Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-500 in Metastatic Castration Resistant Prostate Cancer (mCRPC)
Study Details
Study Description
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).
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Part 1 (Monotherapy Dose Escalation): Single-agent AMX-500 dose escalation
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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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Duration of the study up to approximately 48 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: AMX-500 Monotherapy Dose Escalation AMX-500 will be administered as a monotherapy in patients with mCRPC over a 21-day cycle |
Drug: AMX-500
Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion
|
| Experimental: Part 2: AMX-500 Monotherapy Dose Expansion AMX-500 will be administered as a monotherapy in patients with mCRPC over a 21-day cycle |
Drug: AMX-500
Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion
|
Outcome Measures
Primary Outcome Measures
- 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 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 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
- 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 [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: 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: 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: 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: 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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Has metastatic disease, defined by ≥1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging - Has documented progressive mCRPC
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Have been treated with ≥ 1 prior taxane regimens (eg, docetaxel, cabazitaxel)
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Participants deemed unsuitable for standard of care
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Has Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
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Has a life expectancy more than 6 months
Exclusion Criteria:
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Presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
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Has acute or chronic infections
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Has a concomitant medical or inflammatory condition that may increase the risk of toxicity to AMX 500, per the Investigator
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Has lesions in proximity of vital organs
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amunix, a Sanofi Company
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TCD17896
- U1111-1287-6968
- AMX-500-001