Phase 1 First-In-Human Study to Explore AMG 305
Study Details
Study Description
Brief Summary
The primary objective of this study is to:
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Evaluate the safety and tolerability of AMG 305 in adult participants
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Determine the optimal biologically active dose (OBD), at or below the maximum tolerated dose (MTD) with MTD 1 as the maximum tolerated starting dose and MTD 2 as the maximum tolerated target dose
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Determine the recommended phase 2 dose (RP2D)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A: Dose Exploration Participants will receive escalating doses of AMG 305. |
Drug: AMG 305
AMG 305 will be administered as a short-term intravenous (IV) infusion (approximately 60 minutes).
|
| Experimental: Part B: Dose Expansion Participants with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer, and other solid tumors will receive the RP2D identified in Part A. |
Drug: AMG 305
AMG 305 will be administered as a short-term intravenous (IV) infusion (approximately 60 minutes).
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) [Day 1 to Day 28]
- Percentage of Participants who Experience Treatment-Emergent Adverse Events (TEAEs) [Up to a maximum of 2 years]
Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests, as assessed by the investigator, will also be reported as TEAEs.
- Percentage of Participants who Experience Treatment-Related Adverse Events [Up to a maximum of 2 years]
Secondary Outcome Measures
- Maximum Serum Concentration (Cmax) of AMG 305 [Up to a maximum of 2 years]
- Minimum Serum Concentration (Cmin) of AMG 305 [Up to a maximum of 2 years]
- Area Under the Concentration-Time Curve (AUC) of AMG 305 [Up to a maximum of 2 years]
- Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [Up to a maximum of 2 years]
ORR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), Clinical Benefit Rate (defined as BOR of CR, PR, or stable disease [SD] with duration of 24 weeks or longer) based on RECIST v1.1.
- ORR based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST) [Up to a maximum of 2 years]
ORR is defined as immune best overall response (iBOR) of immune complete response (iCR) or immune partial response (iPR), Clinical Benefit Rate (defined as iBOR of iCR, iPR, or immune stable disease [iSD] with duration of 24 weeks or longer) based on iRECIST.
- Duration of Response (DOR) [Up to a maximum of 2 years]
DOR is defined as the time from the first documentation of objective response until the first documentation of disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST.
- Time to Progression [Up to a maximum of 2 years]
Time to progression is defined as the time rom first AMG 305 dose until the first documentation of radiological disease progression by RECIST v1.1 and iRECIST.
- Progression-Free Survival (PFS) [Up to a maximum of 2 years]
PFS is defined as the time from first AMG 305 dose until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST.
- Overall Survival (OS) at 1 Year [1 year]
- OS at 2 Years [2 years]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
Pre-screening:
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Participant has provided informed consent prior to initiation of any pre screening study specific activities/procedures.
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Participants with histologically or cytologically documented solid tumor diseases expressing cadherin-3 and mesothelin (by mRNA in the Cancer Genome Atlas Program [TCGA] database), including CRC, NSCLC, mesothelioma, pancreatic cancer, gastric cancer, head and neck cancer, cervical carcinoma, uterine carcinoma, and breast cancer
Clinical study:
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Participant has provided inform consent to the main study prior to initiation of any study specific activities/procedures
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Male or female participants age ≥ 18 years
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
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Participants with histologically or cytologically documented solid tumor diseases, including CRC, NSCLC, mesothelioma, pancreatic cancer, GC, head and neck cancer, cervical carcinoma, uterine carcinoma, and breast cancer. Participants should have exhausted available standard of care (SOC) systemic therapy or should not be candidates for such available therapy
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For dose expansion cohorts: participants with at least 1 measurable lesion ≥10 mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study
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Life expectancy > 3 months
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Adequate organ function
Key Exclusion Criteria:
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Untreated central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
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History of other malignancy within the past 2 years
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Ongoing or active infection
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Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
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Known interstitial lung disease
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Positive test for human immunodeficiency virus (HIV)
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Positive hepatitis B surface antigen or positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
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Anticancer therapies including chemotherapy or molecularly targeted treatments or tyrosine kinase inhibitors (TKI) within 4 weeks or 5 half lives (whichever is longer) of administration of a first dose of study treatment; immunotherapies/monoclonal antibodies within 3 weeks of administration of a first dose of study treatment.
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Has had a major surgery within 4 weeks of administration of a first dose of study treatment
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Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study (eg, ulcerative colitis, Crohn's disease)
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Live and/or live-attenuated vaccines received within 28 days prior to the first dose of AMG 305
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Currently receiving treatment in another investigational device or drug study
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Female participants of childbearing potential or male participants unwilling to use protocol specified method of contraception
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Females who are pregnant, breastfeeding or who plan to breastfeed or become pregnant while on study
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History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20220073