Open
Actively Recruiting
AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)
About
Brief Summary
The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor AMG 193 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 AMG 193 administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted thoracic tumors.
Primary Purpose
Study Type
Phase
Eligibility
Gender
Healthy Volunteers
Minimum Age
Maximum Age
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 AMG 193 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 (AMG 193 + carboplatin + paclitaxel + pembrolizumab):
- Predominantly squamous histology. Arm B (AMG 193 + carboplatin + pemetrexed + pembrolizumab):
- Predominantly non-squamous histology. Arm C (AMG 193 + 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 exclusion criteria as defined in the protocol.
- 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 solid organ transplant.
- Major surgery within 28 days of first dose of AMG 193.
- Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
- Radiation therapy within 28 days of first dose. Subprotocol A
- Autoimmune disease or immunodeficiency disease as defined in the protocol'
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Study Stats
Protocol No.
24-5242
Category
Lung Cancer
Principal Investigator
Contact
Location
- UCLA Alhambra
- UCLA Burbank
- UCLA Santa Barbara
- UCLA Santa Monica
- UCLA Torrance
- UCLA Ventura
- UCLA Westwood