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

• Status: Not yet recruiting
• Trial end date: 2024-11-13
• Target enrollment: 0
• Participant gender: All

Summary

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 non-small cell lung cancer (NSCLC), after prior treatment with chemotherapy and/or a programmed death-1/ligand 1 (PD-1/L1) inhibitor.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amgen
• Treatments: Docetaxel

Criteria

Inclusion Criteria:

• 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) and/or methylthioadenosine phosphorylase (MTAP) (null) or lost MTAP expression in the tumor tissue.

• Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery 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).

• 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.

• Tumor tissue must be available.

Exclusion Criteria:

• Spinal cord compression or active brain metastases or leptomeningeal disease from non-brain tumors.

• Presence of primary brain cancer.

• Presence of hematological malignancy or lymphoma.

• History of other malignancy within the past 2 years.

• Evidence of lung disease.

• Active infection.

• History of arterial thrombosis.

• Myocardial infarction and/or symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia.

• Gastrointestinal tract disease.

• History of solid organ transplant.

• Diagnosis of Congenital Short QT Syndrome.

• Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.

• Prior irradiation to greater than 25% of the bone marrow.

• Unresolved toxicity from prior anti-cancer therapy.

• Currently receiving treatment in another investigational device or drug study.

• Known positive test for Human Immunodeficiency Virus.

• Evidence of hepatitis B or C infection.

• Female participants of childbearing potential with a positive pregnancy test.