AMG 193, Methylthioadenosine (MTA) Cooperative Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, Alone and in Combination With Docetaxel in Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors
The primary objective of Parts 1 and 2 of this study is to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG 193 alone and in combination with docetaxel in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.
The primary objective of Part 3 of this study is to evaluate the objective response rate (ORR) of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid tumors.
A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors
Participant has provided informed consent/assent before initiation of any study specific activities/procedures.
Age ≥ 18 years.
Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null) (Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP) (null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
Able to swallow and retain orally (PO) administered study treatment and willing to record daily adherence to investigational product.
Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Adequate hematopoietic function per local laboratory
Adequate renal function per local laboratory
Adequate glucose control per local laboratory (Part 1 only)
Adequate liver function per local laboratory
Adequate coagulation parameters
Adequate pulmonary function
Adequate cardiac function
Minimum life expectancy of 12 weeks as per investigator judgement.
A total of 25 slides of archived tumor tissue (formalin-fixed, paraffin-embedded [FFPE] sample collected within 5 years) or an archival block must be available.
For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo tumor biopsy.
For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment (archival sample acceptable if obtained with 6 months of enrollment and subject has not received any other treatment since sample was obtained) and while on treatment.
Part 1i: Enrollment criteria for Part 1i are to match the criteria of the expansion arm from which the indication was selected.
For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sites only).
Food Effect Substudy (Part 1k): Specific Inclusion Criteria
Subject able and willing to eat a standardized high-fat, high-caloric meal