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

Phase 1

Recruiting

• Conditions: Thoracic Tumors; Non-small Cell Lung Cancer
• Interventions: Drug: AMG 193; Drug: Carboplatin; Drug: Sotorasib; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: Pemetrexed

• Registration Number: NCT06333951
• Lead Sponsor: Amgen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-21
• Study First Submitted QC: 2024-03-21
• Study First Posted: 2024-03-27
• Study Start: 2024-09-17
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-21
• Last Update Posted: 2024-12-27
• Primary Completion: 2028-10-27
• Study Completion: 2031-10-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Subprotocol C: NSCLC With Brain Metastases	AMG 193	Participants with MTAP-deleted NSCLC with brain metastases will receive AMG 193 PO
Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A	AMG 193	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)
Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A	Carboplatin	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)
Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A	Paclitaxel	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)
Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A	Pembrolizumab	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)
Subprotocol A: NSCLC Arm B	AMG 193	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 PO and carboplatin, pemetrexed, and pembrolizumab IV
Subprotocol A: NSCLC Arm B	Carboplatin	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 PO and carboplatin, pemetrexed, and pembrolizumab IV
Subprotocol A: NSCLC Arm B	Pembrolizumab	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 PO and carboplatin, pemetrexed, and pembrolizumab IV
Subprotocol A: NSCLC Arm B	Pemetrexed	Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 PO and carboplatin, pemetrexed, and pembrolizumab IV
Subprotocol A: NSCLC Arm C	AMG 193	Participants with MTAP-deleted NSCLC will receive a combination of AMG 193 PO and pembrolizumab IV
Subprotocol A: NSCLC Arm C	Pembrolizumab	Participants with MTAP-deleted NSCLC will receive a combination of AMG 193 PO and pembrolizumab IV
Subprotocol B: NSCLC With KRasG12C Mutation	AMG 193	Participants with MTAP-deleted NSCLC and KRasG12C mutation will receive a combination of AMG 193 and sotorasib PO
Subprotocol B: NSCLC With KRasG12C Mutation	Sotorasib	Participants with MTAP-deleted NSCLC and KRasG12C mutation will receive a combination of AMG 193 and sotorasib PO

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
Intracranial Disease Control (IDC) per RANO-BM	Up to approximately 3 years
Progression-free Survival (PFS) per RECIST v1.1	Up to approximately 3 years
Time to Response (TTR) per RECIST v1.1	Up to approximately 3 years
Duration of Response (DOR) per RECIST v1.1	Up to approximately 3 years
Intracranial objective response (IOR) per Response Assessment in Neuro Oncology Brain Metastases (RANO-BM )	Up to approximately 3 years
Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	Up to approximately 3 years
Overall Survival (OS) per RECIST v1.1	Up to approximately 3 years
Disease Control (DC) per RECIST v1.1	Up to approximately 3 years
Time to Maximum Plasma Concentration (tmax) of AMG 193	Up to Day 1 of Cycle 5 (one cycle = 21 days)
Time to Intracranial Radiation Therapy per RANO-BM	Up to approximately 3 years
Maximum Plasma Concentration (Cmax) of AMG 193	Up to Day 1 of Cycle 5 (one cycle = 21 days)
Area Under the Plasma Concentration-time Curve (AUC) of AMG 193	Up to Day 1 of Cycle 5 (one cycle = 21 days)
Intracranial Duration of Response (IDOR) per RANO-BM	Up to approximately 3 years

Trial Locations

Locations (31)

University of California Irvine; 🇺🇸 Orange, California, United States

Comprehensive Blood and Cancer Center; 🇺🇸 Bakersfield, California, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Translational Research in Oncology US Inc, Trio Central Pharmacy; 🇺🇸 Los Angeles, California, United States

University of California Los Angeles; 🇺🇸 Santa Monica, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Denver, Colorado, United States

Eastern Connecticut Hematology and Oncology Associates; 🇺🇸 Norwich, Connecticut, United States

HealthPartners Institute; 🇺🇸 Saint Paul, Minnesota, United States

Saint Lukes Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

New York University Grossman School of Medicine; 🇺🇸 New York, New York, United States

Perlmutter Cancer Center at New York University Langone Hospital----Long Island; 🇺🇸 New York, New York, United States

Hightower Clinical; 🇺🇸 Oklahoma City, Oklahoma, United States

University of Tennessee Medical Center Knoxville; 🇺🇸 Knoxville, Tennessee, United States

Baylor Charles A Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Texas Oncology - Dallas Fort Worth; 🇺🇸 Dallas, Texas, United States

US Oncology Research Investigational Products Center; 🇺🇸 Dallas, Texas, United States

Oncology Consultants Cancer Center; 🇺🇸 Houston, Texas, United States

Texas Oncology Northeast Texas; 🇺🇸 Tyler, Texas, United States

Virginia Cancer Specialists PC; 🇺🇸 Fairfax, Virginia, United States

Northwest Medical Specialties, PLLC; 🇺🇸 Tacoma, Washington, United States

Orange Health Service; 🇦🇺 Orange, New South Wales, Australia

The Queen Elizabeth Hospital; 🇦🇺 Woodville South, South Australia, Australia

Prince of Wales Hospital / CUHK; 🇭🇰 Shatin, New Territories, Hong Kong

Aichi Cancer Center; 🇯🇵 Nagoya-shi, Aichi, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa-shi, Chiba, Japan

Shizuoka Cancer Center; 🇯🇵 Sunto-gun, Shizuoka, Japan

Wakayama Medical University Hospital; 🇯🇵 Wakayama-shi, Wakayama, Japan

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan