Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma

NCT ID: NCT02723006

Last Updated: 2024-03-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-22
• Study Completion Date: 2018-05-11

Brief Summary

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.

Detailed Description

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.

Conditions

Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

TAK-580 + nivolumab

TAK-580 orally, once weekly along with nivolumab, intravenous, every 2 weeks.

Group Type: EXPERIMENTAL

TAK-580

Intervention Type: DRUG

TAK-580 tablets

nivolumab

Intervention Type: DRUG

nivolumab infusion

TAK-202 (plozalizumab) + nivolumab

TAK-202 (plozalizumab) 2 milligram (mg), intravenous, once in Week 1, 3, 5, 9, and every 4 weeks thereafter with nivolumab infusion, intravenous, every 2 weeks.

Group Type: EXPERIMENTAL

TAK-202

Intervention Type: DRUG

TAK-202 infusion

nivolumab

Intervention Type: DRUG

nivolumab infusion

vedolizumab + nivolumab + ipilimumab

Vedolizumab intravenous, once in Week 1, 3, 5, and 13 along with nivolumab infusion, intravenous, once in Week 1, 4, 7, 10, and 13 and every 2 weeks thereafter, along with ipilimumab intravenous, once in Week 1, 4, 7, and 10.

Group Type: EXPERIMENTAL

vedolizumab

Intervention Type: DRUG

vedolizumab infusion

nivolumab

Intervention Type: DRUG

nivolumab infusion

ipilimumab

Intervention Type: DRUG

ipilimumab infusion

Interventions

TAK-580

TAK-580 tablets

Intervention Type: DRUG

TAK-202

TAK-202 infusion

Intervention Type: DRUG

vedolizumab

vedolizumab infusion

Intervention Type: DRUG

nivolumab

nivolumab infusion

Intervention Type: DRUG

ipilimumab

ipilimumab infusion

Intervention Type: DRUG

Other Intervention Names

MLN2480; MLN1202; plozalizumab; Entyvio; Opdivo; Yervoy

Eligibility Criteria

Inclusion Criteria

1. Is a male or female participant of 18 years or older.

2. Has histologically confirmed, unresectable Stage III or Stage IV melanoma per the American Joint Committee on Cancer (AJCC) staging system.

3. Has an eastern cooperative oncology group (ECOG) performance status of 0-1.

4. Adequate bone marrow reserve and renal and hepatic function within 28 days before the first dose of study drug on the basis of the defined laboratory parameters.

5. For TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only: Had disease accessible for repeat nonsignificant risk biopsy (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures extending beyond the esophagus, stomach, or bowel) and willingness to undergo serial tumor biopsies.

6. Additional Inclusion Requirements for TAK-580 + nivolumab

a) BRAF V600 mutation-positive or NRAS mutation-positive disease previously untreated with RAF, MEK, or other inhibitors of the mitogen-activated protein kinase (MAPK) pathway. Participants who have progressed on these agents can still be enrolled in TAK-202 (plozalizumab) + nivolumab or vedolizumab + nivolumab + ipilimumab.

7. Additional Inclusion Requirements for expansion cohorts only a) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1) and at least 1 nonsignificant risk, non-target lesion accessible for biopsy per the guidelines above (for TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only).

Exclusion Criteria

1. Has active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (greater than [>] 10 milligram per day [mg/day] prednisone equivalents) for at least 2 weeks prior to study drug administration.

2. Completed a prior therapy less than (<) 2 weeks prior to first dose and for whom adverse events (AEs) related to prior therapy had not returned to baseline or improved to Grade 1.

3. Has active, known or suspected autoimmune disease.

4. Has a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.

5. Has a history of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis (including pneumonitis), interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.

6. Is previously diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B or C.

7. Additional Exclusion Requirements for arm 1 only (nivolumab Plus TAK-580)

1. Concomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580.

2. Treatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580.

3. Left ventricular ejection fraction (LVEF) <50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.

4. Known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of the TAK-580.

8. Additional Exclusion Requirements for arm 3 only (vedolizumab Plus nivolumab Plus ipilimumab)

1. Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab.

2. Has a history of any major neurological disorders, including stroke, multiple sclerosis, or neurodegenerative disease.

3. Has taken any live vaccinations within 30 days before study drug administration except for the influenza vaccine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

University of Arizona Cancer Center

Tucson, Arizona, United States

University of California Los Angeles - Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

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

Saint Luke's Cancer Center - Bethlehem

Easton, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Inova Fairfax Hospital

Fairfax, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U1111-1177-4142

Identifier Type: OTHER

Identifier Source: secondary_id

2015-005554-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C28003

Identifier Type: -

Identifier Source: org_study_id