NCT 06333951
Brief Summary
The study aims to determine maximum tolerated dosethe amount of medication taken (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 advancedat a late stage, far along 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.
Intervention / Treatment
- Drug: AMG 193
- Drug: Carboplatin
- Drug: Paclitaxel
- Drug: Pembrolizumab
- Drug: Pemetrexed
- Drug: Sotorasib
Inclusion Criteria
Subprotocol A, B, and C
- Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
- Tumor tissuea group of cells that work together to perform a function (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 biopsyremoval of a section of tissue to analyse for cancer cells 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 diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results 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.