AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06333951
• Other study ID #: 20230167
• Status: Recruiting
• Phase: Phase 1
• Start date: June 28, 2024
• Est. completion date: November 3, 2029

Study information

• Verified date: June 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor AMG 193 administered in combination with other therapies in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deleted thoracic tumors. The study also aims to determine the safety profile of AMG 193 administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted thoracic tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: November 3, 2029
• Est. primary completion date: November 4, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria

Subprotocol A, B, and C

• Age = 18 years (or = legal age within the country if it is older than 18 years).

• Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before AMG 193 dosing.

• Homozygous MTAP-deletion.

• Able to swallow and retain PO administered study treatment.

• Disease measurable as defined by RECIST v1.1.

Subprotocol A

• Histologically or cytologically confirmed diagnosis of NSCLC.

Arm A (AMG 193 + carboplatin + paclitaxel + pembrolizumab):

• Predominantly squamous histology.

Arm B (AMG 193 + carboplatin + pemetrexed + pembrolizumab):

• Predominantly non-squamous histology.

Arm C (AMG 193 + pembrolizumab):

• PD-L1 positive.

Subprotocol B

• Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation.

Subprotocol C

• Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases.

• Brain lesion meeting RANO-BM criteria for measurable disease.

Exclusion Criteria

Subprotocol A, B, and C

• 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 solid organ transplant.

• Major surgery within 28 days of first dose of AMG 193.

• Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.

• Radiation therapy within 28 days of first dose.

Related Conditions & MeSH terms

• Non-small Cell Lung Cancer
• Thoracic Neoplasms
• Thoracic Tumors

Intervention

Drug:
• AMG 193
Administered PO
• Carboplatin
Administered IV
• Paclitaxel
Administered IV
• Pembrolizumab
Administered IV
• Pemetrexed
Administered IV
• Sotorasib
Administered PO

Locations

Country	Name	City	State
United States	City of Hope (COH)	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Dose Limiting Toxicities (DLT)		Up to approximately 21 days
Primary	Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)	TEAEs are any event that occurred after the participant received study treatment. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. A serious TEAE is any untoward medical occurrence in a clinical study participant after first dose irrespective of a causal relationship with the study treatment(s) that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.	Up to approximately 3 years
Primary	Number of Participants Experiencing Serious Adverse Events (SAE)	An SAE is defined as any AE that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.	Up to approximately 3 years
Secondary	Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)		Up to approximately 3 years
Secondary	Disease Control (DC) per RECIST v1.1		Up to approximately 3 years
Secondary	Duration of Response (DOR) per RECIST v1.1		Up to approximately 3 years
Secondary	Time to Response (TTR) per RECIST v1.1		Up to approximately 3 years
Secondary	Overall Survival (OS) per RECIST v1.1		Up to approximately 3 years
Secondary	Progression-free Survival (PFS) per RECIST v1.1		Up to approximately 3 years
Secondary	Maximum Plasma Concentration (Cmax) of AMG 193		Up to Day 1 of Cycle 5 (one cycle = 21 days)
Secondary	Time to Maximum Plasma Concentration (tmax) of AMG 193		Up to Day 1 of Cycle 5 (one cycle = 21 days)
Secondary	Area Under the Plasma Concentration-time Curve (AUC) of AMG 193		Up to Day 1 of Cycle 5 (one cycle = 21 days)
Secondary	Intracranial objective response (IOR) per Response Assessment in Neuro Oncology Brain Metastases (RANO-BM )		Up to approximately 3 years
Secondary	Intracranial Disease Control (IDC) per RANO-BM		Up to approximately 3 years
Secondary	Intracranial Duration of Response (IDOR) per RANO-BM		Up to approximately 3 years
Secondary	Time to Intracranial Radiation Therapy per RANO-BM		Up to approximately 3 years

External Links

•   AmgenTrials clinical trials website