A Phase Ib Study Evaluating the Safety and Tolerability of Sipuleucel-T (Sip-T) in Combination With N-803 in Patients With Metastatic Androgen Pathway Modulation Resistant (mAPMR) Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Frequency of dose-limiting toxicities (Cohort 1 only)
研究概览
简要总结
This phase Ib single-center open-label de-escalation study uses a modified 3+3 design to determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of standard of care Sip-T and N-803 in patients with metastatic androgen pathway modulation resistant (mAPMR) prostate cancer. Patients will receive treatment for up to 8 weeks.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed prostate adenocarcinoma.
- •Imaging- or biopsy-proven metastatic disease. May have any type or location of metastases (bone, lymph node, visceral).
- •Prior treatment must include either orchiectomy or luteinizing hormone-releasing agonist or antagonist treatment with documented testosterone ≤ 50 ng/dL.
- •Eligible for standard of care Sipuleucel-T.
- •Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy.
- •At least 18 years of age.
- •ECOG performance status ≤ 2
- •Adequate bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1,500 K/cumm without granulocyte colony-stimulating factor support
- •Platelets ≥ 100,000 K/cumm without transfusion
- •Hemoglobin ≥ 10.0 g/dL
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT) and ALT(SGPT) ≤ 2.5 x IULN
- •Calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault
- •PSA ≤ 200 ng/mL.
- •Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
排除标准
- •Rapidly progressing disease or symptomatic prostate cancer as assessed by the investigator.
- •Prior immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) within the 6 months prior to enrollment.
- •Prior systemic radiotherapy (such as Ra-223, Lu177-PSMA) within the 6 months prior to enrollment. Prior palliative radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment is allowed. Prior definitive radiation therapy for localized prostate cancer is allowed.
- •Prior exposure to Sipuleucel-T.
- •Ongoing systemic immune suppression (oral steroids equivalent to 10 mg daily prednisone or less are allowed; topical, inhaled, and intra-articular steroids are allowed).
- •Currently receiving any other investigational therapeutic or imaging agents.
- •Patients with known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to Sipuleucel-T or N-803 or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
- •HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
- •Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
- •History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
- •Uncontrolled infection with hepatitis A.
研究组 & 干预措施
Cohort 1: Dose level -2: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 6 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.
干预措施: Sipuleucel-T (Biological)
Cohort 1: Dose level 0 Starting dose: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 15 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.
干预措施: Sipuleucel-T (Biological)
Cohort 1: Dose level 0 Starting dose: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 15 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.
干预措施: N803 (Biological)
Cohort 1: Dose level -1: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 10 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.
干预措施: N803 (Biological)
Cohort 1: Dose level -1: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 10 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.
干预措施: Sipuleucel-T (Biological)
Cohort 2: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and recommended phase 2 dose (RP2D) of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day -5 or 5 days before first SIP-T dose.
干预措施: Sipuleucel-T (Biological)
Cohort 1: Dose level -2: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 6 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.
干预措施: N803 (Biological)
Cohort 2: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and recommended phase 2 dose (RP2D) of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day -5 or 5 days before first SIP-T dose.
干预措施: N803 (Biological)
Cohort 3: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and RP2D of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day 37.
干预措施: Sipuleucel-T (Biological)
Cohort 3: N-803 + SIP-T
Patients will receive standard dose (>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and RP2D of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day 37.
干预措施: N803 (Biological)
结局指标
主要结局
Frequency of dose-limiting toxicities (Cohort 1 only)
时间窗: Start of treatment (day 1 dose of Sip-T) through 14 days following the last dose of N-803 (total time up to 44 days)
As assessed via CTCAE v6.0. Dose limiting toxicities will be evaluated according to protocol.
Recommended Phase II Dose (RP2D) (Cohort 1 only)
时间窗: Start of treatment (day 1 dose of Sip-T) through 14 days following the last dose of N-803 for all participants in Cohort 1 (total time up to 44 days)
RP2D is defined as the highest dose of N-803 that has an overall DLT rate of less than 33% in total of 6 patients.
Number of severe (grade 3+) adverse events measured via CTCAE v6.0
时间窗: Start of treatment through 100 days after last dose of N-803 (total time up to 137 days)
Number and type of adverse events measured via CTCAE v6.0
时间窗: Start of treatment through 100 days after last dose of N-803 (total time up to 137 days)
次要结局
- PSA30 Response(Start of treatment to completion of follow-up (up to 26 months))
- PSA50 Response(Start of treatment to completion of follow-up (up to 26 months))
- PSA90 Response(Start of treatment to completion of follow-up (up to 26 months))
- Radiographic progression-free survival (PFS)(Start of treatment to date of progression or death or last follow-up (up to 26 months))
- Failure-free survival (FFS)(Start of treatment to date of any progression events or last follow-up (up to 26 months))
- Time to next therapy (TTNT)(Through completion of follow-up (up to 26 months))
- Overall survival (OS)(Start of treatment to death or last follow-up (up to 26 months))