AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) AMG 193 in Combination With Carboplatin, Pemetrexed and Pembrolizumab; With Carboplatin, Paclitaxel and Pembrolizumab; or With Pembrolizumab in Subjects With Advanced NSCLC With Homozygous MTAP-deletion (Subprotocol A)

JRCT ID: jRCT2051240116

Registered date:28/08/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-small Cell Lung Cancer
• Date of first enrollment: 30/08/2024
• Target sample size: 500
• Countries of recruitment: United States,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A
Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)
Interventions:
Drug: AMG 193
Drug: Carboplatin
Drug: Paclitaxel
Drug: Pembrolizumab

- Experimental: Subprotocol A: NSCLC Arm B
Participants with MTAP-deleted NSCLC will receive a regimen of AMG 193 PO and carboplatin, pemetrexed, and pembrolizumab IV
Interventions:
Drug: AMG 193
Drug: Carboplatin
Drug: Pembrolizumab
Drug: Pemetrexed

- Experimental: Subprotocol A: NSCLC Arm C
Participants with MTAP-deleted NSCLC will receive a combination of AMG 193 PO and pembrolizumab IV
Interventions:
Drug: AMG 193
Drug: Pembrolizumab

Outcome(s)

Primary Outcome

1. Number of Participants Experiencing Dose Limiting Toxicities (DLT) [Time Frame: Up to approximately 21 days]
2. Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE) [Time Frame: 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.
3. Number of Participants Experiencing Serious Adverse Events (SAE) [Time Frame: 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.

Secondary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Subprotocol A
1. Age >= 18 years (or >= legal age within the country if it is older than 18 years).
2. 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.
3. Homozygous MTAP-deletion.
4. Able to swallow and retain PO administered study treatment.
5. 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.

Exclude criteria

Subprotocol A
1. Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
2. 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).
3. History of solid organ transplant.
4. Major surgery within 28 days of first dose of AMG 193.
5. Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
6. Radiation therapy within 28 days of first dose.

Related Information

• Primary Sponsor: Iizumi Sakura
• Secondary ID(s): NCT06333951