Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-500 in Metastatic Castration Resistant Prostate Cancer (mCRPC)
- Conditions
- Hormone-refractory Prostate Cancer
- Interventions
- Drug: AMX-500 (SAR446329)
- Registration Number
- NCT05997615
- Lead Sponsor
- Amunix, a Sanofi Company
- Brief Summary
The study will be conducted in 4 parts and will commence with dose escalation of AMX-500 as a monotherapy (Part 1), followed by monotherapy dose expansion (Part 2).
* Part 1 (Monotherapy Dose Escalation): Single-agent AMX-500 dose escalation
* Part 2 (Monotherapy Dose Expansion): Single-agent AMX-500 dose expansion
The study may subsequently continue via a protocol amendment with dose escalation of AMX-500 combinations (Part 3) followed by combination therapy dose expansion (Part 4).
- Detailed Description
Duration of the study up to approximately 48 months.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 215
- Has histological, pathological, and/or cytological confirmation of prostate adenocarcinoma OR metastatic disease typical of prostate cancer (ie, involving bone or pelvic lymph nodes or para-aortic lymph nodes)
- Has metastatic disease, defined by ≥1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging - Has documented progressive mCRPC
- Have been treated with ≥ 1 prior taxane regimens (eg, docetaxel, cabazitaxel)
- Participants deemed unsuitable for standard of care
- Has Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Has a life expectancy more than 6 months
- Presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
- Has acute or chronic infections
- Has a concomitant medical or inflammatory condition that may increase the risk of toxicity to AMX 500, per the Investigator
- Has lesions in proximity of vital organs
- Has known active CNS metastases and/or carcinomatous meningitis The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: AMX-500 Monotherapy Dose Escalation AMX-500 (SAR446329) AMX-500 will be administered as a monotherapy in patients with mCRPC over a 21-day cycle Part 2: AMX-500 Monotherapy Dose Expansion AMX-500 (SAR446329) AMX-500 will be administered as a monotherapy in patients with mCRPC over a 21-day cycle
- Primary Outcome Measures
Name Time Method Part 1: Incidence of Dose Limiting Toxicities (DLTs) from the Cycle 1(each cycle is 21 days), Day 1 up to Day 21 Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Part 2: Prostate-Specific Antigen (PSA) response rate from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months defined as a ≥ 50% reduction in PSA from baseline
Part 1: Number of participants with Adverse Events (AEs) from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Part 2: Objective Response Rate (ORR) from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- Secondary Outcome Measures
Name Time Method Part 1: Objective Response Rate (ORR) from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months All parts: Incidence of treatment emergent anti-drug antibodies (ADAs) to AMX-500 from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Incidence of patients with treatment emergent anti-drug antibodies to AMX-500
Part 1: PSA response rate from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months All parts: Duration of response (DoR) from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months DOR defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v.1.1.
All parts: Assessment of PK parameters: Cmax from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Maximum plasma concentration observed
All parts: Assessment of PK parameters: AUC from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Area under the concentration versus time curve
All parts: Incidence of baseline anti-drug antibodies (ADAs) to AMX-500 from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Incidence of patients with baseline anti-drug antibodies to AMX-500
Part 2: Number of participants with Adverse Events (AEs) from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months All parts: Time to Response from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Time from the start of treatment to the first objective tumor response observed for participants who achieved confirmed Complete Response or Partial Response
All parts: Progression Free Survival PFS from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Time from treatment initiation to disease progression using RECIST v1.1
All parts: Assessment of PK parameters: Tmax from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months Time to reach Cmax
Trial Locations
- Locations (8)
Investigational Site Number: 253
🇪🇸Pamplona, Spain
Investigational Site Number: 254
🇪🇸Madrid, Spain
Investigational Site Number: 101
🇦🇺New South Wales, Australia
Investigational Site Number: 300
🇬🇧London, United Kingdom
Investigational Site Number: 251
🇪🇸Barcelona, Spain
Investigational Site Number: 250
🇪🇸Barcelona, Spain
Investigational Site Number: 100
🇦🇺Victoria, Australia
Investigational Site Number: 252
🇪🇸Madrid, Spain