A Phase II, Single-Arm Clinical Trial Evaluating the Triplet Combination of Ipilimumab, Nivolumab, and Cabozantinib in Patients With Anti-PD-1(L1) Refractory Cutaneous Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Refractory Cutaneous Melanoma
- Sponsor
- Providence Health & Services
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Progression Free Survival of the Triplet Combination of Ipilimumab + Nivolumab + Cabozantinib in Patients With Anti-PD-1/PD-L1 Refractory Metastatic Cutaneous Melanoma
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
This is a phase II, single arm, single institution clinical trial. Eligible adults with anti-PD-1 refractory, unresectable/metastatic cutaneous melanoma will be treated with the triplet combination of ipilimumab 1 mg/kg + nivolumab 3 mg/kg every 3 weeks for 4 cycles in addition to cabozantinib 40 mg/day. For cycles 5+, treatment will consist of nivolumab 480 mg IV every 4 weeks in combination with cabozantinib 40 mg/day. The total duration of therapy will be 24 months or until either disease progression or the occurrence of unacceptable drug-related toxicity. Regular tumor assessments should be performed to determine if PD is present.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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-L
- •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).
Exclusion Criteria
- •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%.
Arms & Interventions
Cabozantinib + Ipilimumab + Nivolumab
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.
Intervention: Ipilimumab
Cabozantinib + Ipilimumab + Nivolumab
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.
Intervention: Nivolumab
Cabozantinib + Ipilimumab + Nivolumab
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.
Intervention: Cabozantinib
Outcomes
Primary Outcomes
Progression Free Survival of the Triplet Combination of Ipilimumab + Nivolumab + Cabozantinib in Patients With Anti-PD-1/PD-L1 Refractory Metastatic Cutaneous Melanoma
Time Frame: 7 Months
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.
Secondary Outcomes
- Safety/Tolerability (CTCAE v5.0)(13 Months)
- Overall Survival(12 Months)