Clinical trial NCT05975073: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: MTAP-null Non-Small-Cell Lung Cancer
MTAP-null Solid Tumors
Keywords: Oncology
AMG 193
IDE397
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-08-03
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to Day 21
measure: Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to approximately 2.5 years
measure: Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Day 1 up to approximately 2.5 years
measure: Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Day 1 up to approximately 2.5 years
Secondary outcomes:
measure: Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Part 1 and 2: Cmax of IDE397
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Part 1 and 2: Tmax of IDE397
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Parts 1 and 2: AUC After Single Dose of IDE397
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Parts 1 and 2: AUC After Multiple Doses of IDE397
timeFrame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
measure: Parts 1: Overall Response per RECIST 1.1
timeFrame: Day 1 up to end-of-study (EOS) (approximately 2.5 years)
measure: Parts 1 and 2: Disease Control Rate
timeFrame: Day 1 up to EOS (approximately 2.5 years)
measure: Parts 1 and 2: Time to Response (TTR)
timeFrame: Day 1 up to EOS (approximately 2.5 years)
measure: Parts 1 and 2: Duration of Response (DOR)
timeFrame: Day 1 up to EOS (approximately 2.5 years)
measure: Parts 1 and 2: Duration of Stable Disease
timeFrame: Day 1 up to EOT (approximately 6 months)
measure: Parts 1 and 2: Progression-free Survival (PFS)
timeFrame: Day 1 up to EOS (approximately 2.5 years)
measure: Parts 1 and 2: Overall Survival (OS)
timeFrame: Day 1 up to EOS (approximately 2.5 years)
measure: Part 2: Number of Participants Experiencing TEAEs
timeFrame: Day 1 up to approximately 2.5 years
measure: Part 2: Number of Participants Experiencing SAEs
timeFrame: Day 1 up to approximately 2.5 years
measure: Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood
timeFrame: Baseline (Day 1) to EOT plus 30 days (approximately 7 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Indianapolis
country: United States
facility: Community Health Network MD Anderson Cancer Center - North
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Paul
country: United States
facility: Health Partners Cancer Center at Regions Hospital
state: Minnesota
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: New York
country: United States
facility: New York University Grossman School of Medicine and New York University Langone Hospitals
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: Next Oncology
state: Texas
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: