Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
A Phase II Study to Assess the Safety and Efficacy of Tocilizumab in Combination With Ipilimumab and Nivolumab in Patients With Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
2 other identifiers
interventional
35
1 country
1
Brief Summary
This phase II trial investigates the side effects of tocilizumab, ipilimumab, and nivolumab in treating patients with melanoma, non-small cell lung cancer, or urothelial carcinoma that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tocilizumab is a monoclonal antibody that may interfere with the immune system to decrease immune-related toxicities. Giving tocilizumab, ipilimumab, and nivolumab may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2021
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2021
CompletedFirst Posted
Study publicly available on registry
June 25, 2021
CompletedStudy Start
First participant enrolled
September 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
March 6, 2026
March 1, 2026
6.3 years
June 18, 2021
March 5, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of dose limiting toxicity
Will be summarized overall and for each tumor type using frequencies and percentages.
Up to 2 years
Occurrence of one or more grade 3 or higher adverse event in a given patient (Cohort 1)
Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Grade 3 or greater toxicity rate will be computed along with their associated exact 95% confidence interval.
Up to 2 years
Secondary Outcomes (3)
Best overall response
Up to 2 years
Progression-free survival (PFS)
Time from the start of treatment to disease progression (defined by irRECIST) or death, whichever occurs first, assessed up to 2 years
Overall survival (OS)
Time from the start of treatment to death from any cause, assessed up to 2 years
Study Arms (3)
Cohort 1 (ipilimumab, nivolumab, tocilizumab)
EXPERIMENTALPatients with melanoma will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses.
Cohort 2 (ipilimumab, nivolumab, tocilizumab)
EXPERIMENTALPatients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity.
Cohort 3 (ipilimumab,, nivolumab, tocilizumab)
EXPERIMENTALPatients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given SC
Eligibility Criteria
You may qualify if:
- \) Signed Written Informed Consent
- Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
- Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, tumor biopsies, and other requirements of the study.
- All consented participants should be registered in the institutional database CORe 2) Type of Participant and Target Disease Characteristics
- Cohort 1:
- Melanoma (n=35 patients)
- Histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) Version 8 staging system (Appendix A). Patients must consent to BRAF testing or have documented BRAF status as per regionally acceptable V600 mutational status testing. Specifically, 10 melanoma patients will be initially enrolled, and an additional 25 melanoma patients will be enrolled in expansion cohort. Patients with biopsiable disease will have tissue collected including patients in the expansion cohorts. Archival tumor tissue samples may be collected in place of the biopsy after PI consultation. If biopsy is not feasible, or the patient declines to participate due to the biopsy, the patient may still enroll with PI approval.
- Treatment-naïve participants (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) with the exception of prior adjuvant treatment for melanoma with approved agents (eg, BRAF/MEK inhibitors, ipilimumab, nivolumab, pembrolizumab or interferon). Participants who have had recurrence within the 6 months of completing adjuvant treatment are not eligible.
- Cohort 2:
- Urothelial Carcinoma (n=10 patients) 1. Histologically or cytologically documented locally advanced or transitional cell carcinoma of the urothelium including renal pelvis, ureters, urinary bladder, or urethra. Patients with mixed histologies are required to have a dominant transitional cell pattern.
- \. Enrollment of urothelial carcinoma 1st line patients who are cisplatin-ineligible and who, after consultation with the investigator, choose to forego front-line chemotherapy or immunotherapy.
- \. Treatment naïve, cisplatin-eligible patients who refuse chemotherapy standard of care or treatment naive, cisplatin-ineligible patients who meet at least one of the following criteria:
- \- Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade ≥ 2 audiometric hearing loss. CTCAE v5 Grade ≥ 2 peripheral neuropathy.
- Cisplatin ineligibility defined as: GFR less than 60 and ≥ 15 mL/min or; CHF NYHA class III or higher or; peripheral neuropathy grade 2 or higher or ECOG PS 2 or higher or; impaired hearing grade 2 or higher.
- GFR is either measured using a 24 hour urine, calculated using Cockroft-Gault, or estimated using the MDRD method from the National Kidney Disease Education Program (NKDEP) (the method reported by MDACC laboratories).
- +22 more criteria
You may not qualify if:
- \) Medical Conditions
- a) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- b) Uveal melanoma is excluded. c) Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the patient from adhering to the protocol or would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results (eg, a condition associated with diarrhea or acute diverticulitis).
- d) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
- e) Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- f) Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of week 0 day 1. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Please see Section 4.3for permitted therapies.
- g) History of organ transplant or tissue that requires systemic use of immune suppressive agents h) Active infection requiring systemic therapy within 14 days prior to week 0 day 1.
- i) Known cardiac history including: i) History of unstable or deteriorating cardiac disease within the previous 12 months prior to screening including but not limited to the following:
- (1) Unstable angina or myocardial infarction (2) Transient ischemic attack (TIA)/Cerebrovascular accident (CVA) (3) Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) (4) Uncontrolled clinically significant arrhythmias j) Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
- \) Prior/Concomitant Therapy
- d) Participants with history of life-threatening toxicity related to prior immune therapy (e.g. anti- CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T- cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (e.g. Hormone replacement after adrenal crisis) e) Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to study treatment initiation.
- \) Physical and Laboratory Test Findings
- WBC \< 2000/μL
- Neutrophils \< 1500/μL
- Platelets \< 100,000/μL
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
Fa'ak F, Buni M, Falohun A, Lu H, Song J, Johnson DH, Zobniw CM, Trinh VA, Awiwi MO, Tahon NH, Elsayes KM, Ludford K, Montazari EJ, Chernis J, Dimitrova M, Sandigursky S, Sparks JA, Abu-Shawer O, Rahma O, Thanarajasingam U, Zeman AM, Talukder R, Singh N, Chung SH, Grivas P, Daher M, Abudayyeh A, Osman I, Weber J, Tayar JH, Suarez-Almazor ME, Abdel-Wahab N, Diab A. Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events. J Immunother Cancer. 2023 Jun;11(6):e006814. doi: 10.1136/jitc-2023-006814.
PMID: 37328287DERIVEDHailemichael Y, Johnson DH, Abdel-Wahab N, Foo WC, Bentebibel SE, Daher M, Haymaker C, Wani K, Saberian C, Ogata D, Kim ST, Nurieva R, Lazar AJ, Abu-Sbeih H, Fa'ak F, Mathew A, Wang Y, Falohun A, Trinh V, Zobniw C, Spillson C, Burks JK, Awiwi M, Elsayes K, Soto LS, Melendez BD, Davies MA, Wargo J, Curry J, Yee C, Lizee G, Singh S, Sharma P, Allison JP, Hwu P, Ekmekcioglu S, Diab A. Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity. Cancer Cell. 2022 May 9;40(5):509-523.e6. doi: 10.1016/j.ccell.2022.04.004. Epub 2022 May 9.
PMID: 35537412DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rodabe Amaria, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 18, 2021
First Posted
June 25, 2021
Study Start
September 23, 2021
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
March 6, 2026
Record last verified: 2026-03