Thoracic Tumors, Non-small Cell Lung Cancer
Conditions
Keywords
Oncology, Methylthioadenosine phosphorylase, AMG 193, PRMT5 inhibitor, MTAP, NSCLC
Brief summary
The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deleted thoracic tumors. The study also aims to determine the safety profile of Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted thoracic tumors.
Interventions
DRUGAnvumetostat
Administered PO
DRUGCarboplatin
Administered IV
DRUGPaclitaxel
Administered IV
DRUGPembrolizumab
Administered IV
DRUGPemetrexed
Administered IV
DRUGSotorasib
Administered PO
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Subprotocol A, B, and C * Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years). * Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before Anvumetostat dosing. * Homozygous MTAP-deletion * Able to swallow and retain PO administered study treatment. * Disease measurable as defined by RECIST v1.1. Subprotocol A - Histologically or cytologically confirmed diagnosis of NSCLC. Arm A (Anvumetostat + carboplatin + paclitaxel + pembrolizumab): \- Predominantly squamous histology. Arm B (Anvumetostat + carboplatin + pemetrexed + pembrolizumab): \- Predominantly non-squamous histology. Arm C (Anvumetostat + pembrolizumab): \- PD-L1 positive. Subprotocol B - Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation. Subprotocol C * Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases. * Brain lesion meeting RANO-BM criteria for measurable disease.
Exclusion criteria
Subprotocol A, B, and C * Cardiovascular and pulmonary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose Limiting Toxicities (DLT) | Up to approximately 21 days | — |
| Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE) | Up to approximately 3 years | TEAEs are any event that occurred after the participant received study treatment. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. A serious TEAE is any untoward medical occurrence in a clinical study participant after first dose irrespective of a causal relationship with the study treatment(s) that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event. |
| Number of Participants Experiencing Serious Adverse Events (SAE) | Up to approximately 3 years | An SAE is defined as any AE that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above. |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | Up to approximately 3 years |
| Disease Control (DC) per RECIST v1.1 | Up to approximately 3 years |
| Duration of Response (DOR) per RECIST v1.1 | Up to approximately 3 years |
| Time to Response (TTR) per RECIST v1.1 | Up to approximately 3 years |
| Overall Survival (OS) per RECIST v1.1 | Up to approximately 3 years |
| Progression-free Survival (PFS) per RECIST v1.1 | Up to approximately 3 years |
| Maximum Plasma Concentration (Cmax) of Anvumetostat | Up to Day 1 of Cycle 5 (one cycle = 21 days) |
| Time to Maximum Plasma Concentration (tmax) of Anvumetostat | Up to Day 1 of Cycle 5 (one cycle = 21 days) |
| Area Under the Plasma Concentration-time Curve (AUC) of Anvumetostat | Up to Day 1 of Cycle 5 (one cycle = 21 days) |
| Intracranial objective response (IOR) per Response Assessment in Neuro Oncology Brain Metastases (RANO-BM ) | Up to approximately 3 years |
| Intracranial Disease Control (IDC) per RANO-BM | Up to approximately 3 years |
| Intracranial Duration of Response (IDOR) per RANO-BM | Up to approximately 3 years |
| Time to Intracranial Radiation Therapy per RANO-BM | Up to approximately 3 years |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, Italy, Japan, Netherlands, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTAmgen Call Center
STUDY_DIRECTORMD
Amgen
Outcome results
None listed