MTAP-deleted NSCLC
Conditions
Interventions
Experimental: Part 1: Dose Evaluation
Participants will be randomized to receive one of 2 active dose levels of Anvumetostat orally (PO) daily (QD) in 28 days cycles. Part 1 of the study will determin
Sponsors
Iizumi Sakura
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed metastatic or unresectable locally advanced MTAP-deleted (Homozygous deletion of MTAP) NSCLC 2. Participants will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease. 3. Either an archival tissue sample or an archival block must be available. 4. Life expectancy of greater than 3 months, in the opinion of the investigator. 5. Participants who have had brain metastases and have been appropriately treated with radiation therapy or surgery ending at least 14 days before study day 1 are eligible. 6. Participants with untreated asymptomatic brain metastases smaller or equal to 2 cm in size (per lesion if more than one) and not requiring corticosteroid treatment are eligible.
Exclusion criteria
Exclusion criteria: Disease Related 1. Tumors harboring the following mutations amenable to targeted therapies: epidermal growth factor receptor (EGFR), ALK receptor tyrosine kinase (ALK), ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), MET proto-oncogene (MET), B-Raf proto-oncogene (BRAF), RET proto-oncogene (RET), Human epidermal growth factor receptor 2 (HER2/ERBB2), KRAS proto-oncogene G12C (KRAS G12C). Other Medical Conditions 2. Major surgery within 28 days of study day 1. 3. Untreated symptomatic central nervous system (CNS) metastatic disease regardless of size or asymptomatic brain metastases greater than 2cm per lesion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Objective Response (OR) per RECIST 1.1 [Time Frame: Up to 35 months] 2. Objective response (OR) Measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) and Assessed per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1) [Time Frame: Up to 35 months] 3. Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to 35 months] 4. Number of Participants Experiencing Events of Interest (EOIs) [Time Frame: Up to 35 months] 5. Maximum Concentration (Cmax) of anvumetostat [Time Frame: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose] 6. Time to Cmax (Tmax) of anvumetostat [Time Frame: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose] 7. Area Under The Concentration-time Curve (AUC) of anvumetostat [Time Frame: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Disease Control (DC) by BICR [Time Frame: Up to 35 months] 2. Duration of Response (DOR) by BICR [Time Frame: Up to 35 months] 3. Time to Response (TTR) by BICR [Time Frame: Up to 35 months] 4. Progression-free Survival (PFS) by BICR [Time Frame: Up to 35 months] 5. OR by Investigator's Assessment [Time Frame: Up to 35 months] 6. DC by Investigator's Assessment [Time Frame: Up to 35 months] 7. DOR by Investigator's Assessment [Time Frame: Up to 35 months] 8. TTR by Investigator's Assessment [Time Frame: Up to 35 months] 9. PFS by Investigator's Assessment [Time Frame: Up to 35 months] 10. Overall Survival (OS) [Time Frame: Up to 35 months] 11. Number of Participants Experiencing TEAEs [Time Frame: Up to 35 months] 12. Cmax of anvumetostat [Time Frame: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose] 13. Tmax of anvumetostat [Time Frame: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose] 14. AUC of anvumetostat [Time Frame: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day15 pre-dose; Cycles 3-5: Day 1 pre-dose] 15. Change in Quality of life (QoL) per The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC QLQ)-C30 [Time Frame: Up to 12 months] 16. Change in QoL per Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) [Time Frame: Up to 12 months] 17. Change in QoL per European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) [Time Frame: Up to 12 months] 18. Overall Health Status per Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Time Frame: Up to 12 months] 19. Overall Health Status per The Functional Assessment of Cancer Therapy - General (FACT-G) [Time Frame: Up to 12 months] | — |
Countries
Australia, Brazil, Canada, China, Czechia, Hong Kong, Japan, Latvia, Netherlands, Portugal, Singapore, South Korea, Switzerland, Taiwan, Turkey, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed