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RecruitingLast updated: 20 October 2025

MTAP: This study will evaluate the safety, tolerability and effectiveness of targeted therapy (AMG 193) is when given alone and in combination with chemotherapy in people with metastatic or locally advanced MTAP-null solid cancersA 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Multi-Cancer Multi-Cancer

Age

People18 - 100

Trial acronym

MTAP

Clinical summary

Summary

Please note, Epworth Jreissati Pancreatic Centre is currently recruiting patients with non-small cell lung cancer and biliary tract cancer.

This study has three parts.

The goal of Parts 1 and 2 of this study is to assess the safety and determine the highest safe dose (MTD) or recommended phase 2 dose (RP2D) of AMG 193 alone, and with docetaxel chemotherapy, in adults with advanced solid cancers lacking methylthioadenosine phosphorylase (MTAP).

Part 3 focuses on evaluating how effective AMG 193 is in treating adults with advanced solid tumours lacking MTAP.

Participants will recieve either AMG 193 on its own, or in combination with docetaxol. 

AMG 193 will be administered orally via tablet.

Docetaxel will be administered via intravenous infusion.

Conditions

This trial is treating patients with advanced MTAP-null solid tumours

Eligibility

Inclusion

  • 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).
  • 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). Note: except participants enrolling to Part 1m.

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.
  • 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)

Exclusion

  • Spinal cord compression or untreated brain metastases or leptomeningeal disease.
  • History of other malignancy within the past 2 years
  • Any evidence of current interstitial lung disease
  • Active infection
  • Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection.
  • History of arterial thrombosis
  • Myocardial infarction and/or symptomatic congestive heart failure.
  • Gastrointestinal tract disease
  • History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
  • History of solid organ transplant.
  • Diagnosis of Congenital Short QT Syndrome.
  • Major surgery
  • Anti-tumor therapy within 28 days of study day 1.
  • Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
  • Prior treatment with docetaxel (Part 2 only)
  • Prior irradiation to 25% of the bone marrow.
  • Therapeutic or palliative radiation therapy within 2 weeks of study day 1.
  • Live vaccine therapy within 4 weeks before study drug administration.
  • Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
  • Use of prescription medications that are known strong inducers of cytochrome P450 3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1
  • Unresolved toxicity from prior anti-cancer therapy
  • Currently receiving treatment in another investigational device or drug study.
  • Known positive test for Human Immunodeficiency Virus (HIV).
  • Positive hepatitis B surface antigen
  • positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
  • Female participants of childbearing potential unwilling to use protocol specified method of contraception

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body (localised).
  • Your cancer has not spread to other parts of the body, but it is not possible to perform surgery to remove it (unresectable).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.

Exclusion

  • You are currently being treated on a clinical trial.
  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Amgen

Scientific Title

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

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