The purpose of this study is to determine the initial safety profile and initial antitumor activity of the combination treatments (immune checkpoint inhibitors \[nivolumab, ipilimumab\] with investigational drugs \[TAK-580, TAK-202 (plozalizumab), vedolizumab\]) in the 3 arms when administered to participants with advanced melanoma.
The drugs being tested in this study are called TAK-580, TAK-202 (plozalizumab), and vedolizumab. These investigational drugs were given along with standard of care checkpoint inhibitors (\[nivolumab in Arms 1 and 2\] or nivolumab + ipilimumab in Arm 3). This study looked at the safety profile of the combination treatments in each arm when administered to participants with metastatic melanoma. The study planned to enroll approximately 156 participants. Participants were assigned to one of the 3 treatment groups: * TAK-580 + nivolumab * TAK-202 (plozalizumab) + nivolumab * vedolizumab + nivolumab + ipilimumab This study consists of 3 parts. A dose-escalation safety lead-in phase, confirmatory safety phase and a cohort expansion phase. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 50 weeks. Participants may make multiple visits to the clinic and 30, 60, and 90 days after last dose of study drug for follow-up assessments.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
22
University of Arizona Cancer Center
Tucson, Arizona, United States
University of California Los Angeles - Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Number of Dose Limiting Toxicities (DLTs) During the Dose-escalation Safety Lead-in Phase
DLTs was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7
Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase
ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. was the percentage of participants with complete response (CR) or partial response (PR). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
Time frame: Baseline up to Week 50
Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase
DOR based on RECIST version 1.1 was the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From date of first documented confirmed CR/PR until date of first documentation of PD or death (up to Week 50)
Progression-free Survival (PFS) During the Dose-escalation Safety Lead-in Phase
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nivolumab infusion
ipilimumab infusion
University of California San Francisco Medical Center
San Francisco, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Emory University Hospital
Atlanta, Georgia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
New York University Langone Medical Center
New York, New York, United States
...and 4 more locations
PFS was the time from first dose date to date of the first documentation of confirmed PD or death, whichever occurred first. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions.
Time frame: From first dose date to the date of the first documentation of confirmed PD or death (up to Week 50)
Overall Survival (OS) During the Dose-escalation Safety Lead-in Phase
OS was the time from date of first dose of study drug until date of death from any cause.
Time frame: From first dose of study drug until date of death from any cause (up to Week 50)
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50)