Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors.

Study Overview
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Brief Summary
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The primary objective of this study is to: Evaluate the safety and tolerability of AMG 305 in adult participants 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 Determine the recommended phase 2 dose (RP2D)

Official Title
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Phase 1 First-In-Human Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AMG 305


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Pre-screening: Participant has provided informed consent prior to initiation of any pre screening study specific activities/procedures. 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: Participant has provided inform consent to the main study prior to initiation of any study specific activities/procedures Male or female participants age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 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 must have exhausted available standard of care (SOC) systemic therapy or must not be candidates for such available therapy 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 Life expectancy > 3 months Adequate organ function Key Exclusion Criteria: Untreated central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression History of other malignancy within the past 2 years Ongoing or active infection Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Known interstitial lung disease Positive test for human immunodeficiency virus (HIV) Positive hepatitis B surface antigen or positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR) Anticancer therapies including radiotherapy (with the exception of palliative radiation) 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. Has had a major surgery within 4 weeks of administration of a first dose of study treatment Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study (eg, ulcerative colitis, Crohn's disease) Live and/or live-attenuated vaccines received within 28 days (or longer, if required locally) prior to the first dose of AMG 305 Currently receiving treatment in another investigational device or drug study Female participants of childbearing potential or male participants unwilling to use protocol specified method of contraception Females who are pregnant, breastfeeding or who plan to breastfeed or become pregnant while on study 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Dose Exploration<br>Participants will receive escalating doses of AMG 305. | Drug: AMG 305<br>* Short-term intravenous (IV) infusion<br>|
| Experimental: Part B: Dose Expansion<br>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<br>* Short-term intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) |  | Day 1 to Day 28 | 
| Percentage of Participants who Experience Treatment-Emergent Adverse Events (TEAEs) | 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. | Up to a maximum of 2 years | 
| Percentage of Participants who Experience Treatment-Related Adverse Events |  | Up to a maximum of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Up to a maximum of 2 years | 
| ORR based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST) | 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. | Up to a maximum of 2 years | 
| Duration of Response (DOR) | 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. | Up to a maximum of 2 years | 
| Time to Progression | 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. | Up to a maximum of 2 years | 
| Progression-Free Survival (PFS) | 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. | Up to a maximum of 2 years | 
| Overall Survival (OS) at 1 Year |  | 1 year | 
| OS at 2 Years |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Pharmacokinetics