Brief Summary
The primary objective of Parts 1 and 2 of this study is to evaluate the safety, tolerability, and to determine the maximum tolerated dosethe amount of medication taken (MTD) or recommended phase 2 dose (RP2D) of AMG 193 alone and in combination with docetaxel in adult participants with metastatic or locally advancedat a late stage, far along methylthioadenosine phosphorylase (MTAP)-null solid tumors.
The primary objective of Part 3 of this study is to evaluate the efficacy of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid tumors.
Intervention / Treatment
- Drug: AMG 193
- Drug: Docetaxel
- Drug: Comparator AMG 193 Test Tablet
Inclusion Criteria:
- Participant has provided informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment./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 tissuea group of cells that work together to perform a function or bloodthe red bodily fluid that transports oxygen and other nutrients around the body (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
- Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence and/or radiation.
- 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). Note: except participants enrolling to Part 1m.
Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer 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 biopsyremoval of a section of tissue to analyse for cancer cells.
- 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.
- 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
- Subject able and willing to fast for ≥ 6 hours
Specific Inclusion Criteria for subjects with glioma (Part 1m only)
-Disease measurable as defined per Modified Response Assessment in Neuro-Oncology Criteria 2.0 (mRANO 2.0).