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

• ClinicalTrials.gov Identifier: NCT05356741
• Recruitment Status: Recruiting
• First Posted: May 2, 2022
• Last Update Posted: March 8, 2024
• Sponsor: Amunix, a Sanofi Company
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Sanofi ( Amunix, a Sanofi Company )

Tracking Information

• First Submitted Date: April 26, 2022
• First Posted Date: May 2, 2022
• Last Update Posted Date: March 8, 2024
• Actual Study Start Date: April 13, 2022
• Estimated Primary Completion Date: December 9, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2023)

• Incidence of dose-limiting toxicity - Part 1 and Part 2 [ Time Frame: 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 [ Time Frame: Up to approximately 55 months ]
• Objective Response Rate (ORR) - Part 3 and Part 4 [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 26, 2022)

• Incidence of dose-limiting toxicity - Part 1 and Part 2 [ Time Frame: 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 [ Time Frame: Up to approximately 52 months ]
• Objective Response Rate (ORR) - Part 3 and Part 4 [ Time Frame: 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 [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: March 6, 2024)

• ORR - Part 3 and Part 4 [ Time Frame: 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).
• DOR - Part 3 and Part 4 [ Time Frame: 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.
• Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Maximum plasma concentration (Cmax) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Minimum serum concentration (Cmin) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Clearance (CL) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Volume of distribution at steady-state (Vss) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Accumulation ratio [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Half-life (t1/2) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• Incidence of anti-drug antibodies (ADAs) to AMX-818 [ Time Frame: Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 52 months ]
• All parts: Disease control rate (DCR) [ Time Frame: Up to approximately 52 months ]
  defined as CR+PR+ Stable Disease (SD) per RECIST v 1.1

Original Secondary Outcome Measures (submitted: April 26, 2022)

• ORR - Part 3 and Part 4 [ Time Frame: 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).
• DOR - Part 3 and Part 4 [ Time Frame: 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.
• Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months ]
• PK parameter: Maximum plasma concentration (Cmax) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Minimum serum concentration (Cmin) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Clearance (CL) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Volume of distribution at steady-state (Vss) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Accumulation ratio [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• PK parameter: Half-life (t1/2) [ Time Frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months ]
• Incidence of anti-drug antibodies (ADAs) to AMX 818 [ Time Frame: Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 52 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced or Metastatic HER2-Expressing Cancers

Intervention

• Drug: AMX-818
  Administered as IV infusion
• Drug: pembrolizumab
  Administered as IV infusion
  Other Name: KEYTRUDA®

Study Arms

• Experimental: Part 1 (dose escalation)
  Participants will receive single-agent AMX-818
  Intervention: Drug: AMX-818
• Experimental: Part 2 (dose escalation)
  Participants will receive AMX-818 plus pembrolizumab
  Interventions:

  • Drug: AMX-818
  • Drug: pembrolizumab
• Experimental: Part 3 (dose expansion)
  Participants will receive single-agent AMX-818
  Intervention: Drug: AMX-818
• Experimental: Part 4 (dose expansion
  Participants will receive AMX-818 plus pembrolizumab
  Interventions:

  • Drug: AMX-818
  • Drug: pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 6, 2024): 645
• Original Estimated Enrollment (submitted: April 26, 2022): 560
• Estimated Study Completion Date: August 16, 2027
• Estimated Primary Completion Date: December 9, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Trial Transparency email recommended (Toll free for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

• Listed Location Countries: Australia, France, Portugal, Spain

Administrative Information

• NCT Number: NCT05356741
• 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 )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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

• Current Responsible Party: Sanofi ( Amunix, a Sanofi Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: Amunix, a Sanofi Company
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: March 2024