Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma

NCT03927105 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BTCRC-HEM16-085
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

A multicenter trial evaluating the combination of nivolumab and the antagonistic CSF-1R monoclonal antibody cabiralizumab (BMS-986227) in patients with relapsed/refractory peripheral T cell lymphoma

Conditions

Peripheral T Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) at Four Months (LYRIC Criteria)

  Overall Response Rate (CR + PR) as determined by LYRIC (LYmphoma Response to Immunomodulatory therapy Criteria), at four months (shown as number of participants with CR or PR at 4 months). LYRIC: An adaptation of the Lugano classification developed because discriminating true progressive disease from pseudoprogression in lymphoma patients receiving immunomodulatory agents is challenging. To address this challenge, the LYRIC criteria incorporated the response category of "indeterminate response" (IR). * IR(1): ≥ 50% increase in overall tumor burden (sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites) occurred in the 1st 12 weeks of therapy and without clinical deterioration * IR(2): new lesions or ≥ 50% increase of existing lesion(s) without a ≥ 50% increase of overall tumor burden at any time during treatment. * IR(3): increased FDG uptake of 1or more lesions without any increase in size or number of those lesions.

  4 months

• Complete Response Rate (CRR) at Four Months

  Complete response rate, as determined by LYRIC criteria, at four months (reported as number of participants with CR at 4 months). LYRIC: An adaptation of the Lugano classification developed because discriminating true progressive disease from pseudoprogression in lymphoma patients receiving immunomodulatory agents is challenging. To address this challenge, the LYRIC criteria incorporated the response category of "indeterminate response" (IR). * IR(1): ≥ 50% increase in overall tumor burden (sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites) occurred in the 1st 12 weeks of therapy and without clinical deterioration * IR(2): new lesions or ≥ 50% increase of existing lesion(s) without a ≥ 50% increase of overall tumor burden at any time during treatment. * IR(3): increased FDG uptake of 1or more lesions without any increase in size or number of those lesions.

  4 months

Secondary Outcomes (7)

• Overall Response at Four Months by (LUGANO 2014) Criteria

  four months

• Complete Response Rate at Four Months (LUGANO 2014) Criteria

  four months

• Progression-Free Survival (PFS)

  3, 6, 9 and 12 months post starting study treatment

• Disease Control Rate (DCR)

  at time of study drug discontinuation, average of 7 months

• Duration of Response (DOR)

  at time of study drug discontinuation, up to 3 years

Study Arms (1)

Nivolumab + Cabiralizumab

EXPERIMENTAL

Nivolumab 240mg IV + Cabiralizumab 4mg/kg on day 1 of every 14 day cycle.

Drug: Nivolumab; Drug: cabiralizumab

Interventions

Nivolumab DRUG

Nivolumab is a human monoclonal antibody (HuMAb; immunoglobulin G4 \[IgG4\]-S228P) that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.1 Binding of PD-1 to its ligands, programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-antigens. Nivolumab will be delivered intravenously at a fixed dose of 240 mg on day 1 of 14 day cycles.

Also known as: Opdivo, BMS-936558, MDX1106

Nivolumab + Cabiralizumab

cabiralizumab DRUG

Cabiralizumab is a recombinant, humanized Immunoglobulin G4 (IgG4) monoclonal antibody that binds to human colony stimulating factor 1 receptor (CSF1R; c-fms). Cabiralizumab will be delivered intravenously at a dosage of 4 mg/kg on day 1 of 14 day cycles.

Also known as: BMS-986227, FPA008

Nivolumab + Cabiralizumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent for clinical trial enrollment and mandatory consent for any biopsies as well as HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2.
• Histological confirmation of peripheral T-cell lymphoma (PTCL) except adult T-cell leukemia/lymphoma (ATLL).
• Documented disease progression after receiving at least two prior therapeutic regimen including brentuximab vedotin in patients with CD30 positive disease (defined as \>10% CD30 positive cells).
• Prior cancer treatment must be completed at least 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ grade 1 or baseline. Systemic steroids at a dose less than the equivalent of 10 mg/day of prednisone and inhaled, nasal, and topical steroids are permitted. Adrenal replacement steroid doses \> 10 mg daily prednisone equivalent in the absence of active autoimmune disease are permitted. Treatment with a short course of steroids (\< 5 days) up to 7 days prior to study registration is permitted. Intermittent dexamethasone for the treatment of nausea/emesis is also permitted.
• Demonstrate adequate organ function as defined in the table in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin) performed at screening and within 24 hours of first dose of investigational treatment. See Section 5.4.1 of the protocol for definition of childbearing potential.
• Females of childbearing potential must be willing to abstain from heterosexual activity or use an effective method of contraception from the time of informed consent until 5 months after the last dose of investigational product. See Section 5.4.1 of the protocol for methods of contraception.
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drugs and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. See Section 5.4.1 of the protocol for methods of contraception.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

You may not qualify if:

• PTCL histology consistent with ATLL.
• A history of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study.
• Active infection requiring systemic therapy
• Recent (\<100 days) autologous stem cell transplant, or previous allogeneic stem cell transplant.
• Known positive test for HIV. NOTE: HIV screening is not required.
• History of any chronic hepatitis as evidenced by the following:
• Positive test for hepatitis B surface antigen
• Positive test for qualitative hepatitis C viral load (by polymerase chain reaction \[PCR\]).
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• Previous malignancies (except non-melanoma skin cancers and in situ bladder, gastric, colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period.
• Prior treatment with cabiralizumab (or other CSF1R pathway inhibitors).
• Prior treatment with nivolumab or other medications within the checkpoint blockade family.
• Any unregulated nutritional or herbal supplement or recreational drug within 2 weeks prior to registration which, in the opinion of the study investigator, has the potential to cause hepatic injury.
• Concomitant use of statins for treatment of hypercholesterolemia. Statins are allowed only if the patient is on a stable dose for over 3 months prior to study registration and is in a stable status without CK elevations.
• Non-oncology vaccine therapies for prevention of infectious diseases (e.g., human papilloma virus vaccine) within 4 weeks of study registration. The inactivated seasonal influenza vaccine can be given to patients before treatment and while on therapy without restriction. Influenza vaccines containing live virus or other clinically indicated vaccinations for infectious diseases (i.e., pneumovax, varicella, etc.) may be permitted, but must be discussed with the sponsor investigator and may require a study drug washout period before and after administration of vaccine.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Unviersity of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

Nivolumab; cabiralizumab

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System 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: Adelai Neal
• Organization: Hoosier Cancer Research Network

aneal@hoosiercancer.org

317-921-2053

Study Officials

• Ryan Wilcox, MD, PhD

  University of Michigal Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 25, 2019
• Study Start: April 25, 2019
• Primary Completion: November 1, 2019
• Study Completion: July 6, 2023
• Last Updated: May 7, 2026
• Results First Posted: September 10, 2021

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)