AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).
A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)
Amgen
500 participants
Sep 17, 2024
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria17
- 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 Criteria8
- Subprotocol A, B, and C
- 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'
Interventions
Administered PO
Administered PO
Administered IV
Administered IV
Administered IV
Administered IV
Locations(83)
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NCT06333951