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

Primary Purpose

MTAP-null Non-Small-Cell Lung Cancer, MTAP-null Solid Tumors

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 193
IDE397
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for MTAP-null Non-Small-Cell Lung Cancer focused on measuring Oncology, AMG 193, IDE397

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Evidence of homozygous loss of MTAP (null) and/or MTAP deletion. Presence of advanced/metastatic solid tumor not amenable to curative treatment Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product Disease measurable as defined by RECIST v1.1 Adequate organ function as defined in the protocol. 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 Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease. Cardiovascular and pulmonary exclusion criteria as defined in the protocol. 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) History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry. Prior irradiation to > 25% of the bone marrow 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.

Sites / Locations

  • City of Hope National Medical CenterRecruiting
  • Community Health Network MD Anderson Cancer Center - NorthRecruiting
  • Prisma Health UpstateRecruiting
  • Next OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: Dose Exploration of AMG 193 Combined With IDE397

Part 2: Dose Expansion of AMG 193 Combined With IDE397

Arm Description

Participants will receive escalating doses of AMG 193 and IDE397 administered orally (PO) in cycles of 21 days.

AMG 193 and IDE397 will be administered PO in cycles of 21 days.

Outcomes

Primary Outcome Measures

Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
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
Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)
Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary Outcome Measures

Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193
Part 1 and 2: Cmax of IDE397
Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
Part 1 and 2: Tmax of IDE397
Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193
Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193
Parts 1 and 2: AUC After Single Dose of IDE397
Parts 1 and 2: AUC After Multiple Doses of IDE397
Parts 1: Overall Response per RECIST 1.1
Parts 1 and 2: Disease Control Rate
Parts 1 and 2: Time to Response (TTR)
Parts 1 and 2: Duration of Response (DOR)
Parts 1 and 2: Duration of Stable Disease
Parts 1 and 2: Progression-free Survival (PFS)
Parts 1 and 2: Overall Survival (OS)
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
Part 2: Number of Participants Experiencing SAEs
Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood

Full Information

First Posted
July 19, 2023
Last Updated
September 20, 2023
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT05975073
Brief Title
A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
October 10, 2025 (Anticipated)
Study Completion Date
April 10, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MTAP-null Non-Small-Cell Lung Cancer, MTAP-null Solid Tumors
Keywords
Oncology, AMG 193, IDE397

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
184 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose Exploration of AMG 193 Combined With IDE397
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of AMG 193 and IDE397 administered orally (PO) in cycles of 21 days.
Arm Title
Part 2: Dose Expansion of AMG 193 Combined With IDE397
Arm Type
Experimental
Arm Description
AMG 193 and IDE397 will be administered PO in cycles of 21 days.
Intervention Type
Drug
Intervention Name(s)
AMG 193
Intervention Description
Administered PO
Intervention Type
Drug
Intervention Name(s)
IDE397
Intervention Description
Administered PO
Primary Outcome Measure Information:
Title
Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time Frame
Day 1 up to Day 21
Title
Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Description
Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events
Time Frame
Day 1 up to approximately 2.5 years
Title
Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)
Time Frame
Day 1 up to approximately 2.5 years
Title
Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame
Day 1 up to approximately 2.5 years
Secondary Outcome Measure Information:
Title
Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Part 1 and 2: Cmax of IDE397
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Part 1 and 2: Tmax of IDE397
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Parts 1 and 2: AUC After Single Dose of IDE397
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Parts 1 and 2: AUC After Multiple Doses of IDE397
Time Frame
Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
Title
Parts 1: Overall Response per RECIST 1.1
Time Frame
Day 1 up to end-of-study (EOS) (approximately 2.5 years)
Title
Parts 1 and 2: Disease Control Rate
Time Frame
Day 1 up to EOS (approximately 2.5 years)
Title
Parts 1 and 2: Time to Response (TTR)
Time Frame
Day 1 up to EOS (approximately 2.5 years)
Title
Parts 1 and 2: Duration of Response (DOR)
Time Frame
Day 1 up to EOS (approximately 2.5 years)
Title
Parts 1 and 2: Duration of Stable Disease
Time Frame
Day 1 up to EOT (approximately 6 months)
Title
Parts 1 and 2: Progression-free Survival (PFS)
Time Frame
Day 1 up to EOS (approximately 2.5 years)
Title
Parts 1 and 2: Overall Survival (OS)
Time Frame
Day 1 up to EOS (approximately 2.5 years)
Title
Part 2: Number of Participants Experiencing TEAEs
Description
Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events
Time Frame
Day 1 up to approximately 2.5 years
Title
Part 2: Number of Participants Experiencing SAEs
Time Frame
Day 1 up to approximately 2.5 years
Title
Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood
Time Frame
Baseline (Day 1) to EOT plus 30 days (approximately 7 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Evidence of homozygous loss of MTAP (null) and/or MTAP deletion. Presence of advanced/metastatic solid tumor not amenable to curative treatment Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product Disease measurable as defined by RECIST v1.1 Adequate organ function as defined in the protocol. 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 Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease. Cardiovascular and pulmonary exclusion criteria as defined in the protocol. 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) History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry. Prior irradiation to > 25% of the bone marrow 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amgen Call Center
Phone
866-572-6436
Email
medinfo@amgen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Community Health Network MD Anderson Cancer Center - North
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46250
Country
United States
Individual Site Status
Recruiting
Facility Name
Prisma Health Upstate
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Recruiting
Facility Name
Next Oncology
City
Irving
State/Province
Texas
ZIP/Postal Code
75039
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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