ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Mogamulizumab + Nivolumab in Subjects w/Locally Advanced or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02705105
Recruitment Status : Active, not recruiting
First Posted : March 10, 2016
Last Update Posted : March 29, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Kyowa Kirin Pharmaceutical Development, Inc.

Brief Summary:
The purpose of this study is to characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or the recommended fixed dose of the combinations of mogamulizumab and nivolumab in subjects with locally advanced or metastatic solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor Cancer Carcinoma Hepatocellular Carcinoma HCC Biological: Mogamulizumab + Nivolumab Phase 1 Phase 2

Detailed Description:

This is a multicenter, Phase 1/2 open-label, dose-finding and cohort expansion study of the anti-CCR4 antibody mogamulizumab in combination therapy with the anti-PD-1 antibody nivolumab in adult subjects with locally advanced or metastatic solid tumors.

Phase 1 will identify the maximum tolerated dose (MTD) or the highest protocol-defined dose in absence of exceeding the MTD, of the combination regimen of mogamulizumab and nivolumab subjects. Phase 1 will enroll up to 12 subjects. Phase 2 will explore the safety, efficacy and anti-tumor activity of the highest tolerated dose of the combination regimen. Phase 2 will enroll up to 184 subjects.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination With Nivolumab in Subjects With Locally Advanced or Metastatic Solid Tumors
Study Start Date : December 2015
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Mogamulizumab + Nivolumab

During parts 1 and 2, mogamulizumab and nivolumab are administered at appropriate intervals.

Part 1 (Dose Escalation Part): During cohort 1 to 2, mogamulizumab and nivolumab are administered in combination.

Part 2 (Expansion Part): Patients will be treated with maximum tolerated dose established in the dose escalation part for each combination.

Biological: Mogamulizumab + Nivolumab
i.v. administration
Other Name: Mogamulizumab: KW-0761, Nivolumab: ONO-4538/BMS-936558




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: From the first dose of study medications until 14 days after the last dose of study medication ]
    combination regimen of mogamulizumab and nivolumab in subjects with locally advanced or metastatic solid tumors.

  2. Number of subjects experiencing dose-limiting toxicity [ Time Frame: From the first dose of study medications until 14 days after the last dose of study medication ]
    combination of mogamulizumab and nivolumab


Secondary Outcome Measures :
  1. Objective tumor response rate according to RECIST [ Time Frame: From baseline to every 12 weeks, until data cut off ]
    combination of mogamulizumab and nivolumab



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Subject is age 18 years or older;
  • Subject must have histologically or cytologically confirmed solid tumor;
  • Subject must have locally advanced or metastatic solid tumor;
  • Subjects who have progressed or have been intolerant to any standard treatment regimen or refused standard treatment, or for which adequate standard therapy does not exist.
  • Subjects who have evaluable lesion per guideline of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1;
  • If the subject is a woman of child-bearing potential or man who is sexually active with woman of child-bearing potential, the subject agrees to use adequate contraception from signing of the ICF, for the duration of study participation; and for 23 weeks after the last dose of IMP for women or 31 weeks after the last dose of IMP for men;
  • Subjects who have adequate hematological, renal, hepatic and respiratory functions defined.
  • The subject is willing to undergo tumor biopsy during the Screening period, or if the tumor is inaccessible for biopsy, archived tumor material must be available for submission;
  • Subjects who voluntarily signed and dated Institutional Review Board approved informed consent form in accordance with regulatory and institutional guidelines.

Hepatocellular Carcinoma Inclusion Criteria:

  • Histologically confirmed hepatocellular carcinoma not amenable for management with curative intent by surgery or local therapeutic measure;
  • Subject must have received sorafenib treatment and either:

    • have had documented radiographic or symptomatic progression during or after sorafenib therapy; OR
    • be intolerant of sorafenib (defined as Grade 2 drug-related adverse event which 1) persisted in spite of comprehensive supportive therapy according to institutional standards AND 2) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily) AND/OR Grade 3 drug-related adverse event which 1) persisted in spite of comprehensive supportive therapy according to institutional standards OR 2) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily); OR must have documented refusal of sorafenib;
  • Subject has Child-Pugh score of ≤6, i.e., Child-Pugh A (Appendix 2);
  • INR ≤ 2.3 or Prothrombin time (PT) ≤ 6 seconds above control;
  • Subject has HBV DNA viral load undetectable or < 100 IU/mL at screening. If subject has detectable HBsAg, HBeAg, or HBV DNA (indicating ongoing viral replication of hepatitis B, he/she must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy. If not on antiviral therapy at screening, then the subject must initiate treatment per regional standard of care guidelines prior to C1D1 and must be willing to continue antiviral therapy while on study treatment.

Exclusion Criteria

  • Female subject who is pregnant or breast-feeding, or any subject expecting to conceive or father a child during this study;
  • Subjects with uncontrolled and significant inter-current illness.
  • Subjects has psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirements;
  • Subject has primary central nervous system (CNS) tumor or known CNS metastases and/or history of CNS metastases and/or carcinomatous meningitis; Exception: Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be off corticosteroids for 4 weeks prior to enrollment.
  • Subject has received prior therapy for cancer or major surgery within 28 days, or 42 days for nitrosourea or mitomycin C, prior to Cycle 1 Day 1, or 14 days for tamoxifen;
  • Subject has received radiotherapy or radiosurgery within 14 days prior to Cycle 1 Day 1;
  • Subject has been previously treated with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways;
  • Subject has been previously treated with mogamulizumab;
  • Subject has a history of allergy or hypersensitivity to study drug components;
  • Subject has received a live, attenuated vaccine within 28 days prior to Cycle 1 Day 1;
  • Subject has a history of organ transplant or allogeneic bone marrow transplant;
  • Subject has any unresolved toxicity Grade > 1 from previous anti-cancer therapy
  • Subject use of immunosuppressive medication within 14 days before Cycle 1 Day 1.
  • Subjects who have known active autoimmune disease or a history of autoimmune disease which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids;
  • Subjects who have history of toxic epidermal necrolysis or Stevens-Johnson syndrome;
  • Subjects who have a history of inflammatory bowel disease, Crohn's disease, ulcerative colitis, or Wegener's granulomatosis;
  • Subject has primary or acquired immunodeficiency or known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome;
  • Subject who tests positive for hepatitis B surface antigen (HBVsAg) or hepatitis C RNA indicating acute or chronic infection except for subjects with hepatocellular carcinoma;
  • Subject has another active malignancy requiring concurrent intervention;
  • Subject who is receiving any other investigational agents;
  • Subject has another condition that, in the opinion of the Investigator and/or Sponsor, would interfere with evaluation of the IMP or interpretation of subject safety or study results;
  • Subject has a history of pneumonitis or interstitial lung disease.

Hepatocellular Carcinoma Exclusion Criterion:

  • Any history of hepatic encephalopathy
  • Any prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires paracentesis for control;
  • Active coinfection with both hepatitis B (i.e., HBVsAg and/or hepatitis B DNA) and hepatitis C (i.e., hepatitic C RNA)
  • Hepatitis D infection in subjects with hepatitis B
  • Any history of clinically meaningful variceal bleeding within the last three months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02705105


Locations
United States, Arizona
Gilbert, Arizona, United States, 85234
United States, California
Greenbrae, California, United States, 94904
Los Angeles, California, United States, 90033
United States, Florida
Jacksonville, Florida, United States, 32224
United States, Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Maryland
Baltimore, Maryland, United States, 21205
United States, Michigan
Kalamazoo, Michigan, United States, 49007
United States, New Jersey
Piscataway, New Jersey, United States, 08854
United States, New Mexico
Albuquerque, New Mexico, United States, 87106
United States, North Carolina
Goldsboro, North Carolina, United States, 27534
United States, Ohio
Columbus, Ohio, United States, 43210
United States, Oregon
Portland, Oregon, United States, 97213
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
Kyowa Kirin Pharmaceutical Development, Inc.
Bristol-Myers Squibb

Responsible Party: Kyowa Kirin Pharmaceutical Development, Inc.
ClinicalTrials.gov Identifier: NCT02705105     History of Changes
Other Study ID Numbers: 0761-014
First Posted: March 10, 2016    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Keywords provided by Kyowa Kirin Pharmaceutical Development, Inc.:
Metastatic Solid Tumors
Advanced Solid Tumors
KW-0761
ONO-4538/BMS-936558
Anti-tumor
Mogamulizumab
Nivolumab
Oncology
HCC
Hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs