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

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Anvumetostat in Combination With Carboplatin, Pemetrexed and Pembrolizumab; With Carboplatin, Paclitaxel and Pembrolizumab; or With Pembrolizumab in Subjects With Advanced Non-small Cell Lung Cancer (NSCLC) With Homozygous MTAP-deletion (Subprotocol A)

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

JPRN

Registry ID

JPRN-jRCT2051240116

Enrollment

500

Registered

2024-08-28

Start date

2024-09-17

Completion date

Unknown

Last updated

2026-09-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-small Cell Lung Cancer

Interventions

- Experimental: Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A Participants with MTAP-deleted NSCLC will receive a regimen of Anvumetostat orally (PO) and carboplatin, paclitaxel, and pembr

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion 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 Anvumetostat 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 (Anvumetostat + carboplatin + paclitaxel + pembrolizumab): - Predominantly squamous histology. Arm B (Anvumetostat + carboplatin + pemetrexed + pembrolizumab): - Predominantly non-squamous histology. Arm C (Anvumetostat + pembrolizumab): - PD-L1 positive.

Exclusion criteria

Exclusion 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 Anvumetostat. 5. Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor. 6. Radiation therapy within 28 days of first dose. Subprotocol A 7. Autoimmune disease or immunodeficiency disease as defined in the protocol

Design outcomes

Primary

Measure	Time frame
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.	—

Measure

Time frame

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.

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Secondary

Measure	Time frame
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 Anvumetostat [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)] 8. Time to Maximum Plasma Concentration (tmax) of Anvumetostat [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)] 9. Area Under the Plasma Concentration-time Curve (AUC) of Anvumetostat [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]	—

Measure

Time frame

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 Anvumetostat [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)] 8. Time to Maximum Plasma Concentration (tmax) of Anvumetostat [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)] 9. Area Under the Plasma Concentration-time Curve (AUC) of Anvumetostat [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]

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Countries

Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, Italy, Japan, Netherlands, Poland, South Korea, Spain, Taiwan, Turkey, United States

Contacts

Public ContactContact Local

Amgen K.K.

clinicaltrials_japan@amgen.com+81-80-7217-8592

Outcome results

None listed

Source: JPRN (via WHO ICTRP) · Data processed: Sep 19, 2026