Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors

Phase 1 First-In-Human Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors

The primary objective of this study is to:

• Evaluate the safety and tolerability of AMG 305 in adult participants
• Determine the optimal biologically active dose (OBD), at or below the maximum tolerated dose (MTD) with MTD 1 as the maximum tolerated starting dose and MTD 2 as the maximum tolerated target dose
• Determine the recommended phase 2 dose (RP2D)

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AMG 305

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris Obrien Lifehouse
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
• France
  • Toulouse cedex 9, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitaetsklinikum Dresden
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen
  • Wuerzburg, Germany, 97078
    • Recruiting
    • Universitaetsklinikum Wuerzburg
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario Madrid Sanchinarro
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Recruiting
      • Hospital Clinic i Provincial de Barcelona
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Pre-screening:

• Participant has provided informed consent prior to initiation of any pre screening study specific activities/procedures.
• Participants with histologically or cytologically documented solid tumor diseases expressing cadherin-3 and mesothelin (by mRNA in the Cancer Genome Atlas Program [TCGA] database), including CRC, NSCLC, mesothelioma, pancreatic cancer, gastric cancer, head and neck cancer, cervical carcinoma, uterine carcinoma, and breast cancer

Clinical study:

• Participant has provided inform consent to the main study prior to initiation of any study specific activities/procedures
• Male or female participants age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Participants with histologically or cytologically documented solid tumor diseases, including CRC, NSCLC, mesothelioma, pancreatic cancer, GC, head and neck cancer, cervical carcinoma, uterine carcinoma, and breast cancer. Participants must have exhausted available standard of care (SOC) systemic therapy or must not be candidates for such available therapy
• For dose expansion cohorts: participants with at least 1 measurable lesion ≥10 mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study
• Life expectancy > 3 months
• Adequate organ function

Key Exclusion Criteria:

• Untreated central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
• History of other malignancy within the past 2 years
• Ongoing or active infection
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Known interstitial lung disease
• Positive test for human immunodeficiency virus (HIV)
• Positive hepatitis B surface antigen or positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
• Anticancer therapies including radiotherapy (with the exception of palliative radiation) chemotherapy or molecularly targeted treatments or tyrosine kinase inhibitors (TKI) within 4 weeks or 5 half lives (whichever is longer) of administration of a first dose of study treatment; immunotherapies/monoclonal antibodies within 3 weeks of administration of a first dose of study treatment.
• Has had a major surgery within 4 weeks of administration of a first dose of study treatment
• Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study (eg, ulcerative colitis, Crohn's disease)
• Live and/or live-attenuated vaccines received within 28 days (or longer, if required locally) prior to the first dose of AMG 305
• Currently receiving treatment in another investigational device or drug study
• Female participants of childbearing potential or male participants unwilling to use protocol specified method of contraception
• Females who are pregnant, breastfeeding or who plan to breastfeed or become pregnant while on study
• History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Dose Exploration; Participants will receive escalating doses of AMG 305.	Drug: AMG 305; Short-term intravenous (IV) infusion
Experimental: Part B: Dose Expansion; Participants with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer, and other solid tumors will receive the RP2D identified in Part A.	Drug: AMG 305; Short-term intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who Experience Dose Limiting Toxicities (DLTs)		Day 1 to Day 28
Percentage of Participants who Experience Treatment-Emergent Adverse Events (TEAEs)	Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests, as assessed by the investigator, will also be reported as TEAEs.	Up to a maximum of 2 years
Percentage of Participants who Experience Treatment-Related Adverse Events		Up to a maximum of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Serum Concentration (Cmax) of AMG 305		Up to a maximum of 2 years
Minimum Serum Concentration (Cmin) of AMG 305		Up to a maximum of 2 years
Area Under the Concentration-Time Curve (AUC) of AMG 305		Up to a maximum of 2 years
Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)	ORR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), Clinical Benefit Rate (defined as BOR of CR, PR, or stable disease [SD] with duration of 24 weeks or longer) based on RECIST v1.1.	Up to a maximum of 2 years
ORR based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)	ORR is defined as immune best overall response (iBOR) of immune complete response (iCR) or immune partial response (iPR), Clinical Benefit Rate (defined as iBOR of iCR, iPR, or immune stable disease [iSD] with duration of 24 weeks or longer) based on iRECIST.	Up to a maximum of 2 years
Duration of Response (DOR)	DOR is defined as the time from the first documentation of objective response until the first documentation of disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST.	Up to a maximum of 2 years
Time to Progression	Time to progression is defined as the time rom first AMG 305 dose until the first documentation of radiological disease progression by RECIST v1.1 and iRECIST.	Up to a maximum of 2 years
Progression-Free Survival (PFS)	PFS is defined as the time from first AMG 305 dose until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST.	Up to a maximum of 2 years
Overall Survival (OS) at 1 Year		1 year
OS at 2 Years		2 years

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Estimated): May 13, 2026
• Study Completion (Estimated): January 14, 2027

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 20220073; 2022-502867-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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