A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)

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A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)

Study Purpose

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 efficacy of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid tumors.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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) (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.

- 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 Criteria:
- 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05094336
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Amgen
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	MD
Principal Investigator Affiliation	Amgen
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Austria, Belgium, Canada, China, France, Germany, Hong Kong, Japan, South Korea, Switzerland, Taiwan, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Advanced MTAP-null Solid Tumors
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration

Participants with MTAP-null solid tumors will receive escalating doses of AMG 193 to estimate the MTD and/or the RP2D.

Experimental: Part 1c, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort: MTAP-null NSCLC.

Experimental: Part 2a, Phase 1: AMG 193 Dose Exploration + Docetaxel

Participants with MTAP-null NSCLC will receive escalating doses of AMG 193 + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination.

Experimental: Part 2b, Phase 1: AMG 193 + Docetaxel Dose Expansion

Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of AMG 193 + docetaxel.

Experimental: Part 3: AMG 193 Phase 2

Participants with MTAP-null solid tumors will receive AMG 193.

Experimental: Part 1e, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null BTC.

Experimental: Part 1f, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null head and neck squamous cell carcinoma (HNSCC).

Experimental: Part 1g, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null pancreatic adenocarcinoma.

Experimental: Part 1h, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null or lost MTAP expression solid tumors (other than lymphoma or primary brain tumor).

Experimental: Part 1i, Phase 1: AMG 193 Dose Optimization

Participants will receive a randomized dose optimization evaluation of AMG 193.

Experimental: Part 1j, Phase 1: AMG 193 DSPS Substudy (US Sites Only)

Participants will receive doses of AMG 193 and comparator AMG 193 test tables at different times in a fasted state.

Experimental: Part 1k, Phase 1: AMG 193 Food Effect Substudy (US Sites Only)

Participants will receive AMG 193 once on a fasted state and once after eating a standardized high-fat, high calorie meal.

Experimental: Part 1l, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null esophageal/gastric cancer.

Experimental: Part 1m, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null glioma.

Interventions

Drug: - AMG 193

AMG 193: Orally via tablet

Drug: - Docetaxel

Docetaxel: Intravenous infusion

Drug: - Comparator AMG 193 Test Tablet

Comparator AMG 193 test tablet: Orally via tablet. Only participants in the DSPS group of the Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration, and Part 1j, Phase 1 arms will receive comparator AMG 193 test tablet.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

City of Hope National Medical Center, Duarte 5344147, California 5332921

Status

Recruiting

Address

City of Hope National Medical Center

Duarte 5344147, California 5332921, 91010

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