Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

NCT03816332 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2019-00239ETCTN1021410214UM1CA186691
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

This phase I trial studies how well tacrolimus, nivolumab, and ipilimumab work in treating kidney transplant recipients with cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Tacrolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tacrolimus, nivolumab, and ipilimumab may work better in treating kidney transplant recipients with cancer compared to chemotherapy, surgery, radiation therapy, or targeted therapies.

Conditions

Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8; Metastatic Basal Cell Carcinoma; Metastatic Melanoma; Metastatic Merkel Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8; Unresectable Basal Cell Carcinoma; Unresectable Melanoma; Unresectable Merkel Cell Carcinoma; Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Number (and Percentage) of Outcome Responses After Receiving Nivolumab, Tacrolimus, and Prednisone

  Percentage of kidney transplant recipients who experienced complete response (CR), partial response (PR) or stable disease (SD) without allograft loss.

  At 16 weeks

Secondary Outcomes (6)

• Objective Response (CR or PR) Rate (ORR) After Receiving Nivolumab, Tacrolimus, and Prednisone

  Up to 4 months

• Rate of Allograft Loss After Receiving Nivolumab, Tacrolimus, and Prednisone

  Up to 4 months

• Duration of Progression-free Survival After Receiving Nivolumab, Tacrolimus, and Prednisone

  Up to 4 months

• Duration of Overall Survival After Receiving Nivolumab, Tacrolimus, and Prednisone

  Up to 3 years

• Overall Response Rate (ORR) in Patients After Receiving Ipilimumab, Nivolumab, Tacrolimus, and Prednisone

  Up to 3 years

Study Arms (1)

Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive tacrolimus PO BID and prednisone PO QD. Within 28 days, patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity. Patients who experience PD or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab; Drug: Prednisone; Drug: Tacrolimus

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)

Tacrolimus DRUG

Given PO

Also known as: FK 506, FK-506, FK506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Patients must be kidney transplant recipients with a functioning allograft who do not currently require dialysis
• Patients must have histologically or cytologically confirmed melanoma, basal cell carcinoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma, or microsatellite instability (MSI)-high cancers for which standard non-immunological medical, surgical, or radiation therapy would be insufficient (i.e., patients who are not surgical candidates). This trial is not intended to provide therapy as a neoadjuvant approach
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, i.e., at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm by chest x-ray or as \>= 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam is preferred, but not required. Patients with evaluable disease but no target lesions (e.g., evaluable bone metastases) may be included after discussion with the principal investigator (PI)
• Patients must have documentation, in consultation with the PI, that they received, refused, or were ineligible for the following non-immunologic therapies:
• For patients with:
• BRAF-mutant melanoma: prior therapies include BRAF/MEK inhibitors
• Merkel cell carcinoma: prior therapies include platinum + VP-16
• Basal cell carcinoma: prior therapies include Hedgehog pathway inhibitors
• Cutaneous squamous cell carcinoma: prior therapies include cetuximab
• MSI colorectal carcinoma: prior therapies include: leucovorin calcium, 5-fluorouracil and oxaliplatin (FOLFOX)
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Leukocytes \>= 2,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)

You may not qualify if:

• Patients must not have received a liver, lung, heart, or pancreas transplant; or allogeneic stem cell transplant; or any kind of bone marrow transplant
• Patients must not be unwilling or unable to undergo dialysis
• Patients must not have prior evidence of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies (DSA). Patients with detectable DSA but negative dd-cfDNA may be eligible after consultation with the study PI
• Patients must not have a history of antibody- or cell-mediated allograft rejection within 3 months of study entry
• Patients must not have had chemotherapy or radiotherapy within 4 weeks of study entry or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier
• Patients must not have had prior treatment for their current cancer with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patients must not be receiving any other investigational agents
• Patients must not have known central nervous system (CNS) metastases or leptomeningeal metastases because of poor prognosis and concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other AEs. Patients with brain metastases are permitted to enroll if metastases have been treated and there is no MRI evidence of progression for 4 weeks after treatment is complete and no evidence of progression within 28 days prior to study entry
• Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
• Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with nivolumab or ipilimumab. These potential risks may also apply to other agents used in this study
• Patients must not have active autoimmune disease, or history of autoimmune disease that might recur, which may affect vital organ function, and will only be eligible after consultation with the study PI
• This includes but is not limited to:
• Immune-related neurologic disease,

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (3)

• Schenk KM, Deutsch JS, Chandra S, Davar D, Eroglu Z, Khushalani NI, Luke JJ, Ott PA, Sosman JA, Aggarwal V, Schollenberger MD, Sharfman WH, Bibee KP, Scott JF, Loss MJ, Wang H, Qi H, Sharon E, Streicher H, Chen HX, Woodward RN, Bagnasco SM, Taube JM, Topalian SL, Brennan DC, Lipson EJ. Nivolumab + Tacrolimus + Prednisone +/- Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers. J Clin Oncol. 2024 Mar 20;42(9):1011-1020. doi: 10.1200/JCO.23.01497. Epub 2024 Jan 22.

  PMID: 38252910 DERIVED

• Bonilla M, Gudsoorkar P, Wanchoo R, Herrmann SM, Jhaveri KD. Onconephrology 2022: An Update. Kidney360. 2023 Feb 1;4(2):258-271. doi: 10.34067/KID.0001582022. Epub 2022 Dec 9.

  PMID: 36821617 DERIVED

• Trager MH, Coley SM, Dube G, Khan S, Ingham M, Samie FH, Geskin LJ, McDonnell D, Brouder D, Saenger Y, Carvajal R. Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients. J Immunother Cancer. 2020 Jun;8(1):e000908. doi: 10.1136/jitc-2020-000908.

  PMID: 32503950 DERIVED

MeSH Terms

Conditions

Carcinoma, Basal Cell; Melanoma; Carcinoma, Merkel Cell

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Prednisone; deltacortene; prednylidene; Tacrolimus

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Adenocarcinoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

The second treatment period where participants received ipilimumab, nivolumab, tacrolimus, and prednisone was optional.

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University/SKCCC

jmurra33@jhmi.edu

4439273568

Study Officials

• Evan J Lipson

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 25, 2019
• Study Start: November 8, 2019
• Primary Completion: October 11, 2022
• Study Completion (Estimated): September 19, 2026
• Last Updated: April 30, 2026
• Results First Posted: June 27, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)