To Access the Safety and Effects of Intravenous Administration of AMX-818 Alone and in Combination With Pembrolizumab in Adult Participants With Locally Advanced or Metastatic HER2-Expressing Cancers

Study Overview
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Brief Summary
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This first-in-human (FIH) Phase 1 open-label multicenter dose-escalation and dose-expansion study is designed to evaluate the safety, pharmacokinetics, and preliminary activity of AMX-818 as a single agent and in combination with pembrolizumab in participants with HER2+ tumors across multiple tumor types. The study will be conducted in four parts: Part 1 (dose escalation): Single-agent AMX-818 Part 2 (dose escalation): AMX-818 plus pembrolizumab Part 3 (dose expansion): Single-agent AMX-818 Part 4 (dose expansion): AMX-818 plus pembrolizumab The total length of the study, from screening of the first participant to the end of the study, is expected to be approximately 52 months.

Official Title
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A Phase 1, Multicenter, Open-Label, First-in-Human Study of the Safety and Pharmacokinetics of AMX-818 Alone and in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers

Conditions
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Locally Advanced or Metastatic HER2-Expressing Cancers

Intervention / Treatment
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* Drug: AMX-818
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Written informed consent by the participant (or legally acceptable representative if applicable) Life expectancy of at least 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Diseases under study, prior lines of therapy, and human epidermal growth factor receptor 2 (HER2) status, per local tests Exclusion criteria: Significant cardiopulmonary disease and recent cardiac events History of major organ autoimmune diseases Acute or chronic infections The above information is not intended to contain all considerations relevant to the 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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All

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 (dose escalation)<br>Participants will receive single-agent AMX-818 | Drug: AMX-818<br>* Administered as IV infusion<br>|
| Experimental: Part 2 (dose escalation)<br>Participants will receive AMX-818 plus pembrolizumab | Drug: AMX-818<br>* Administered as IV infusion<br>Drug: Pembrolizumab<br>* Administered as IV infusion<br>|
| Experimental: Part 3 (dose expansion)<br>Participants will receive single-agent AMX-818 | Drug: AMX-818<br>* Administered as IV infusion<br>|
| Experimental: Part 4 (dose expansion<br>Participants will receive AMX-818 plus pembrolizumab | Drug: AMX-818<br>* Administered as IV infusion<br>Drug: Pembrolizumab<br>* Administered as IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity - Part 1 and Part 2 |  | Up to approximately 21 days (Part 1) and 42 days (Part 2) | 
| Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4 |  | Up to approximately 55 months | 
| Objective Response Rate (ORR) - Part 3 and Part 4 | ORR defined as a Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. | Up to approximately 52 months | 
| Duration of Response (DOR) - Part 3 and Part 4 | 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. | Up to approximately 52 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR - Part 3 and Part 4 | ORR defined as defined as a Complete Response (CR) or Partial Response (PR) per Immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Up to approximately 52 months | 
| DOR - Part 3 and Part 4 | 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 iRECIST. | Up to approximately 52 months | 
| Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC) |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| PK parameter: Maximum plasma concentration (Cmax) |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| PK parameter: Minimum serum concentration (Cmin) |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| PK parameter: Clearance (CL) |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| PK parameter: Volume of distribution at steady-state (Vss) |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| PK parameter: Accumulation ratio |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| PK parameter: Half-life (t1/2) |  | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months | 
| Incidence of anti-drug antibodies (ADAs) to AMX-818 |  | Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 52 months |