Cancer
Conditions
Keywords
Cancer, Carcinoma, Tumor, Solid tumor, Metastatic, Melanoma
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.
Interventions
DRUGAMP-224
Escalating doses of AMP-224
Sponsors
GlaxoSmithKline
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. |
| 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. |
Secondary
| Measure | 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. |
Countries
United States
Outcome results
None listed