Study of Ipilimumab, Nivolumab, and Cabozantinib in Patients With Cutaneous Melanoma

NCT05200143 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2021000533
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this clinical trial is to evaluate the clinical efficacy and progression free survival of the triplet combination of ipilimumab + nivolumab + cabozantinib in patients with anti-PD-1/PD-L1 refractory metastatic cutaneous melanoma.

Conditions

Refractory Cutaneous Melanoma

Keywords

Phase 2; Melanoma; ipilimumab; nivolumab; cabozantinib; anti-pd-1

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival of the Triplet Combination of Ipilimumab + Nivolumab + Cabozantinib in Patients With Anti-PD-1/PD-L1 Refractory Metastatic Cutaneous Melanoma

  Progression free survival (PFS) will be defined as the time between the date of enrollment and the first date of documented progression (per iRECIST), as determined by the investigator, or death due to any cause, whichever occurs first.

  7 Months

Secondary Outcomes (2)

• Safety/Tolerability (CTCAE v5.0)

  13 Months

• Overall Survival

  12 Months

Study Arms (1)

Cabozantinib + Ipilimumab + Nivolumab

EXPERIMENTAL

Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg IV every 3 weeks + Cabozantinib 40 mg PO daily for 4 cycles followed by Nivolumab 480 mg IV every 4 weeks + Cabozantinib 40 mg PO daily for up to 24 months.

Drug: Ipilimumab; Drug: Nivolumab; Drug: Cabozantinib

Interventions

Ipilimumab DRUG

Ipilimumab is a fully human IgG1 kappa monoclonal antibody that binds the co-inhibitory receptor CTLA-4. Antibody binding prevents interaction with the CTLA-4 ligands CD80 and CD86. Blockade of CTLA-4 results in increased T cell activation and proliferation. Ipilimumab was the first immune checkpoint inhibitor to receive FDA approval as a cancer therapy. Treatment of patients with advanced metastatic melanoma with ipilimumab monotherapy resulted in improved overall survival. Subsequent clinical trials with ipilimumab alone and in combination with anti-PD-1 antibodies have demonstrated impressive clinical activity in patients with melanoma, renal cell carcinoma, non-small cell lung cancer and other cancers. Side effects of ipilimumab result from autoimmune attack on healthy tissues. Side effects may include dermatitis, colitis, hepatitis, hypophysitis, pneumonitis, endocrinopathies, nephritis, arthritis, neuropathies and others.

Cabozantinib + Ipilimumab + Nivolumab

Nivolumab DRUG

Nivolumab is a fully human IgG4 kappa monoclonal antibody that binds the co-inhibitory receptor PD-1. Nivolumab binding to PD-1 blocks interaction with the PD-1 ligands PD-L1 and PD-L2. PD-1 blockade can lead to reinvigoration of exhausted T cells and prevent T cell exhaustion of newly activated T cells. Nivolumab has been shown to have excellent clinical efficacy in treating a wide range of cancers as monotherapy and in combination with ipilimumab.

Also known as: BMS-936558, MDX1106, ONO-4538

Cabozantinib + Ipilimumab + Nivolumab

Cabozantinib DRUG

Cabozantinib is a potent small molecule inhibitor of multiple receptor tyrosine kinases. Cabozantinib inhibits VEGFR2, MER, KIT, and MET at single digit nanomolar IC50 concentrations. Other kinases including ROS1, RET, FLT3, RON, AXL, and TIE2 are also inhibited with nanomolar concentrations of cabozantinib. Cabozantinib has been shown to have clinical activity in a variety of solid tumors and has been approved by the FDA for treatment of medullary thyroid cancer, renal cell carcinoma and hepatocellular carcinoma.

Also known as: XL184

Cabozantinib + Ipilimumab + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Histologically (or cytologically) confirmed diagnosis of metastatic cutaneous melanoma.
• Prior therapy:
• Must have been treated previously with an immune checkpoint inhibitor targeting PD-1 or PD-L1.
• Disease progression following treatment with prior anti-PD-1/PD-L1 therapy must be confirmed at least 4 weeks after the first imaging showing disease progression to rule out pseudoprogression.
• Prior therapy with BRAF/MEK inhibitors (before or after anti-PD-1(L1) therapy) is allowed but not required.
• Patients who develop unresectable/metastatic disease while receiving or following completion of adjuvant systemic anti-PD-1/PD-L1 therapy are eligible.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Men and women, aged ≥ 18 years
• Measurable disease meeting the following iRECIST criteria:
• At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or \>1.5 cm in the short-axis diameter for a lymph node metastasis that is serially measurable according to iRECIST using computed tomography/magnetic resonance imaging (CT/MRI).
• Lesions that have had external beam radiotherapy must show evidence of disease progression to qualify as a target lesion.
• ECOG performance status ≤ 1
• Adequate cardiac function, as defined by:
• Left ventricular ejection fraction (LVEF) ≥ 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram,
• Baseline QTc interval ≤ 480 ms

You may not qualify if:

• Prior therapy:
• Prior systemic therapy within 2 weeks of cycle 1 day 1
• Prior therapy with a VEGF(R) inhibitor alone or in combination with immune checkpoint inhibitor(s).
• Prior therapy with an anti-CTLA-4 antibody
• Participants with active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
• Participants 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.
• History of allergy or hypersensitivity to any monoclonal antibody
• Previous or concurrent malignancy within 3 years of study entry, with the following exceptions:
• adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; OR
• other solid tumors treated curatively in which the expected rate of recurrence within 5 years is \< 5%.
• Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) \<6 months prior to screening,
• Symptomatic congestive heart failure (i.e. Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality \<6 months prior to screening. Exceptions include asymptomatic/well-controlled atrial fibrillation/flutter or paroxysmal supraventricular tachycardia;
• Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, despite medical therapy
• History of thromboembolic or cerebrovascular events ≤ 6 months prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e., massive or sub-massive) deep vein thrombosis or pulmonary emboli.

Sponsors & Collaborators

• Providence Health & Services: lead
• Bristol-Myers Squibb: collaborator
• Exelixis: collaborator

Study Sites (1)

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab; cabozantinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Matthew Taylor
• Organization: Providence Portland Medical Center

canrsrchstudies@providence.org

503-215-1979

Study Officials

• Matthew Taylor, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: January 20, 2022
• Study Start: June 8, 2022
• Primary Completion: September 11, 2023
• Study Completion: July 23, 2024
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (1)