Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-224 in Patients With Advanced Cancer

Study Overview
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Brief Summary
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This is a Phase 1, open-label, multi-center, first time in human study of AMP-224 in adult patients with cancer that is not responding to standard therapy. This study will be conducted in two stages consisting of a Dose-Escalation stage and an Expansion Stage.

Conditions
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Cancer

Intervention / Treatment
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* Drug: AMP-224
* Drug: AMP-224


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to provide informed consent In Dose-Escalation: Must have solid tumor malignancy or cutaneous T-cell lymphoma that has relapsed and is refractory to standard therapy, or for which no standard therapy exists In Expansion Phase: Must have melanoma or ovarian cancer that is histologically or cytologically confirmed Ovarian cancer patients must have recurrent of persistent non-mucinous disease, and must not have received more than 2 prior chemotherapeutic regimens Melanoma patients must have recurrent or persistent non-ocular AJCC Stage IIIC or IV disease that is surgically incurable and unresectable Melanoma patients with documented BRAF mutation that is known to be responsive to BRAF inhibitors must have failed or be intolerant to such inhibitors Must have measurable disease Must be able to provide access to archival (Dose-Escalation Phase) and/or fresh tumor tissue (Dose-Escalation and Expansion Phases) at Screening prior to study entry Must by at least 18 years old Must have adequate organ function Exclusion Criteria: Prior cancer therapies must have completed at least 14 days or 5 half-lives (whichever is longer) prior to first dose of AMP-224 Prior treatment with an anti-PD1 antibody therapy Known antibody response against prior antibody therapy or fusion protein therapeutics Major surgery within 4 weeks prior to first dose of AMP-224 Prior allogeneic or autologous bone marrow or organ transplantation Known and/or a history or evidence of autoimmune disease except vitiligo, resolved childhood asthma and stable hypothyroidism Received an immunomodulatory drug within 2 weeks of first dose of AMP-224 Active infections requiring antibiotics, physician monitoring, or recurrent fevers >100.4 degrees fahrenheit associated with a clinical diagnosis of active infection Patients with cirrhosis Clinically significant cardiac or electrocardiogram abnormalities History or evidence of HIV Active viral disease (except when the viral infection is associated with the malignancy) Regular use of illicit drugs or a recent history of substance abuse Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1<br>Stage 1 will identify the recommended Stage 2 dose using a dose-escalation process. Dose-escalation will continue until either a maximum tolerated dose is established, or a therapeutic dose is reached. | Drug: AMP-224<br>* Escalating doses of AMP-224<br>|
| Experimental: Stage 2<br>Stage 2 will further explore the safety, pharmacokinetics, and preliminary clinical activity of AMP-224 in at least one tumor type based on pharmacodynamic assessments and clinical activity emerging from the Dose-Escalation Phase. Tumor tissue and blood specimens will be evaluated for pharmacodynamic markers/activity at specified timepoints throughout the study. | Drug: AMP-224<br>* Stage 2 will further explore the safety, pharmacokinetics, and preliminary clinical activity of AMP-224 in at least one tumor type based on pharmacodynamic assessments and clinical activity emerging from the Dose-Escalation Phase. Tumor tissue and blood<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events. |  | From start of study drug administration until the date of first documented progression or date of death from any cause; through Day 56 of final cycle. | 
| Number of participants with dose-limiting toxicities. |  | From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle. | 
| Number of participants with changes in laboratory values, vital signs, physical exam, and electrocardiogram. |  | From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle. | 
| Determine Maximum Tolerated Dose based on the occurrence of dose-limiting toxicities. |  | From start of study drug administration through Day 28 of Cycle 1. | 
| Determine Recommended Phase 2 Dose following analysis of adverse events, pharmacokinetics and changes in laboratory evaluations. |  | From start of study drug administration until withdrawal; through Day 56 of final cycle. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate pharmacokinetics, including area under the plasma concentration versus time curve (AUC), peak plasma concentration (Cmax) and clearance of AMP-224 following single and repeat doses of AMP-224. |  | From Day 0 pre-dose through Day 56 of final cycle. | 
| Evaluate Overall Response Rate (ORR), including Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression-Free Survival (PFS). |  | From Screening through 12 weeks following final cycle. | 
| Characterization of the effects of AMP-224 on its receptor, PD-1, in peripheral T cells via flow cytometry and correlate with response to treatment. |  | From Screening until 12 weeks post-final cycle. | 
| Evaluation and correlation between response to treatment and expression of PD-1 on tumor infiltrating T cells or in available malignant pleural effusions via flow cytometry and/or immunohistochemistry. |  | Screening through 12 weeks post-final cycle. | 
| Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry. |  | Screening through 12 weeks post-final cycle. | 
| Identification of peripheral patient selection and pharmacodynamic markers from blood samples that predict and/or correlate with response to treatment. |  | Screening through 12 weeks post-final cycle. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Carcinoma, Tumor, Solid tumor, Metastatic, Melanoma