AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).

Amgen

Status and phase: Enrolling; Phase 1

Conditions: Non-small Cell Lung Cancer; Thoracic Tumors

Treatments: Drug: Carboplatin; Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Sotorasib; Drug: AMG 193; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT06333951

20230167

Details and patient eligibility

About

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.

Enrollment: 500 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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'

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 5 patient groups

Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A

Experimental group

Description:

Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)

Treatment:

Drug: Paclitaxel

Drug: AMG 193

Drug: Pembrolizumab

Drug: Carboplatin

Subprotocol A: NSCLC Arm B

Experimental group

Description:

Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 PO and carboplatin, pemetrexed, and pembrolizumab IV

Treatment:

Drug: AMG 193

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin

Subprotocol A: NSCLC Arm C

Experimental group

Description:

Participants with MTAP-deleted NSCLC will receive a combination of AMG 193 PO and pembrolizumab IV

Treatment:

Drug: AMG 193

Drug: Pembrolizumab

Subprotocol B: NSCLC With KRasG12C Mutation

Experimental group

Description:

Participants with MTAP-deleted NSCLC and KRasG12C mutation will receive a combination of AMG 193 and sotorasib PO

Treatment:

Drug: AMG 193

Drug: Sotorasib

Subprotocol C: NSCLC With Brain Metastases

Experimental group

Description:

Participants with MTAP-deleted NSCLC with brain metastases will receive AMG 193 PO

Treatment:

Drug: AMG 193