A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 6
- 主要终点
- Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
研究概览
简要总结
This study is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of immunotherapy combinations in participants with mCRPC who have received prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).
详细描述
This is an open-label, non-randomized, exploratory platform protocol designed to assess the safety and antitumor activity of multiple immunotherapy combinations in participants with mCRPC who have received prior therapy. The platform study will consist of 2 stages: Stage 1, an initial stage to evaluate safety, biomarkers, and clinical activity of a combination and Stage 2, an expanded cohort, when warranted, based on the safety, clinical activity, and/or biomarker results from Stage 1. The Sponsor intends to modify and/or add new combinations to the protocol as data emerge from this and other trials.
Participants must provide consent for archival tissue from a prior biopsy or surgery for prostate cancer and must consent to baseline and on-treatment biopsies, if medically feasible. Participants will be assigned to receive one of the enrolling combination study interventions and will be monitored for safety and response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Metastatic castration resistant prostate cancer with castrate-level testosterone (< 50 ng/dL) at screening.
- •Disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
- •Provide fresh pre-treatment core needle or incisional biopsy of a metastatic tumor lesion not previously irradiated. Fine needle aspiration is not acceptable.
- •Additionally, if a pre-treatment biopsy is not medically feasible for participants with bone only disease, formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be provided.
- •For all participants, in addition to fresh pre-treatment biopsy, consent for archival tissue is required.
- •Must be willing to undergo tumor biopsy(ies) on treatment, if medically feasible.
- •Have received and progressed on prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).
- •Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of prostate-specific antigen (PSA) decline after washout.
- •Bicalutamide: Washout period at least 6 weeks
- •Flutamide and nilutamide: Washout period at least 4 weeks
- •Participants must discontinue therapies for mCRPC for 5 half-lives or 28 days, whichever is shorter.
- •Participants will remain on gonadotropin-releasing hormone (GnRH) agents throughout this study.
- •Prior chemotherapy is allowed if no progression of disease on chemotherapy as defined by PCWG3-modified RECIST 1.
- •Prior treatment with sipuleucel-T, radium-223, or poly ADP ribose polymerase (PARP) inhibitor (eg, olaparib) is allowed.
- •Tissue biopsy may be performed during washout period.
排除标准
- •Has a diagnosis of immunodeficiency or conditions that need systemic corticosteroid replacement therapy > 10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study intervention. Inhaled steroids are permitted if necessary.
- •Has any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll.
- •Has a known history of active TB (Bacillus Tuberculosis).
- •Has known history of, or any evidence of active, non-infectious pneumonitis.
- •Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or hepatitis C virus representing acute or chronic disease.
- •Has received a live vaccine within 30 days of planned start of study intervention.
- •Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study intervention. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
研究组 & 干预措施
Cohort C: CDX-301 + INO-5151 + Nivolumab
干预措施: Cellectra 2000 (Device)
Cohort A: NKTR-214 + Nivolumab
干预措施: NKTR-214 (Cohort A) (Drug)
Cohort A: NKTR-214 + Nivolumab
干预措施: Nivolumab (Cohort A, B and C) (Drug)
Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
干预措施: Nivolumab (Cohort A, B and C) (Drug)
Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
干预措施: Stereotactic body radiation therapy (SBRT) (Cohort B) (Radiation)
Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
干预措施: CDX-301 (Cohort B and C) (Drug)
Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
干预措施: Poly-ICLC (Cohort B) (Drug)
Cohort C: CDX-301 + INO-5151 + Nivolumab
干预措施: Nivolumab (Cohort A, B and C) (Drug)
Cohort C: CDX-301 + INO-5151 + Nivolumab
干预措施: CDX-301 (Cohort B and C) (Drug)
Cohort C: CDX-301 + INO-5151 + Nivolumab
干预措施: INO-5151 (Cohort C) (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
时间窗: For AEs, from initiation of study drug through 100 days after last dose, up to 24 months. For SAEs, from signing informed consent (prior to Screening) through 100 days after last dose, up to 24 months.
An AE is any event that either occurs after the initiation of study drug, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, regardless of its relation to the drug. An SAE is any AE that suggests a significant hazard, contraindication, side effect, or untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Investigators recorded AEs during each participant interaction. Prior to initiation of study drug, only SAEs that were related to a protocol-mandated intervention were recorded. The AE row includes all participants who experienced at least one AE, including SAEs.
次要结局
- Composite Response Rate (CRR)(Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months)
- Disease Control Rate (DCR)(Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months)
- Radiographic Progression-free Survival (rPFS)(Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months)
- Overall Survival (OS)(From initiation of study drug until death due to any cause, up to 2.5 years)
- Overall Survival (OS) at 12 Months(At 12 months)