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

NCT02723006 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: C28003U1111-1177-41422015-005554-35
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 14

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.

Conditions

Melanoma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7

Secondary Outcomes (5)

• Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase

  Baseline up to Week 50

• Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase

  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

  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

  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)

  From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50)

Study Arms (3)

TAK-580 + nivolumab

EXPERIMENTAL

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

Drug: TAK-580; Drug: nivolumab

TAK-202 (plozalizumab) + nivolumab

EXPERIMENTAL

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.

Drug: TAK-202; Drug: nivolumab

vedolizumab + nivolumab + ipilimumab

EXPERIMENTAL

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.

Drug: vedolizumab; Drug: nivolumab; Drug: ipilimumab

Interventions

TAK-580 DRUG

TAK-580 tablets

Also known as: MLN2480

TAK-580 + nivolumab

TAK-202 DRUG

TAK-202 infusion

Also known as: MLN1202, plozalizumab

TAK-202 (plozalizumab) + nivolumab

vedolizumab DRUG

vedolizumab infusion

Also known as: Entyvio

vedolizumab + nivolumab + ipilimumab

nivolumab DRUG

nivolumab infusion

Also known as: Opdivo

TAK-202 (plozalizumab) + nivolumab; TAK-580 + nivolumab; vedolizumab + nivolumab + ipilimumab

ipilimumab DRUG

ipilimumab infusion

Also known as: Yervoy

vedolizumab + nivolumab + ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is a male or female participant of 18 years or older.
• Has histologically confirmed, unresectable Stage III or Stage IV melanoma per the American Joint Committee on Cancer (AJCC) staging system.
• Has an eastern cooperative oncology group (ECOG) performance status of 0-1.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Has active, known or suspected autoimmune disease.
• Has a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
• 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.
• Is previously diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B or C.
• Concomitant use or administration of clinically significant enzyme inducers less than or equal to (\<=) 14 days before the first dose of TAK-580.
• Treatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580.
• 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.
• Known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of the TAK-580.
• Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab.
• Has a history of any major neurological disorders, including stroke, multiple sclerosis, or neurodegenerative disease.
• Has taken any live vaccinations within 30 days before study drug administration except for the influenza vaccine.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (14)

University of Arizona Cancer Center

Tucson, Arizona, United States

Location

University of California Los Angeles - Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Location

University of California San Francisco Medical Center

San Francisco, California, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, United States

Location

Emory University Hospital

Atlanta, Georgia, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Location

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

New York University Langone Medical Center

New York, New York, United States

Location

Saint Luke's Cancer Center - Bethlehem

Easton, Pennsylvania, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Location

Inova Fairfax Hospital

Fairfax, Virginia, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

tovorafenib; plozalizumab; vedolizumab; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2016
• First Posted: March 30, 2016
• Study Start: June 22, 2016
• Primary Completion: May 11, 2018
• Study Completion: May 11, 2018
• Last Updated: March 5, 2024
• Results First Posted: April 1, 2021

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (14)