A Study of AMG 193 in Subjects With Advanced MTAP-null Solid Tumors

Amgen

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced MTAP-null Solid Tumors

Treatments: Drug: Comparator AMG 193 Test Tablet; Drug: Docetaxel; Drug: AMG 193

Study type: Interventional

Funder types: Industry

Identifiers

NCT05094336

20210023

2023-504363-17 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 649 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.
• 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 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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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649 participants in 14 patient groups

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

Experimental group

Description:

Participants with MTAP-null solid tumors will receive escalating doses of AMG 193 to estimate the MTD and/or the RP2D. A group of these participants in the United States (US) will have the option to take part in a Drug Substance Particle Size (DSPS) assessment. These participants will receive AMG 193 at a selected dose and a dose of a comparator AMG 193 table(s).

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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.

Treatment:

Drug: AMG 193

Drug: Docetaxel

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

Drug: Docetaxel

Part 3: AMG 193 Phase 2

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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).

Treatment:

Drug: AMG 193

Part 1i, Phase 1: AMG 193 Dose Optimization

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

Drug: Comparator AMG 193 Test Tablet

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193

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

Experimental group

Description:

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

Treatment:

Drug: AMG 193