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

• ClinicalTrials.gov Identifier: NCT01352884
• Recruitment Status: Completed
• First Posted: May 12, 2011
• Last Update Posted: September 5, 2016
• Sponsor: MedImmune LLC
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): MedImmune LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: AMP-224	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: March 2011
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Stage 1; 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; Escalating doses of AMP-224
Experimental: Stage 2; 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; 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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events. [ Time Frame: 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. ]
2. Number of participants with dose-limiting toxicities. [ Time Frame: 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. ]
3. Number of participants with changes in laboratory values, vital signs, physical exam, and electrocardiogram. [ Time Frame: 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. ]
4. Determine Maximum Tolerated Dose based on the occurrence of dose-limiting toxicities. [ Time Frame: From start of study drug administration through Day 28 of Cycle 1. ]
5. Determine Recommended Phase 2 Dose following analysis of adverse events, pharmacokinetics and changes in laboratory evaluations. [ Time Frame: From start of study drug administration until withdrawal; through Day 56 of final cycle. ]

Secondary Outcome Measures :

1. 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. [ Time Frame: From Day 0 pre-dose through Day 56 of final cycle. ]
2. Evaluate Overall Response Rate (ORR), including Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression-Free Survival (PFS). [ Time Frame: From Screening through 12 weeks following final cycle. ]
3. 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. [ Time Frame: From Screening until 12 weeks post-final cycle. ]
4. 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. [ Time Frame: Screening through 12 weeks post-final cycle. ]
5. Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry. [ Time Frame: Screening through 12 weeks post-final cycle. ]
6. Identification of peripheral patient selection and pharmacodynamic markers from blood samples that predict and/or correlate with response to treatment. [ Time Frame: Screening through 12 weeks post-final cycle. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Carolina BioOncology Institute

Huntersville, North Carolina, United States, 28078

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

MedImmune LLC

GlaxoSmithKline

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Borch TH, Donia M, Andersen MH, Svane IM. Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies. Drug Discov Today. 2015 Sep;20(9):1127-34. doi: 10.1016/j.drudis.2015.07.003. Epub 2015 Jul 17. Review.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT01352884
• Other Study ID Numbers: AMP-224-01
• First Posted: May 12, 2011
• Last Update Posted: September 5, 2016
• Last Verified: August 2016

Keywords provided by MedImmune LLC:

Cancer; Carcinoma; Tumor; Solid tumor; Metastatic; Melanoma