A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors

A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors

The main aims of this study are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or the recommended combination dose of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors, and to evaluate the preliminary anti-tumor activity of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).

Study Overview

• Status: Recruiting
• Conditions: MTAP-null Non-Small-Cell Lung Cancer; MTAP-null Solid Tumors
• Intervention / Treatment: Drug: AMG 193; Drug: IDE397

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Recruiting
      • The Queen Elizabeth Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Community Health Network MD Anderson Cancer Center - North
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • Astera Cancer Care
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health Upstate
  • Texas
    • Irving, Texas, United States, 75039
      • Recruiting
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Evidence of homozygous loss of MTAP (null) and/or MTAP deletion.

2. Presence of advanced/metastatic solid tumor not amenable to curative treatment

   1. Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists
   2. Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy.
3. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product
4. Disease measurable as defined by RECIST v1.1
5. Adequate organ function as defined in the protocol.
6. Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.

Exclusion Criteria

1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
2. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease.
3. Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
4. Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis)
5. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry.
6. Prior irradiation to > 25% of the bone marrow
7. Use of prescription medications that are known strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5 inducers or 5 half-lives, whichever is longer, prior to any dose of investigational medical product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Exploration of AMG 193 Combined With IDE397; Participants will receive escalating doses of AMG 193 and IDE397 administered orally (PO) in cycles of 21 days.	Drug: AMG 193; Administered PO; Drug: IDE397; Administered PO
Experimental: Part 2: Dose Expansion of AMG 193 Combined With IDE397; AMG 193 and IDE397 will be administered PO in cycles of 21 days.	Drug: AMG 193; Administered PO; Drug: IDE397; Administered PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)		Day 1 up to Day 21
Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events	Day 1 up to approximately 2.5 years
Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)		Day 1 up to approximately 2.5 years
Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1		Day 1 up to approximately 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Part 1 and 2: Cmax of IDE397		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Part 1 and 2: Tmax of IDE397		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Parts 1 and 2: AUC After Single Dose of IDE397		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Parts 1 and 2: AUC After Multiple Doses of IDE397		Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Parts 1: Overall Response per RECIST 1.1		Day 1 up to end-of-study (EOS) (approximately 2.5 years)
Parts 1 and 2: Disease Control Rate		Day 1 up to EOS (approximately 2.5 years)
Parts 1 and 2: Time to Response (TTR)		Day 1 up to EOS (approximately 2.5 years)
Parts 1 and 2: Duration of Response (DOR)		Day 1 up to EOS (approximately 2.5 years)
Parts 1 and 2: Duration of Stable Disease		Day 1 up to EOT (approximately 6 months)
Parts 1 and 2: Progression-free Survival (PFS)		Day 1 up to EOS (approximately 2.5 years)
Parts 1 and 2: Overall Survival (OS)		Day 1 up to EOS (approximately 2.5 years)
Part 2: Number of Participants Experiencing TEAEs	Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events	Day 1 up to approximately 2.5 years
Part 2: Number of Participants Experiencing SAEs		Day 1 up to approximately 2.5 years
Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood		Baseline (Day 1) to EOT plus 30 days (approximately 7 months)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 27, 2025
• Study Completion (Estimated): July 20, 2026

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Oncology; AMG 193; IDE397
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 20220127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No