Interleukin-6 Receptor Inhibitor Sarilumab in Combination With Ipilimumab, Nivolumab and Relatlimab in Patients With Unresectable Stage III or Stage IV Melanoma

NYU Langone Health

Status and phase: Enrolling; Phase 2

Conditions: Melanoma; Unresectable Melanoma

Treatments: Drug: Nivolumab/Relatlimab; Drug: Sarilumab; Drug: Ipilimumab Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT05428007

22-00325

Details and patient eligibility

About

The study will evaluate how safe the study drug is, how well you tolerate it, and how it works in the body and the disease's response to the drug. The study drug being tested is sarilumab, when given with the combination of ipilimumab, nivolumab, and relatlimab in patients with stage III or stage IV melanoma that cannot be removed by surgery. Previous studies have provided a strong rationale for combining sarilumab, with ipilimumab, nivolumab and relatlimab in metastatic melanoma to reduce side effects and potentially work better for this type of cancer. Sarilumab is an FDA-approved inhibitor of the receptor for the cytokine IL-6, currently approved for the treatment of rheumatoid arthritis, but it is not FDA-approved to treat melanoma. This means that the use of Sarilumab to treat melanoma is considered investigational. The other drugs which will be administered in this study, ipilimumab and nivolumab, are also monoclonal antibodies, but they target different proteins. Ipilimumab and nivolumab are both approved by the FDA to treat advanced stage III and IV melanomas. The nivolumab + relatlimab FDC (fixed dose combination) being used in this study is considered investigational, meaning it is not approved by the FDA.

Full description

In this Phase II, open-label study, the treatment period will consist of an induction phase and a maintenance phase. The induction phase consists of an induction treatment cycle of 8 weeks which is the DLT period. The maintenance phase consists of treatment cycles of 56 days (8 weeks) each, and may extend up to 2 years. During the induction phase, ipilimumab will be administered on day 1 at a dose of 1 mg/kg intravenously (IV) during the 8-week induction period, concurrent with nivolumab 480 mg/relatlimab at 160 mg, fixed dose, administered at a 4 week interval on days 1 and 29 with a 30 minute rest period between the two infusions on day 1 and 29. On days administered in combination, nivolumab/relatlimab will be administered first at a dose of 480 mg/160 mg, followed by ipilimumab at 1 mg/kg, and immediately followed by sarilumab at 150 mg given subcutaneously. Nivolumab/relatlimab and ipilimumab will be each administered IV over 30 minutes consecutively with a 30-minute rest period between infusions, on day 1 of the first and all subsequent 56-day maintenance treatment cycles and nivolumab/relatlimab will be administered on day 29 of each cycle. Sarilumab will be administered subcutaneously every 2 weeks during the 56-day induction treatment cycle and the first two 56-day maintenance cycles only for a total of 24 weeks

Enrollment: 69 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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69 participants in 1 patient group

Study Group

Experimental group

Description:

Participants receive sarilumab at 150 mg flat dose is administered subcutaneously every 2 weeks for 12 doses from day 1, cycle 1 in combination with a regimen of ipilimumab at 1 mg/kg every 8 weeks and fixed dose nivolumab at 480 mg and relatlimab at 160 mg flat dose every 4 weeks two times during the 8-week induction period, then the same regimen again up to week 16, and up to week 24 in maintenance. After week 24 the regimen will be ipilimumab at 1 mg/kg every 8 weeks and fixed dose nivolumab at 480 mg with relatlimab at 160 mg flat dose every 4 weeks for 8 week cycles for up to a total of 2 years in patients with unresectable Stage III/Stage IV melanoma.

Treatment:

Drug: Ipilimumab Injection

Drug: Sarilumab

Drug: Nivolumab/Relatlimab