Clinical Trial - NCT02658981

Anti-LAG-3 Alone & in Combination w/ Nivolumab Treating Patients w/ Recurrent GBM (Anti-CD137 Arm Closed 10/16/18)

Active, not recruiting

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators: National Cancer Institute (NCI), Bristol-Myers Squibb

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02658981

Protocol Info

Short Description: ABTC-1501 ANTI-LAG-3 OR ANTI-CD137 IN GBM
Long Description: A Phase I Trial of Anti-LAG-3 or Anti-CD137 Alone and in Combination with Anti-PD-1 in Patients with Recurrent GBM
MGH Status: Open
Sponsor: Coop/ABTC
Disease Program: Brain/CNS

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

This phase I trial studies the safety and best dose of anti-LAG-3 (anti-LAG-3 monoclonal antibody BMS-986016) or urelumab alone and in combination with nivolumab in treating patients with glioblastoma that has returned (recurrent). Anti-LAG-3 monoclonal antibody BMS-986016, urelumab, and nivolumab are antibodies (a type of protein) that may stimulate the cells in the immune system to attack tumor cells. It is not yet known whether anti-LAG-3 monoclonal antibody BMS-986016 or urelumab alone or in combination with nivolumab may kill more tumor cells. (The Anti-CD137 antibody (BMS-663513 - urelumab) treatment arm closed by BMS on 10/16/18 due to closure of BMS Urelumab development program. Subjects currently on treatment may continue.)
Condition Title Intervention Phase
Glioblastoma Gliosarcoma Recurrent Brain Neoplasm Anti-LAG-3 Monoclonal Antibody BMS 986016 Anti-PD-1 Pharmacological Study Laboratory Biomarker Analysis Anti-CD137 Phase 1
Study Type Interventional
Official Title A Phase I Trial of Anti-LAG-3 or Anti-CD137 Alone and in Combination With Anti-PD-1 in Patients With Recurrent GBM

Primary Outcome Measures

Maximum tolerated dose (MTD) of anti-LAG-3 monoclonal antibody BMS-986016 as monotherapy as determined by frequency of toxicity [Time Frame: 4 weeks] [Designated as safety issue: ]

Maximum tolerated dose (MTD) of anti-CD137 as monotherapy as determined by frequency of toxicity [Time Frame: 4 weeks] [Designated as safety issue: ]

MTD of Anti-LAG-3 + Anti-PD-1 as determined by frequency of toxicity [Time Frame: 4 weeks] [Designated as safety issue: ]

MTD of Anti-CD137 + Anti-PD-1 as determined by frequency of toxicity [Time Frame: 4 weeks] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Survival [Time Frame: 2 years or until time of death, whichever occurs first] [Designated as safety issue: ]

Progression-free survival rate [Time Frame: 1 year] [Designated as safety issue: ]

Overall Response, assessed by RANO and iRANO [Time Frame: up to 2 years] [Designated as safety issue: ]

Overall Response to anti-LAG-3 monoclonal antibody BMS-98601, assessed by RANO and iRANO [Time Frame: up to 2 years] [Designated as safety issue: ]

Overall Response to anti-CD137 as monotherapy, assessed by RANO and iRANO [Time Frame: up to 2 years] [Designated as safety issue: ]

Overall Response to Anti-LAG-3 + Anti-PD-1, assessed by RANO and iRANO [Time Frame: up to 2 years] [Designated as safety issue: ]

Estimated Enrollment: 63
Study Start Date: August 2016
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: January 2021
Arms Assigned Interventions

Experimental:A1 Anti-LAG-3

Patients receive Anti-LAG-3 monoclonal antibody BMS-986016 IV over 60 minutes and on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Pharmacological Study Laboratory Biomarker Analysis
Other:Laboratory Biomarker Analysis
Correlative Studies

Experimental:A2 Anti-CD137 (Urelumab)

Patients receive Anti-CD137 (Urelumab) IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity Pharmacological Study Laboratory Biomarker Analysis
Biological:Anti-CD137
Given IV

Experimental:B1 Anti-LAG3 + Anti-PD-1 (nivolumab)

Patients receive Anti-PD-1 (nivolumab) IV over 60 minutes and anti-LAG-3 monoclonal antibody BMS-986016 IV on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Pharmacological Study Laboratory Biomarker Analysis
Biological:Anti-PD-1
Given IV

Experimental:B2 Anti-CD137 + Anti-PD-1

Patients receive Anti-PD-1 (nivolumab) IV over 60 minutes on days 1 and 15 and Anti-CD137 (urelumab) IV on day 1. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. (2pts enrolled before the Anti-CD137 antibody (BMS-663513 - urelumab) treatment arm closed by BMS on 10/16/18 due to closure of BMS Urelumab development program. Subjects currently on treatment may continue.) Pharmacological Study Laboratory Biomarker Analysis

Experimental:Intratumoral Studies

Patients pre-operatively receive either anti-LAG-3 monoclonal antibody BMS-986016 (Arm A1), or urelumab (Arm A2), or nivolumab and anti-LAG-3 monoclonal antibody BMS-986016 as in Part B (B1)), or nivolumab and urelumab as in Part B (B2). Within 45 days of surgical resection, patients post-operatively receive drug from one of the four arms. (3pts enrolled before the Anti-CD137 antibody (BMS-663513 - urelumab) treatment arm closed by BMS on 10/16/18 due to closure of BMS Urelumab development program. Subjects currently on treatment may continue.)

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy and temozolomide
  • Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction [MSPCR] or quantitative polymerase chain reaction [PCR]) are acceptable
  • Patients must have measurable contrast-enhancing disease (defined as at least 1 cm x 1 cm) by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment (patients may have gross total resection, but should have measurable disease post-operatively); patients must be able to undergo MRI of the brain with gadolinium; patients must be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to this baseline MRI
  • Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
  • Patients must have recovered from severe toxicity of prior therapy; an interval of at least 12 weeks must have elapsed since the completion of radiation therapy or placement of Gliadel wafers, and at least 6 weeks must have elapsed from the last dose of temozolomide (TMZ); no prior therapies are allowed other than radiation, temozolomide, and Gliadel wafers (placed during the first surgery at diagnosis of GBM)
  • Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • Absolute lymphocyte count >= 1000/ul
  • Absolute neutrophil count >= 1,500/ul
  • Platelets >= 100,000/ul
  • Hemoglobin >= 9 g/dl
  • Total bilirubin =< institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73m^2 for patients with creatinine levels above institutional normal
  • Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
  • Patients must be able to provide written informed consent
  • Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to treatment start; women of childbearing potential must agree to use two methods of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and through 23 weeks after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 31 weeks after the last dose of study drug
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years

Exclusion Criteria:

  • Patients receiving any other investigational agents are ineligible
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-LAG-3, anti-CD137, and anti-PD1 are ineligible; the investigator brochures can be referenced for more information
  • Patients with active or recent history of known or suspected autoimmune disease are ineligible; subjects with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, and skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment, are permitted to enroll
  • Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study entry are ineligible
  • Patients must not be receiving greater than 1 mg dexamethasone/day (or an equivalent amount of an alternative corticosteroid) for at least 1 week prior to treatment start
  • Patients must have no evidence of mass effect and no midline shift
  • Patients must have no evidence of significant hematologic, renal, or hepatic dysfunction; patients with underlying hepatocellular disease should be given careful risk/benefit consideration prior to enrollment; patients with a history of any chronic hepatitis as evidenced by the following are ineligible:
  • Positive test for hepatitis B surface antigen (HBsAg)
  • Positive test for qualitative hepatitis C viral load (by PCR) (Note: subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible; history of resolved hepatitis A virus infection is not an exclusion criterion)
  • History of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis, or any form of chronic liver disease
  • Patients must be hepatitis C virus (HCV) negative (by quantitative PCR [qPCR]) and hepatitis B virus core antibody (HBcAb) negative (no prior hepatitis B infection)
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with these agents
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02658981

Locations

  • United States, Alabama
    • UAB Comprehensive Cancer Center Birmingham, Alabama, United States, 35294-3410
  • United States, California
    • Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California, United States, 90095
  • United States, Maryland
    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231
  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114
    • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115
  • United States, Michigan
    • Henry Ford Hospital Detroit, Michigan, United States, 48202
  • United States, New York
    • Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10021
  • United States, North Carolina
    • Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina, United States, 27157-1096
  • United States, Ohio
    • Cleveland Clinic Taussig Cancer Center Cleveland, Ohio, United States, 44195
  • United States, Pennsylvania
    • Abrams Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104
    • Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

National Cancer Institute (NCI)

Bristol-Myers Squibb

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02658981
Other Study ID Numbers: IRB00095527
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Glioblastoma

Gliosarcoma

Brain Neoplasms

Nivolumab

Antibodies

Antibodies, Monoclonal

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on November 12, 2020