treatment.
排除标准
- •Diagnosed and/or treated for additional malignancy within 2 years before randomization except for those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). Patients with a history of other prior cancer treated with complete surgical resection and with no evidence of disease may be eligible based on discussion with the Medical Monitor.
- •History of significant (Grade ≥ 3) cetuximab infusion reactions
- •Prior allogeneic tissue/solid organ transplant
- •Known or active central nervous system metastases and/or carcinomatous meningitis
- •Life expectancy of less than 3 months
- •Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- •Evidence of interstitial lung disease or current active, noninfectious pneumonitis
- •Active infection requiring systemic therapies such as antibiotic, antifungal, or antiviral intervention
- •Known or active bacterial, viral, or fungal infection including tuberculosis, Hepatitis B (e.g., HBV DNA is detected), or Hepatitis C (e.g., RNA [qualitative] is detected)
- •Known history of testing positive for human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS)-related illness
- •Prior or ongoing Grade ≥ 3 tumor hemorrhage within 12 weeks of randomization
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Prior systemic chemotherapy or targeted small molecule therapy or radiation therapy within 2 weeks of C1D1 or has not recovered (i.e., Grade ≤ 1 or at baseline) from adverse events (AEs) due to previously administered agent
- •Prior anticancer monoclonal antibody therapy or investigational agent or intervention within 4 weeks of C1D1 or has not recovered (i.e., Grade ≤ 1 or at baseline) from AEs due to previously administered agent
- •Prior receipt of ASP-1929 at any time
- •Receiving chronic systemic steroid therapy (in doses exceeding 10 mg per day of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to randomization
- •Received a live vaccine within 4 weeks of randomization; seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
- •Requiring future examinations or treatments within 4 weeks after an ASP-1929 PIT treatment exposing the patient to significant light (e.g., eye examinations, surgical procedures, endoscopy) that is unrelated to the ASP-1929 PIT treatment
- •Major surgery or significant traumatic injury within 4 weeks before randomization, or anticipation of the need for major surgery during the course of study treatment
研究组 & 干预措施
320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab
ASP-1929 320 mg/m^2 IV infusion followed by illumination with 690 nm red light at accessible tumor sites using the investigational PIT690 Laser System (24 ± 4 hours after end of ASP-1929 infusion). Treatment with ASP-1929 PIT will be repeated every 4 to 6 weeks depending on clinical judgement of investigators.
Pembrolizumab: 200 mg every 3 weeks (Q3W) IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab dosing regimen can be converted from 200 mg Q3W to 400 mg every 6 weeks (Q6W) at the investigator's discretion.
Treatment in the experimental arm will start with the infusion of pembrolizumab on Cycle 1 Day 1 (C1D1) after which ASP-1929 Photoimmunotherapy will follow 7 days later, on Treatment 1 Day 1 (T1D1). Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 24 months.
干预措施: ASP-1929 Photoimmunotherapy (Combination Product)
320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab
ASP-1929 320 mg/m^2 IV infusion followed by illumination with 690 nm red light at accessible tumor sites using the investigational PIT690 Laser System (24 ± 4 hours after end of ASP-1929 infusion). Treatment with ASP-1929 PIT will be repeated every 4 to 6 weeks depending on clinical judgement of investigators.
Pembrolizumab: 200 mg every 3 weeks (Q3W) IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab dosing regimen can be converted from 200 mg Q3W to 400 mg every 6 weeks (Q6W) at the investigator's discretion.
Treatment in the experimental arm will start with the infusion of pembrolizumab on Cycle 1 Day 1 (C1D1) after which ASP-1929 Photoimmunotherapy will follow 7 days later, on Treatment 1 Day 1 (T1D1). Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 24 months.
干预措施: Pembrolizumab (Biological)
640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab
ASP-1929 640 mg/m^2 IV infusion followed by illumination with 690 nm red light at accessible tumor sites using the investigational PIT690 Laser System (24 ± 4 hours after end of ASP-1929 infusion). Treatment with ASP-1929 PIT will be repeated every 4 to 6 weeks depending on clinical judgement of investigators.
Pembrolizumab: 200 mg every 3 weeks (Q3W) IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab dosing regimen can be converted from 200 mg Q3W to 400 mg every 6 weeks (Q6W) at the investigator's discretion.
Treatment in the experimental arm will start with the infusion of pembrolizumab on Cycle 1 Day 1 (C1D1) after which ASP-1929 Photoimmunotherapy will follow 7 days later, on Treatment 1 Day 1 (T1D1). Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 24 months.
干预措施: ASP-1929 Photoimmunotherapy (Combination Product)
640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab
ASP-1929 640 mg/m^2 IV infusion followed by illumination with 690 nm red light at accessible tumor sites using the investigational PIT690 Laser System (24 ± 4 hours after end of ASP-1929 infusion). Treatment with ASP-1929 PIT will be repeated every 4 to 6 weeks depending on clinical judgement of investigators.
Pembrolizumab: 200 mg every 3 weeks (Q3W) IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab dosing regimen can be converted from 200 mg Q3W to 400 mg every 6 weeks (Q6W) at the investigator's discretion.
Treatment in the experimental arm will start with the infusion of pembrolizumab on Cycle 1 Day 1 (C1D1) after which ASP-1929 Photoimmunotherapy will follow 7 days later, on Treatment 1 Day 1 (T1D1). Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 24 months.
干预措施: Pembrolizumab (Biological)
Pembrolizumab or pembrolizumab + chemotherapy (Control)
Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options:
- Pembrolizumab alone
- Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel)
Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion.
Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
5-FU: 1000 mg/m^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles
Paclitaxel: At investigator's choice, 100 mg/m^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles
Docetaxel: 75 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
干预措施: Pembrolizumab (Biological)
Pembrolizumab or pembrolizumab + chemotherapy (Control)
Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options:
- Pembrolizumab alone
- Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel)
Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion.
Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
5-FU: 1000 mg/m^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles
Paclitaxel: At investigator's choice, 100 mg/m^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles
Docetaxel: 75 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
干预措施: Carboplatin (Drug)
Pembrolizumab or pembrolizumab + chemotherapy (Control)
Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options:
- Pembrolizumab alone
- Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel)
Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion.
Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
5-FU: 1000 mg/m^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles
Paclitaxel: At investigator's choice, 100 mg/m^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles
Docetaxel: 75 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
干预措施: Cisplatin (Drug)
Pembrolizumab or pembrolizumab + chemotherapy (Control)
Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options:
- Pembrolizumab alone
- Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel)
Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion.
Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
5-FU: 1000 mg/m^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles
Paclitaxel: At investigator's choice, 100 mg/m^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles
Docetaxel: 75 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
干预措施: 5-fluorouracil (Drug)
Pembrolizumab or pembrolizumab + chemotherapy (Control)
Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options:
- Pembrolizumab alone
- Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel)
Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion.
Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
5-FU: 1000 mg/m^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles
Paclitaxel: At investigator's choice, 100 mg/m^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles
Docetaxel: 75 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
干预措施: Paclitaxel (Drug)
Pembrolizumab or pembrolizumab + chemotherapy (Control)
Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options:
- Pembrolizumab alone
- Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel)
Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion.
Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
5-FU: 1000 mg/m^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles
Paclitaxel: At investigator's choice, 100 mg/m^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles
Docetaxel: 75 mg/m^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles
干预措施: Docetaxel (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: Up to approximately 48 months
OS is defined as the time from randomization until death due to any cause.
次要结局
- Complete response rate (CRR) per modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) as assessed by central reviewer(Up to approximately 48 months)
- Overall response rate (ORR) per modified RECIST 1.1 as assessed by central reviewer(Up to approximately 48 months)
- Proportion of treatment-related adverse events (TRAEs) by CTCAE v5.0(Up to approximately 48 months)
- Proportion of serious adverse events (SAEs) by CTCAE v5.0(Up to approximately 48 months)
- Quality of Life assessment: EORTC Core Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30)(Up to approximately 28 months)
- Presence of anti-drug antibodies (ADAs) (Experimental Arm Only)(Before the start of 1st ASP-1929 infusion, 15 days after end of 1st infusion; same timepoints for 2nd ASP-1929 infusion)
- Progression-free survival (PFS) per modified RECIST 1.1 as assessed by central reviewer(Up to approximately 48 months)
- Duration of CR per modified RECIST 1.1 as assessed by central reviewer(Up to approximately 48 months)
- Time to response (TTR)(Up to approximately 25 months)
- Proportion of treatment-emergent adverse events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) v5.0(Up to approximately 48 months)
- Population pharmacokinetics (PK) - Clearance (Experimental Arm Only)(Before the start of 1st ASP-1929 infusion, 0.25 hours, 4 hours, 24 hours, 192 hours, 360 hours after end of 1st infusion; same timepoints for 2nd ASP-1929 infusion)
- OS rates at 12, 18, and 24 months(12, 18, and 24 months)
- Duration of Response (DOR) per modified RECIST 1.1 as assessed by central reviewer(Up to approximately 48 months)
- CRR from randomization to End of Treatment as assessed by the central reviewer(Up to approximately 25 months)
- Quality of Life assessment: EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-H&N35)(Up to approximately 28 months)