Trial summary: This study aims to assess the safety and tolerability of AMG 193 in adults with metastatic or locally advanced MTAP-null solid tumours. Parts 1 and 2 will determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 193, both alone and in combination with docetaxel. Part 3 will evaluate the effectiveness of AMG 193 in advanced MTAP-null solid tumours.
Status: OPEN - Recruiting
Trial identifier: NCT05094336
Sponsor: Amgen
Phase: I
Diagnosis: Locally advanced (Stage III) unresectable or metastatic (Stage IV) pancreatic ductal adenocarcinoma
Line of therapy: Second-line +
Treatment: PRMT5 inhibitor AMG193 (oral) monotherapy
  • Key inclusion criteria
    1. Participant has provided informed consent/assent before initiation of any study specific activities/procedures.
    2. Age ≥ 18 years.
    3. 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).
    4. Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.
    5. Able to swallow and retain orally (PO) administered study treatment and willing to record daily adherence to investigational product.
    6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
    7. Adequate hematopoietic function per local laboratory.
    8. Adequate renal function per local laboratory.
    9. Adequate glucose control per local laboratory (Part 1 only).
    10. Adequate liver function per local laboratory.
    11. Adequate coagulation parameters.
    12. Adequate pulmonary function.
    13. Adequate cardiac function.
    14. Minimum life expectancy of 12 weeks as per investigator judgement.
    15. 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.
    16. For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo tumor biopsy.
    17. For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment (archival sample acceptable if obtained within 6 months of enrollment and subject has not received any other treatment since sample was obtained) and while on treatment.
  • Key exclusion criteria
    1. Spinal cord compression or untreated brain metastases or leptomeningeal disease.
    2. History of other malignancy within the past 2 years.
    3. Any evidence of current interstitial lung disease.
    4. Active infection.
    5. Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection.
    6. History of arterial thrombosis.
    7. Myocardial infarction and/or symptomatic congestive heart failure.
    8. Gastrointestinal tract disease.
    9. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess.
    10. History of solid organ transplant.
    11. Diagnosis of Congenital Short QT Syndrome.
    12. Major surgery.
    13. Anti-tumor therapy within 28 days of study day 1, unless anti-tumor therapy is a therapy with 5 times the half-life being shorter than 28 days.
    14. Prior treatment with a methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
    15. Prior treatment with docetaxel (Part 2 only).
    16. Prior irradiation to 25% of the bone marrow.
    17. Therapeutic or palliative radiation therapy within 2 weeks of study day 1.
    18. Live vaccine therapy within 4 weeks before study drug administration.
    19. Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
    20. 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.
    21. Unresolved toxicity from prior anti-cancer therapy.
    22. Currently receiving treatment in another investigational device or drug study.
    23. Known positive test for Human Immunodeficiency Virus (HIV).
    24. Positive hepatitis B surface antigen.
    25. Positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR).
    26. Female participants of childbearing potential unwilling to use protocol-specified method of contraception.

AMG193 20210023

Locations: Epworth Richmond, Epworth Freemasons (East Melbourne), Epworth Eastern (Box Hill).

Epworth PI: A/Prof Sumitra Ananda

Jreissati Pancreatic Centre at Epworth 

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