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

NCT02705105 | Completed Phase 1 Results DMC

• 1 other identifier: 0761-014
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 15

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.

Conditions

Solid Tumor; Cancer; Carcinoma; Hepatocellular Carcinoma; HCC

Keywords

Metastatic Solid Tumors; Advanced Solid Tumors; KW-0761; ONO-4538/BMS-936558; Anti-tumor; Mogamulizumab; Nivolumab; Oncology; HCC; Hepatocellular carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  The MTD was defined as one dose level below the dose level of the cohort where ≥ one-third of the subjects experienced a dose-limiting toxicity (DLT)

  From the first dose of study medications until 14 days after the last dose of study medication

• Number of Subjects Experiencing Dose-limiting Toxicity

  combination of mogamulizumab and nivolumab

  From the first dose of study medications until 14 days after the last dose of study medication

Secondary Outcomes (1)

• Objective Tumor Response Rate According to RECIST

  From baseline to every 12 weeks, until data cut off

Study Arms (2)

Dose-Finding Cohort

EXPERIMENTAL

Cycle 1 Days 1, 8, 15, and 22: Dose Level 1 of Mogamulizumab + Nivolumab Subsequent Cycles Days 1 and 15: Dose Level 1 of Mogamulizumab + Nivolumab If \>1 patient has a DLT at first dose level, then the following cohort will be enrolled: Cycle 1 Days 1, 8, 15, and 22: Optional Dose Level of Mogamulizumab + Nivolumab Subsequent Cycles Days 1 and 15: Optional Dose Level of Mogamulizumab + Nivolumab

Biological: Mogamulizumab + Nivolumab

Expansion Cohort

EXPERIMENTAL

Cycle 1 Days 1, 8, 15, and 22: Maximum Tolerated Dose of Mogamulizumab + Nivolumab Subsequent Cycles Days 1 and 15: Maximum Tolerated Dose of Mogamulizumab + Nivolumab Subjects will be separated further into cohorts by tumor type

Biological: Mogamulizumab + Nivolumab

Interventions

Mogamulizumab + Nivolumab BIOLOGICAL

i.v. administration

Also known as: Mogamulizumab: KW-0761, Nivolumab: ONO-4538/BMS-936558

Dose-Finding Cohort; Expansion Cohort

Eligibility Criteria

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

You may qualify if:

• 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.
• 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);

You may not qualify if:

• 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;

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (15)

Unknown Facility

Gilbert, Arizona, 85234, United States

Location

Unknown Facility

Greenbrae, California, 94904, United States

Location

Unknown Facility

Los Angeles, California, 90033, United States

Location

Unknown Facility

Jacksonville, Florida, 32224, United States

Location

Unknown Facility

Augusta, Georgia, 30912, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Baltimore, Maryland, 21205, United States

Location

Unknown Facility

Kalamazoo, Michigan, 49007, United States

Location

Unknown Facility

Piscataway, New Jersey, 08854, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87106, United States

Location

Unknown Facility

Goldsboro, North Carolina, 27534, United States

Location

Unknown Facility

Columbus, Ohio, 43210, United States

Location

Unknown Facility

Portland, Oregon, 97213, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma; Carcinoma, Hepatocellular

Interventions

mogamulizumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

A decision was made by the Sponsor and Collaborator (BMS) in March of 2018 to stop enrollment in Phase 2 of study despite not all cohorts having reached the Stage 1 target enrollment.

Results Point of Contact

• Title: Kyowa Kirin Pharmaceutical Development
• Organization: Kyowa Kirin Pharmaceutical Development

kkd.clintrial.82@kyowakirin.com

609-919-1100

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 10, 2016
• Study Start: February 1, 2016
• Primary Completion: August 22, 2018
• Study Completion: October 10, 2018
• Last Updated: April 25, 2024
• Results First Posted: June 4, 2020

Record last verified: 2024-04

Locations

US (15)