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

Phase 2Active Not RecruitingNCT05975073

Amgen53 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria 1. Evidence of homozygous loss of MTAP (null) and/or MTAP deletion. 2. Presence of advanced/metastatic solid tumor not amenable to curative treatment 1. Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists 2. Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy. 3. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product 4. Disease measurable as defined by RECIST v1.1 5. Adequate organ function as defined in the protocol. 6. Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing. Exclusion Criteria 1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor. 2. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease. 3. Cardiovascular and pulmonary exclusion criteria as defined in the protocol. 4. 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) 5. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry. 6. Prior irradiation to \> 25% of the bone marrow 7. 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.

Locations (27)

City of Hope National Medical Center

Duarte, California, United States

Sarah Cannon Research Institute

Denver, Colorado, United States

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: Day 1 up to approximately 2.5 years

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

Time frame: Day 1 up to approximately 2.5 years

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

Time frame: Day 1 up to approximately 2.5 years