A phase Ib/II open-label, multi-center study of the DNA protein kinase inhibitor AMO959 with lutetium (177Lu) vipivotide tetraxetan (AAA617) in combination with an androgen receptor pathway inhibitor (ARPI) in adult participants with PSMA-positive metastatic castration resistant prostate cancer (mCRPC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 73
- 试验地点
- 18
- 主要终点
- Incidence of dose limiting toxicities (DLTs) with AMO959 in combination with AAA617 +/- ARPI during the first cycle (42 days from first dose of AAA617) of combination treatment
研究概览
简要总结
Phase Ib: Escalation •To characterize the safety and tolerability of AMO959 in combination with AAA617 + ARPI and to determine the Recommended Dose for Expansion (RDE) Phase II •To evaluate the preliminary efficacy of AMO959 in combination with AAA617 + ARPI.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Participants must be adults ≥ 18 years of age.
- •Participants must have an ECOG performance status of 0 to
- •Participants must have histologically confirmed adenocarcinoma of the prostate. Participants with other histology (e.g. neuroendocrine, intraductal subtype) are not eligible.
- •Phase Ib: Prior exposure of up to 1 line of taxane-based chemotherapy is permissible (see Section 5.1 for further details). Phase II: Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
- •Participants must have PSMA-PET positive disease assessed by using a PSMA imaging agent that is approved as per protocol and are eligible as determined by the sponsor’s central reading rules.
- •Castration level of testosterone (< 50 ng/dL]), and/or use of concomitant androgen deprivation therapy ADT
- •Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting (and did not progress on more than one ARPI), based on at least 1 of the following criteria: • Serum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines. • Soft-tissue progression defined PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016). • Progression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria Scher et al 2016).
排除标准
- •Concurrent local (radiation therapy to the prostate with curative intent or other prostate antineoplastic ablative procedures) or systemic ( chemotherapy, immunotherapy, XXX RLTs) antineoplastic treatments, within 28 days of study treatment (Phase Ib) or randomization (Phase II)) or randomization (Phase II), with the exception of ARPIs as further detailed in Section 5.
- •Prior treatment with any RLT or PSMA-targeted agents (approved or investigational)
- •Any other investigational agents within 28 days prior to first dose of any study treatment
- •Concurrent serious medical conditions that may interfere with study procedures or follow-up
- •Participants with a history of CNS metastases must have received therapy (surgery, whole brain radiation therapy, stereotactic radiosurgery) and be neurologically stable, asymptomatic, and not taking corticosteroids for the purpose of maintaining neurologic integrity.
研究组 & 干预措施
AMO959, AMO959
干预措施: AMO959 (Drug)
ENZALUTAMIDE
干预措施: ENZALUTAMIDE (Drug)
Abiraterone
干预措施: Abiraterone (Drug)
GOZETOTIDE
干预措施: GOZETOTIDE (Drug)
RELUGOLIX
干预措施: RELUGOLIX (Drug)
Enzalutamide
干预措施: Enzalutamide (Drug)
Pluvicto 1 000 MBq/mL solution for injection/infusion
干预措施: Pluvicto 1 000 MBq/mL solution for injection/infusion (Drug)
PIFLUFOLASTAT (18F)
干预措施: PIFLUFOLASTAT (18F) (Drug)
Prednison acis 5 mg, Prednison 5 mg GALEN® Tabletten
干预措施: Prednison acis 5 mg (Drug)
Prednison acis 5 mg, Prednison 5 mg GALEN® Tabletten
干预措施: Prednison 5 mg GALEN® Tabletten (Drug)
DEGARELIX, DEGARELIX
干预措施: DEGARELIX (Drug)
ABIRATERONE
干预措施: ABIRATERONE (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs) with AMO959 in combination with AAA617 +/- ARPI during the first cycle (42 days from first dose of AAA617) of combination treatment
Incidence of dose limiting toxicities (DLTs) with AMO959 in combination with AAA617 +/- ARPI during the first cycle (42 days from first dose of AAA617) of combination treatment
Safety: Type, incidence and severity of AEs and SAEs, changes in laboratory values, and vital signs, and deaths
Safety: Type, incidence and severity of AEs and SAEs, changes in laboratory values, and vital signs, and deaths
Tolerability: Incidence of dose interruptions, reductions, and discontinuation; dose intensity and duration of exposure
Tolerability: Incidence of dose interruptions, reductions, and discontinuation; dose intensity and duration of exposure
Biochemical response (PSA50), defined as the proportion of participants who achieved a ≥ 50% decrease in PSA from baseline at any time during the treatment period prior to start of new anti-cancer therapy that is confirmed by a second PSA measurement ≥ 4 weeks later.
Biochemical response (PSA50), defined as the proportion of participants who achieved a ≥ 50% decrease in PSA from baseline at any time during the treatment period prior to start of new anti-cancer therapy that is confirmed by a second PSA measurement ≥ 4 weeks later.
次要结局
- PSA90 is defined as the proportion of participants who achieved a ≥ 90% decrease from baseline at any time during the treatment period prior to start of new anti-cancer therapy that is confirmed by a second PSA measurement ≥ 4 weeks. Only for Phase Ib: PSA50 defined as above Only for Phase II: PSA50 in the AAA617 + ARPI arm as defined above
- rPFS: time from start of study treatment/randomization to radiographic PD/death ORR: proportion of participants with CR/PR DCR: proportion of participants with CR, PR, SD, Non-CR/Non-PD DoR: time from CR/PR to PD/death TTSTP: time from randomization to soft tissue PD OS: time from start of study treatment/randomization to death
- Plasma concentrations of AMO959 over time and derived PK parameters.
- Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data
- Time activity curves (TACs) and absorbed radiation doses in selected organs and tumor lesions.
- Safety: Type, incidence and severity of AEs and SAEs, changes in laboratory values, and vital signs, and deaths. Tolerability: Incidence of dose interruptions, reductions, and discontinuation; dose intensity and duration of exposure.
- rPFS-PET is defined as the time from the date of randomization to first documented radiographic disease progression (an increase in PSMA-positive tumor volume ≥ 20% from baseline and new PSMA-positive malignant lesions) as assessed by BICR using PSMA PET/CT imaging (Seifert et al 2023, Gafita et al 2023) or death due to any cause, whichever occurs first.
- Change from baseline in FACT-P Prostate Cancer Subscale (PCS) Time to worsening on the Worst Pain defined as the time from the date of randomization to the first occurrence of worsening on the Brief Pain Inventory – Short Form (BPI-SF) Worst Pain item of at least 30% increase from baseline or a minimum of 2 points increase from baseline or death due to any cause, whichever occurs first.
- TTSSE defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first.
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG