Combining Sarilumab with Other Treatments for Advanced Melanoma

A Phase II Study of the Interleukin-6 Receptor Inhibitor Sarilumab in Combination With Ipilimumab, Nivolumab and Relatlimab in Patients With Unresectable Stage III or Stage IV Melanoma

This study is testing a new combination of treatments for people with advanced melanoma to see if it helps them feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 105 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: NYU Langone Health (other)
• Drugs / interventions: nivolumab, pembrolizumab, ipilimumab, trametinib, radiation, prednisone, sarilumab, relatlimab
• Locations: 4 sites (Los Angeles, California and 3 other locations)
• Trial ID: NCT05428007 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the safety and efficacy of sarilumab, an IL-6 receptor inhibitor, in combination with ipilimumab, nivolumab, and relatlimab for patients with unresectable stage III or IV melanoma. The study consists of an induction phase lasting 8 weeks followed by a maintenance phase that may extend up to 2 years. Participants will receive these treatments through intravenous and subcutaneous administration, with careful monitoring of their response and side effects. The goal is to determine how well this combination works in treating advanced melanoma and to assess its tolerability.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically-confirmed unresectable stage III or IV melanoma, excluding ocular/uveal melanoma.

Not a fit: Patients with resectable melanoma or those with ocular/uveal melanoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced melanoma that cannot be surgically removed.

How similar studies have performed: Previous studies have shown promising results with similar combinations of immunotherapies in treating melanoma, suggesting potential for success in this approach.

Eligibility criteria

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

Where this trial is running

Los Angeles, California and 3 other locations

• The Angeles Clinic at Cedars Sinai — Los Angeles, California, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• NYU Langone Health — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Janice Mehnert, MD — NYU Langone Health
• Study coordinator: Janice Mehnert, MD

Conditions: Melanoma, Unresectable Melanoma