Sarilumab Combined With Ipilimumab, Nivolumab, and Relatlimab in Advanced/Unresectable Melanoma

What is the Purpose of this Study?

This study will evaluate the safety and tolerability of a drug called sarilumab in combination with ipilimumab, nivolumab, and relatlimab in advanced/unresectable melanoma (melanoma that cannot be removed by surgery). Ipilimumab, nivolumab, and relatlimab are immune checkpoint blockers (drugs that block proteins called checkpoints) that have been approved by the U.S. Food and Drug Administration (FDA) as combination ipilimumab/nivolumab and nivolumab/relatlimab for advanced/unresectable melanoma. This phase II study hopes to decrease the toxicity of 3 drugs targeting melanoma with the use of sarilumab. Sarilumab is a monoclonal antibody (type of protein made in a lab). Ipilimumab and nivolumab are also monoclonal antibodies and are approved by the FDA to treat advanced stage III and IV melanomas, but their use in this study is investigational.

Eligibility

* Patients must have signed and dated an Institutional Review Board/Independent Ethics Committee -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 patient care
* Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
* All patients must be either Stage IIIb/c/d or Stage IV according to the American Joint Committee on Cancer (AJCC) (8th edition) and have histologically-confirmed melanoma that is felt to be surgically unresectable in order to be eligible. Please refer to the AJCC Cancer Staging Manual, 8th edition for a description of tumor, lymph node, metastasis and staging.

Inclusion Criteria:

* Patients must have signed and dated an Institutional Review Board/Independent Ethics Committee -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 patient care
* Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
* All patients must be either Stage IIIb/c/d or Stage IV according to the American Joint Committee on Cancer (AJCC) (8th edition) and have histologically-confirmed melanoma that is felt to be surgically unresectable in order to be eligible. Please refer to the AJCC Cancer Staging Manual, 8th edition for a description of tumor, lymph node, metastasis and staging.
* All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible.
* Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical).
oExceptions: Surgery for melanoma and/or post-resection brain radiotherapy (RT) if central nervous system (CNS) metastases and local radiation for locoregional disease and/or prior treatment with adjuvant nivolumab, dabrafenib and trametinib, pembrolizumab, interferon (IFN) or ipilimumab (IPI) (as described in Exclusion Criterion 8,4 full protocol below).
* All patients must have their disease status documented by a complete physical examination and imaging studies within 4 weeks prior to the first dose of study drug. Imaging studies must include computerized tomography (CT) scan of chest, abdomen, pelvis, and all known sites of resected disease in the setting of Stage IIIb/c/d or Stage IV disease, and brain magnetic resonance imaging (\[MRI\]; brain CT is allowable if MRI is contraindicated).
* Disease must be measurable by RECIST 1.1
* The complete set of baseline radiographic images must be available before treatment initiation.

Exclusion Criteria:

* Patients with untreated brain metastases, carcinomatosis meningitis or current ocular/uveal melanoma are excluded.
* Patients with previous non-melanoma malignancies are excluded unless a complete resection or remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include, but are not limited to, non-melanoma skin cancers, in situ bladder cancer, in situ gastric cancer or gastrointestinal stromal tumor, in situ colon cancers, in situ cervical cancers/dysplasia, or breast carcinoma in situ).
* Patients with active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.
* Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease

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Where can I participate?

CS Cancer at The Angeles Clinic and Research Institute : Saba Mukarram

More about this Clinical Trial

What is the full name of this clinical trial?

EIIT2022-S22-00325: A Phase II Study of the Interleukin-6 Receptor Blocking Antibody Sarilumab in Combination with Ipilimumab, Nivolumab and Relatlimab in Patients with Unresectable Stage III or Stage IV Melanoma

Study Details

Disease Type/Condition

Melanoma

Principal Investigator

Mehmi, Inderjit

Co-Investigators

Ani Balmanoukian, Cathie T Chung, Iryna Singh, Justin Moyers, Kristopher Wentzel, Navid Hafez, Omid Hamid, Vi K. Chiu

Age Group

Adult

Phase

IRB Number

STUDY00002449

ClinicalTrials.gov ID

NCT05428007

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Saba Mukarram

Phone

+1 310-231-2181

MukarramS@cshs.org