MTAP-null Non-Small-Cell Lung Cancer, MTAP-null Solid Tumors
Conditions
Keywords
Oncology, AMG 193, IDE397, anvumetostat
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).
Interventions
DRUGAnvumetostat
Administered PO
DRUGIDE397
Administered PO
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day 1 up to approximately 2.5 years | Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of Anvumetostat | Day 1 pre-dose up to Cycle 5 (Cycle= 21 days) | — |
| Parts 1 and 2: AUC After Single Dose of IDE397 | Day 1 pre-dose up to Cycle 5 (Cycle= 21 days) | — |
| Parts 1 and 2: AUC After Multiple Doses of IDE397 | Day 1 pre-dose up to Cycle 5 (Cycle= 21 days) | — |
| Parts 1: Overall Response per RECIST 1.1 | Day 1 up to end-of-study (EOS) (approximately 2.5 years) | — |
| Parts 1 and 2: Disease Control Rate | Day 1 up to EOS (approximately 2.5 years) | — |
| Parts 1 and 2: Time to Response (TTR) | Day 1 up to EOS (approximately 2.5 years) | — |
| Parts 1 and 2: Duration of Response (DOR) | Day 1 up to EOS (approximately 2.5 years) | — |
| Parts 1 and 2: Duration of Stable Disease | Day 1 up to EOT (approximately 6 months) | — |
| Parts 1 and 2: Progression-free Survival (PFS) | Day 1 up to EOS (approximately 2.5 years) | — |
| Parts 1 and 2: Overall Survival (OS) | Day 1 up to EOS (approximately 2.5 years) | — |
| Part 2: Number of Participants Experiencing TEAEs | Day 1 up to approximately 2.5 years | Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events |
| Part 2: Number of Participants Experiencing SAEs | Day 1 up to approximately 2.5 years | — |
| Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood | Baseline (Day 1) to EOT plus 30 days (approximately 7 months) | — |
Countries
Australia, Canada, Denmark, South Korea, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed