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Brief Title: Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma
Official Title: Phase 1 Safety Run-In and Phase 2 Randomized Clinical Trial of Anetumab Ravtansine and Pembrolizumab (MK-3475) Compared to Pembrolizumab Alone for Mesothelin-Positive Malignant Pleural Mesothelioma
Study ID: NCT03126630
Brief Summary: This phase I/II trial studies the side effects and how well pembrolizumab with or without anetumab ravtansine works in treating patients with mesothelin-positive pleural mesothelioma. Anetumab ravtansine is a monoclonal antibody, called anetumab, linked to a chemotherapy drug, called ravtansine. Anetumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as mesothelin receptors, and delivers ravtansine to kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and anetumab ravtansine may work better in treating patients with mesothelin-positive pleural mesothelioma.
Detailed Description: PRIMARY OBJECTIVES: I. Determine the dose of anetumab ravtansine that is safe in combination with pembrolizumab to be used in the randomized phase 2 study. (Phase I safety lead-in) II. Determine if the overall response rate of the combination of anetumab ravtansine and pembrolizumab is superior to pembrolizumab alone. (Phase II) SECONDARY OBJECTIVES: I. To determine the progression free survival of anetumab ravtansine and pembrolizumab compared to pembrolizumab alone. II. To evaluate the pharmacodynamic effects of anetumab ravtansine and pembrolizumab on soluble megakaryocyte potentiating factor (MPF). III. To evaluate the pharmacokinetics of anetumab ravtansine and pembrolizumab. IV. To evaluate mononuclear phagocyte system (MPS) function, FcgammaRs, hormone and chemokine mediators as methods to evaluate factors affecting the pharmacokinetics and pharmacodynamics of these agents. V. To determine the incidence of antibodies directed against anetumab ravtansine. CORRELATIVE STUDY OBJECTIVES: I. To determine whether elevations in Bim in tumor-reactive T cells (TTR) predict responses to treatment and whether its detection is dynamic with treatment. II. To determine whether soluble PD-L1 predicts responses to treatment and whether its detection is dynamic with treatment. III. To evaluate PD-L1 expression in archival tissue as a predictive marker of response to pembrolizumab-based therapy. IV. To explore the symptomatic adverse events (AE) for tolerability of each treatment group using Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE). OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Upon radiologic documentation of disease progression, patients may cross over to Group II. GROUP II: Patients receive anetumab ravtansine IV over 1 hour and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 12 months for anetumab ravtansine and up to 24 months for pembrolizumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 months.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
Mayo Clinic in Arizona, Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center, Duarte, California, United States
UC San Diego Moores Cancer Center, La Jolla, California, United States
Los Angeles General Medical Center, Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
USC Norris Oncology/Hematology-Newport Beach, Newport Beach, California, United States
UCHealth University of Colorado Hospital, Aurora, Colorado, United States
UM Sylvester Comprehensive Cancer Center at Aventura, Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables, Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach, Deerfield Beach, Florida, United States
Mayo Clinic in Florida, Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall, Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation, Plantation, Florida, United States
Northwestern University, Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States
University of Kentucky/Markey Cancer Center, Lexington, Kentucky, United States
University of Maryland/Greenebaum Cancer Center, Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
Mayo Clinic in Rochester, Rochester, Minnesota, United States
Siteman Cancer Center at West County Hospital, Creve Coeur, Missouri, United States
Washington University School of Medicine, Saint Louis, Missouri, United States
Siteman Cancer Center-South County, Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital, Saint Peters, Missouri, United States
Duke University Medical Center, Durham, North Carolina, United States
University of Pittsburgh Cancer Institute (UPCI), Pittsburgh, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas, Dallas, Texas, United States
Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah, United States
University Health Network-Princess Margaret Hospital, Toronto, Ontario, Canada
Name: Aaron S Mansfield
Affiliation: Dana-Farber - Harvard Cancer Center LAO
Role: PRINCIPAL_INVESTIGATOR