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

Cancer Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01352884
• Other study ID #: AMP-224-01
• Status: Completed
• Phase: Phase 1
• First received: May 6, 2011
• Last updated: September 2, 2016
• Start date: March 2011
• Est. completion date: January 2014

Study information

• Verified date: August 2016
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• AMP-224
Escalating doses of AMP-224
• 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

Locations

Country	Name	City	State
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
MedImmune LLC	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Primary	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.	Yes
Primary	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.	Yes
Primary	Determine Maximum Tolerated Dose based on the occurrence of dose-limiting toxicities.		From start of study drug administration through Day 28 of Cycle 1.	Yes
Primary	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.	Yes
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry.		Screening through 12 weeks post-final cycle.	No
Secondary	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.	No