Phase 1 Study of the Administration of Ipilimumab Intra-Lymphatically Using the Sofusa® DoseConnect™ DEVICE With Nivolumab Administered IV in Patients With Metastatic Melanoma
Overview
- Phase
- Phase 1
- Intervention
- Ipilimumab
- Conditions
- Clinical Stage III Cutaneous Melanoma AJCC v8
- Sponsor
- Mayo Clinic
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) of ipilimumab administration via the DoseConnect device in combination with nivolumab
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This phase I trial identifies the best dose of ipilimumab that can be administered through the DoseConnect™ device followed by nivolumab in treating patients with stage III melanoma that cannot be removed by surgery (unresectable) or stage IV melanoma that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of ipilimumab that can be administered through the DoseConnect™ device followed 30 minutes later by nivolumab intravenously (IV) on day 1 of a 21-day cycle in patients with metastatic melanoma. (Cohort A) II. To determine the maximum tolerated dose (MTD) of ipilimumab that can be administered through up to four (4) DoseConnect™ devices, followed by nivolumab IV on Day 1 of four 21-day cycle in patients with metastatic melanoma. (Cohort B) SECONDARY OBJECTIVE: I. To assess the pharmacokinetics of ipilimumab administered using the DoseConnect™ followed by nivolumab IV in patients with metastatic melanoma. (Cohort A) II. To assess the rate of Grade 3 and 4 adverse events, as well as the rate of drug discontinuation for adverse events and objective response rate (ORR) for patients who receive ipilimumab via the DoseConnect™ device for four cycles in combination with nivolumab administered as an IV infusion, without any IV administration of ipilimumab. (Cohort B) CORRELATIVE OBJECTIVE: I. To assess the changes in immunologic profile after one cycle of ipilimumab administered using the DoseConnect™ followed by nivolumab IV. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive ipilimumab intra-lymphatically via DoseConnect™ on day 1 of cycle 1 and IV over 30 minutes on day 1 of cycles 2-4. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo lymphatic imaging with indocyanine green (ICG) prior to treatment start and blood sample collection throughout the study. (CLOSED TO ENROLLMENT) COHORT B: Patients receive ipilimumab intra-lymphatically via DoseConnect™ and nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study and may optionally undergo lymphatic imaging with ICG prior to treatment start. After completion of study treatment, patients are followed up every 4 months until disease progression, and then every 6 months for up to 2 years after registration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>=18 years
- •Measurable disease as defined below:
- •A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as \>= 2.0 cm with chest x-ray, or as \>= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI)
- •A superficial non-nodal lesion is measurable if its longest diameter is \>= 1.0 cm in diameter as assessed using calipers (e.g., skin nodules) or imaging. In the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended.
- •A malignant lymph node is considered measurable if its short axis is \> 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).
- •NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease.
- •Histologically or cytologically confirmed diagnosis of unresectable stage III or IV metastatic melanoma, meeting one of the following criteria:
- •Progressed after at least one line of FDA approved therapy \[either immune checkpoint inhibitor (ICI) or targeted therapy\]
- •Recurrent disease following initial surgical resection (may or may not have received adjuvant therapy)
- •Newly diagnosed or recurrent in-transit metastatic melanoma (may or may not be treatment naïve)
Exclusion Criteria
- •Metastatic sites that drain lymphatic fluid into nodal beds which are not amenable to lymphatic infusion
- •Sites of metastases limited only to the head and neck
- •Sites of metastatic disease limited to the lungs and/or hilar lymph nodes
- •Metastatic uveal melanoma
- •Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential who are unwilling to employ adequate contraception
- •Persons expecting to conceive or father children during the study or within 180 days (6 months) after the last treatment on this study
- •Active central nervous system (CNS) metastases not previously treated
Arms & Interventions
Cohort A (ipilimumab DC and IV, nivolumab) CLOSED
Patients receive ipilimumab intra-lymphatically via DoseConnect™ on day 1 of cycle 1 and IV over 30 minutes on day 1 of cycles 2-4. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo lymphatic imaging with ICG prior to treatment start and blood sample collection throughout the study. (CLOSED TO ENROLLMENT)
Intervention: Ipilimumab
Cohort A (ipilimumab DC and IV, nivolumab) CLOSED
Patients receive ipilimumab intra-lymphatically via DoseConnect™ on day 1 of cycle 1 and IV over 30 minutes on day 1 of cycles 2-4. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo lymphatic imaging with ICG prior to treatment start and blood sample collection throughout the study. (CLOSED TO ENROLLMENT)
Intervention: Nivolumab
Cohort A (ipilimumab DC and IV, nivolumab) CLOSED
Patients receive ipilimumab intra-lymphatically via DoseConnect™ on day 1 of cycle 1 and IV over 30 minutes on day 1 of cycles 2-4. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo lymphatic imaging with ICG prior to treatment start and blood sample collection throughout the study. (CLOSED TO ENROLLMENT)
Intervention: Lymph Node Assessment
Cohort A (ipilimumab DC and IV, nivolumab) CLOSED
Patients receive ipilimumab intra-lymphatically via DoseConnect™ on day 1 of cycle 1 and IV over 30 minutes on day 1 of cycles 2-4. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo lymphatic imaging with ICG prior to treatment start and blood sample collection throughout the study. (CLOSED TO ENROLLMENT)
Intervention: Biospecimen Collection
Cohort B (Ipilimumab DC and nivolumab IV)
Patients receive ipilimumab intra-lymphatically via DoseConnect™ and nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study and may optionally undergo lymphatic imaging with ICG prior to treatment start.
Intervention: Ipilimumab
Cohort B (Ipilimumab DC and nivolumab IV)
Patients receive ipilimumab intra-lymphatically via DoseConnect™ and nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study and may optionally undergo lymphatic imaging with ICG prior to treatment start.
Intervention: Nivolumab
Cohort B (Ipilimumab DC and nivolumab IV)
Patients receive ipilimumab intra-lymphatically via DoseConnect™ and nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study and may optionally undergo lymphatic imaging with ICG prior to treatment start.
Intervention: Lymph Node Assessment
Cohort B (Ipilimumab DC and nivolumab IV)
Patients receive ipilimumab intra-lymphatically via DoseConnect™ and nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study and may optionally undergo lymphatic imaging with ICG prior to treatment start.
Intervention: Biospecimen Collection
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) of ipilimumab administration via the DoseConnect device in combination with nivolumab
Time Frame: Up to 21 days
MTD is defined as the dose level where at most 1 of the 6 patients treated at that dose level develops a dose-limited event (DLE) during the first cycle of treatment and neither a Grade 3 or worse adverse event (AE) attributable to either drug or device or a Grade 2 or worse AE lasting ≥1 week and attributable to device reported after the first cycle of treatment.
Incidence of adverse events
Time Frame: Up to 21 days
The maximum grade of each type of adverse event will be recorded for each patient. For each adverse event reported by dose level, the percentage of patients developing any degree of that adverse event as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.
Progression-free survival
Time Frame: Up to 2 years
Defined as the time from study entry to the documentation of disease progression.
Overall survival
Time Frame: Up to 2 years
Defined as the time from study entry to death.