Clinical trial NCT05356741: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced or Metastatic HER2-Expressing Cancers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-05-02
Enrollment: 645
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of dose-limiting toxicity - Part 1 and Part 2
timeFrame: Up to approximately 21 days (Part 1) and 42 days (Part 2)
measure: Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4
timeFrame: Up to approximately 55 months
measure: Objective Response Rate (ORR) - Part 3 and Part 4
timeFrame: Up to approximately 52 months
measure: Duration of Response (DOR) - Part 3 and Part 4
timeFrame: Up to approximately 52 months
Secondary outcomes:
measure: ORR - Part 3 and Part 4
timeFrame: Up to approximately 52 months
measure: DOR - Part 3 and Part 4
timeFrame: Up to approximately 52 months
measure: Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC)
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: PK parameter: Maximum plasma concentration (Cmax)
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: PK parameter: Minimum serum concentration (Cmin)
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: PK parameter: Clearance (CL)
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: PK parameter: Volume of distribution at steady-state (Vss)
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: PK parameter: Accumulation ratio
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: PK parameter: Half-life (t1/2)
timeFrame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 52 months
measure: Incidence of anti-drug antibodies (ADAs) to AMX-818
timeFrame: Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 52 months
measure: All parts: Disease control rate (DCR)
timeFrame: Up to approximately 52 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Investigational site number #100
state: Victoria
city: Randwick
country: Australia
facility: Investigational site number #101
city: Toulouse
country: France
facility: Investigational site number #150
city: Porto
country: Portugal
facility: Investigational site number #200
city: Barcelona
country: Spain
facility: Investigational site number #255
city: Barcelona
country: Spain
facility: Investigational site number #251
city: Madrid
country: Spain
facility: Investigational site number #254
city: Madrid
country: Spain
facility: Investigational site number #252
city: Pamplona
country: Spain
facility: Investigational site number #250
city: Pozuelo de Alarcón
country: Spain
facility: Investigational site number #253
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: