Clinical trial NCT05997615: Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-500 in Metastatic Castration Resistant Prostate Cancer (mCRPC)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hormone-refractory Prostate Cancer
Keywords: Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Castration Resistant Prostatic Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-08-18
Enrollment: 215
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 1
* 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.

Primary outcomes:
measure: Part 1: Number of participants with Adverse Events (AEs)
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: Part 1: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to Day 21
measure: Part 2: Prostate-Specific Antigen (PSA) response rate
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: Part 2: Objective Response Rate (ORR)
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
Secondary outcomes:
measure: Part 2: Number of participants with Adverse Events (AEs)
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: Part 1: PSA response rate
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: Part 1: Objective Response Rate (ORR)
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Time to Response
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Duration of response (DoR)
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Progression Free Survival PFS
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Assessment of PK parameters: Cmax
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Assessment of PK parameters: AUC
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Assessment of PK parameters: Tmax
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Incidence of baseline anti-drug antibodies (ADAs) to AMX-500
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
measure: All parts: Incidence of treatment emergent anti-drug antibodies (ADAs) to AMX-500
timeFrame: from the Cycle 1(each cycle is 21 days), Day 1 up to approximately 48 months
Other outcomes:
Locations:
city: New South Wales
country: Australia
facility: Investigational Site Number: 101
city: Victoria
country: Australia
facility: Investigational Site Number: 100
city: Barcelona
country: Spain
facility: Investigational Site Number: 251
city: Barcelona
country: Spain
facility: Investigational Site Number: 250
city: Madrid
country: Spain
facility: Investigational Site Number: 254
city: Madrid
country: Spain
facility: Investigational Site Number: 252
city: Pamplona
country: Spain
facility: Investigational Site Number: 253
city: London
country: United Kingdom
facility: Investigational Site Number: 300
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: