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

Phase 1

Recruiting

• Conditions: Locally Advanced or Metastatic HER2-Expressing Cancers
• Interventions: Drug: AMX-818; Drug: pembrolizumab

• Registration Number: NCT05356741
• Lead Sponsor: Amunix, a Sanofi Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-13
• Study First Submitted: 2022-04-26
• Study First Submitted QC: 2022-04-26
• Study First Posted: 2022-05-02
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-06
• Last Update Posted: 2024-06-07
• Primary Completion: 2027-08-16
• Study Completion: 2027-08-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 645

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2 (dose escalation)	pembrolizumab	Participants will receive AMX-818 plus pembrolizumab
Part 1 (dose escalation)	AMX-818	Participants will receive single-agent AMX-818
Part 2 (dose escalation)	AMX-818	Participants will receive AMX-818 plus pembrolizumab
Part 4 (dose expansion	AMX-818	Participants will receive AMX-818 plus pembrolizumab
Part 3 (dose expansion)	AMX-818	Participants will receive single-agent AMX-818
Part 4 (dose expansion	pembrolizumab	Participants will receive AMX-818 plus pembrolizumab

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicity - Part 1 and Part 2	Up to approximately 21 days (Part 1) and 42 days (Part 2)
Objective Response Rate (ORR) - Part 3 and Part 4	Up to approximately 52 months	ORR defined as a Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
Duration of Response (DOR) - Part 3 and Part 4	Up to approximately 52 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.
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

Secondary Outcome Measures

Name	Time	Method
PK parameter: Clearance (CL)	Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
DOR - Part 3 and Part 4	Up to approximately 52 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 iRECIST.
Incidence of anti-drug antibodies (ADAs) to AMX-818	Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 52 months
All parts: Disease control rate (DCR)	Up to approximately 52 months	defined as CR+PR+ Stable Disease (SD) per RECIST v 1.1
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: Volume of distribution at steady-state (Vss)	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
ORR - Part 3 and Part 4	Up to approximately 52 months	ORR defined as defined as a Complete Response (CR) or Partial Response (PR) per Immune Response Evaluation Criteria in Solid Tumors (iRECIST).
PK parameter: Accumulation ratio	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

Trial Locations

Locations (10)

Investigational site number #200; 🇵🇹 Porto, Portugal

Investigational site number #150; 🇫🇷 Toulouse, France

Investigational site number #253; 🇪🇸 Pozuelo de Alarcón, Spain

Investigational site number #252; 🇪🇸 Madrid, Spain

Investigational site number #100; 🇦🇺 Melbourne, Victoria, Australia

Investigational site number #101; 🇦🇺 Randwick, Australia

Investigational site number #255; 🇪🇸 Barcelona, Spain

Investigational site number #251; 🇪🇸 Barcelona, Spain

Investigational site number #254; 🇪🇸 Madrid, Spain

Investigational site number #250; 🇪🇸 Pamplona, Spain