A Phase 1/2 Study of Anvumetostat in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors

NCT05975073 | Completed Phase 1 FDA Drug

• 1 other identifier: 20220127
• Study Type: interventional
• Target: 53
• Locations: 7 countries
• Sites: 27

Brief Summary

The main aims of this study are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or the recommended combination dose of Anvumetostat in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors, and to evaluate the preliminary anti-tumor activity of anvumetostat in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).

Conditions

MTAP-null Non-Small-Cell Lung Cancer; MTAP-null Solid Tumors

Keywords

Oncology; AMG 193; IDE397; anvumetostat

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  Day 1 up to Day 21

• Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events

  Day 1 up to approximately 2.5 years

• Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)

  Day 1 up to approximately 2.5 years

• Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Day 1 up to approximately 2.5 years

Secondary Outcomes (18)

• Part 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat

  Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)

• Part 1 and 2: Cmax of IDE397

  Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)

• Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat

  Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)

• Part 1 and 2: Tmax of IDE397

  Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)

• Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of Anvumetostat

  Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)

Study Arms (2)

Part 1: Dose Exploration of Anvumetostat Combined With IDE397

EXPERIMENTAL

Participants will receive escalating doses of Anvumetostat and IDE397 administered orally (PO) in cycles of 21 days.

Drug: Anvumetostat; Drug: IDE397

Part 2: Dose Expansion of Anvumetostat Combined With IDE397

EXPERIMENTAL

Anvumetostat and IDE397 will be administered PO in cycles of 21 days.

Drug: Anvumetostat; Drug: IDE397

Interventions

IDE397 DRUG

Administered PO

Part 1: Dose Exploration of Anvumetostat Combined With IDE397; Part 2: Dose Expansion of Anvumetostat Combined With IDE397

Anvumetostat DRUG

Administered PO

Also known as: AMG 193

Part 1: Dose Exploration of Anvumetostat Combined With IDE397; Part 2: Dose Expansion of Anvumetostat Combined With IDE397

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of homozygous loss of MTAP (null) and/or MTAP deletion.
• Presence of advanced/metastatic solid tumor not amenable to curative treatment
• Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists
• Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy.
• Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product
• Disease measurable as defined by RECIST v1.1
• Adequate organ function as defined in the protocol.
• Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.

You may not qualify if:

• Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
• Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease.
• Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis)
• History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry.
• Prior irradiation to \> 25% of the bone marrow
• Use of prescription medications that are known strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5 inducers or 5 half-lives, whichever is longer, prior to any dose of investigational medical product.

Sponsors & Collaborators

• Amgen: lead

Study Sites (27)

City of Hope National Medical Center

Duarte, California, 91090, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana, 46250, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Health Partners Cancer Center at Regions Hospital

Saint Paul, Minnesota, 55102, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

New York University Grossman School of Medicine and New York University Langone Hospitals

New York, New York, 10016, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Prisma Health Upstate

Greenville, South Carolina, 29605, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology

Irving, Texas, 75039, United States

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Neoplasms

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: August 3, 2023
• Study Start: August 1, 2023
• Primary Completion: February 25, 2026
• Study Completion: March 26, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

KR (4); CA (2); TW (2); US (14); ES (2); AU (2); DK (1)