Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-500 in Metastatic Castration Resistant Prostate Cancer (mCRPC)

Study Overview
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Brief Summary
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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
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Duration of the study up to approximately 48 months.

Official Title
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A Phase 1, First-in-human Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-500 in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)

Conditions
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Hormone-refractory Prostate Cancer

Intervention / Treatment
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* Drug: AMX-500 (SAR446329)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 2 Has a life expectancy more than 6 months Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: AMX-500 Monotherapy Dose Escalation<br>AMX-500 will be administered as a monotherapy in patients with mCRPC over a 21-day cycle | Drug: AMX-500 (SAR446329)<br>* Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion<br>|
| Experimental: Part 2: AMX-500 Monotherapy Dose Expansion<br>AMX-500 will be administered as a monotherapy in patients with mCRPC over a 21-day cycle | Drug: AMX-500 (SAR446329)<br>* Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants with Adverse Events (AEs) | Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| Part 1: Incidence of Dose Limiting Toxicities (DLTs) | Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | from the Cycle 1(each cycle is 21 days), Day 1 up to Day 21 | 
| Part 2: Prostate-Specific Antigen (PSA) response rate | defined as a ≥ 50% reduction in PSA from baseline | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| Part 2: Objective Response Rate (ORR) | 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) | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Part 1: PSA response rate |  | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| Part 1: Objective Response Rate (ORR) |  | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Time to Response | Time from the start of treatment to the first objective tumor response observed for participants who achieved confirmed Complete Response or Partial Response | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Duration of response (DoR) | 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. | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Progression Free Survival PFS | Time from treatment initiation to disease progression using RECIST v1.1 | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Assessment of PK parameters: Cmax | Maximum plasma concentration observed | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Assessment of PK parameters: AUC | Area under the concentration versus time curve | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Assessment of PK parameters: Tmax | Time to reach Cmax | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 
| All parts: Incidence of baseline anti-drug antibodies (ADAs) to AMX-500 | Incidence of patients with baseline anti-drug antibodies to AMX-500 | 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 | Incidence of patients with treatment emergent anti-drug antibodies to AMX-500 | from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Castration Resistant Prostatic Cancer