Study of AMG 256 in Adult Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of AMG 256 in adult participants and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Official Title
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A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 256 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AMG 256


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has provided informed consent prior to initiation of any study specific activities/procedures. Age ≥ 18 years at the time of signing informed consent. Life expectancy of > 3 months, in the opinion of the investigator. Participant must have histologically or cytologically proven metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation for which: No standard therapy exists, or Standard therapy has failed, not available, or In the investigator's opinion, standard therapy does not result in meaningful clinical benefit. 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. Exclusion Criteria: Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal disease. History of other malignancy within the past 2 years, with the following Exceptions: Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated cervical carcinoma in situ without evidence of disease. Adequately treated breast ductal carcinoma in situ without evidence of disease. Prostatic intraepithelial neoplasia without evidence of prostate cancer. Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. History of solid organ transplantation. Major surgery within 28 days of study day 1. Live vaccine therapy within 4 weeks prior to study day 1. Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Active infection requiring oral or intravenous therapy. Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or cardiac arrhythmia requiring medication. History of severe allergic reactions or severe acute hypersensitivity reaction. Female participant is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 3 months after the last dose of AMG 256. Female participants of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 3 months after the last dose of AMG 256. Female participants of childbearing potential with a positive pregnancy test assessed within 48 hours prior to day 1 of treatment by a serum pregnancy test. Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 5 months after the last dose of AMG 256. Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 5 months after the last dose of AMG 256. Male participants unwilling to abstain from donating sperm during treatment and for an additional 5 months after the last dose of AMG 256. Participant has known sensitivity to any of the products or components to be administered during dosing. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge. History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participants 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Phase<br>Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose RP2D of AMG 256. | Drug: AMG 256<br>* AMG 256 administered as an intravenous (IV) infusion.<br>|
| Experimental: Dose Expansion Phase: Group 1<br>Participants will be administered with the MTD or RP2D of AMG 256 identified in the dose escalation part of the study. | Drug: AMG 256<br>* AMG 256 administered as an intravenous (IV) infusion.<br>|
| Experimental: Dose Expansion Phase: Group 2<br>Participants will be administered with the MTD or RP2D of AMG 256 identified in the dose escalation part of the study. | Drug: AMG 256<br>* AMG 256 administered as an intravenous (IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) |  | 28 days | 
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) |  | Up to 2.5 Years | 
| Number of Participants with Treatment-Related Adverse Events |  | Up to 2.5 Years | 
| Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurement |  | Up to 2 Years | 
| Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests |  | Up to 2 Years | 
| Maximum Tolerated Dose (MTD) of AMG 256 |  | 28 days | 
| Recommended Phase 2 Dose (RP2D) of AMG 256 |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of AMG 256 |  | Up to 2.5 Years | 
| Time to Achieve Cmax (Tmax) of AMG 256 |  | Up to 2.5 Years | 
| Area Under the Plasma Concentration-time Curve (AUC) of AMG 256 |  | Up to 2.5 Years | 
| Objective Response (OR) |  | Up to 2.5 Years | 
| Duration of Response (DOR) |  | Up to 2.5 Years | 
| Progression-Free Survival (PFS) |  | Up to 1 Year | 
| Disease Control Rate (DCR) |  | Up to 2.5 Years | 
| Duration of Stable Disease |  | Up to 2.5 Years | 
| Overall Survival (OS) |  | Up to 2 Years | 
| Number of Participants with anti-AMG 256 Antibodies |  | Up to 2.5 Years |