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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic HER2-Expressing Cancers
• Intervention / Treatment: Drug: AMX-818; Drug: pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 645
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Australia
  • Melbourne, Australia, 3000
    • Recruiting
    • Investigational site number #100
  • Randwick, Australia, 2031
    • Recruiting
    • Investigational site number #101
• France
  • Toulouse, France, 31059
    • Recruiting
    • Investigational site number #150
• Portugal
  • Porto, Portugal, 4200-072
    • Recruiting
    • Investigational site number #200
• Spain
  • Barcelona, Spain, 08023
    • Recruiting
    • Investigational site number #255
  • Barcelona, Spain, 08035
    • Recruiting
    • Investigational site number #251
  • Madrid, Spain, 28027
    • Recruiting
    • Investigational site number #254
  • Madrid, Spain, 28050
    • Recruiting
    • Investigational site number #252
  • Pamplona, Spain, 31008
    • Recruiting
    • Investigational site number #250
  • Pozuelo de Alarcón, Spain, 28223
    • Recruiting
    • Investigational site number #253

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (dose escalation); Participants will receive single-agent AMX-818	Drug: AMX-818; Administered as IV infusion
Experimental: Part 2 (dose escalation); Participants will receive AMX-818 plus pembrolizumab	Drug: AMX-818; Administered as IV infusion; Drug: pembrolizumab; Administered as IV infusion; Other Names: KEYTRUDA®
Experimental: Part 3 (dose expansion); Participants will receive single-agent AMX-818	Drug: AMX-818; Administered as IV infusion
Experimental: Part 4 (dose expansion; Participants will receive AMX-818 plus pembrolizumab	Drug: AMX-818; Administered as IV infusion; Drug: pembrolizumab; Administered as IV infusion; Other Names: KEYTRUDA®

What is the study measuring?

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)
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
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

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
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
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
All parts: Disease control rate (DCR)	defined as CR+PR+ Stable Disease (SD) per RECIST v 1.1	Up to approximately 52 months

Collaborators and Investigators

• Sponsor: Amunix, a Sanofi Company
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Estimated): December 9, 2026
• Study Completion (Estimated): August 16, 2027

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: AMX-818-001; TCD17730 (Other Identifier: Sanofi Identifier); MK-3475-D14 (Other Identifier: Merck Sharp & Dohme LLC); KEYNOTE-D14 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No