Intraocular Melanoma, Melanoma (Skin)
Conditions
Keywords
stage III melanoma, stage IV melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, recurrent melanoma, recurrent intraocular melanoma, metastatic intraocular melanoma
Brief summary
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Giving monoclonal antibody therapy together with vaccine therapy may be an effective treatment for stage III or stage IV melanoma. PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with vaccine therapy works in treating patients with resected stage III or stage IV melanoma.
Detailed description
OBJECTIVES: Primary * Achieve at least a 40% autoimmune breakthrough event rate, as defined by the induction of grade 1, grade 2, or acceptable grade 3 drug-related autoimmune adverse events, in patients with resected stage III or IV melanoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51. Secondary * Determine the incidence of drug-related autoimmune adverse events of any grade in patients treated with this regimen. * Determine the time to disease relapse in patients treated with this regimen. * Determine the immunologic response in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1 of weeks 1, 9, 17, 25, 33, 41, and 53 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51 subcutaneously on day 1 of weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, and 53. Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Interventions
BIOLOGICALipilimumab
IV over 90 mins on day 1, wks 1,9,17,25,33,41,53 Dose: 3 mg/kg (Part I), 10 mg/kg (Part II)
BIOLOGICALTyrosinase/gp100/MART-1 Peptides
(All subjects in Part I and HLA-A\*0201 positive subjects only in Part II): SC, day 1 of wks 1,3,5,7,9,11,17, 21,25,33,41,53 Dose: 1 mg peptide emulsified in 1 mL Montanide ISA 51 VG.)
Sponsors
National Cancer Institute (NCI)
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed melanoma * Stage III (≥ 3 positive lymph nodes) or stage IV disease * Mucosal or ocular melanoma allowed * Completely resected within the past 6 months * Patients with stage III resected melanoma rendered free of disease may have failed, been ineligible for, or refused prior treatment with interferon alfa * Positive staining of tumor tissue for at least one of the following: * Antibody HMB-45 for gp100 * Antibody HMB-45 for tyrosinase * Antibody HMB-45 for MART-1 * HLA-A\*0201 positive by DNA allele-specific polymerase chain reaction assay PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * At least 6 months Hematopoietic * WBC ≥ 2,500/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hematocrit ≥ 30% * Hemoglobin ≥ 10 g/dL Hepatic * AST ≤ 3 times upper limit of normal (ULN)\* * Bilirubin ≤ ULN\* (\< 3.0 mg/dL for patients with Gilbert's syndrome) * No significant hepatic disease that would preclude study participation * Hepatitis B surface antigen negative * Hepatitis C antibody negative NOTE: \* Unless attributable to disease Renal * Creatinine ≤ 2.0 mg/dL * No significant renal disease that would preclude study participation Cardiovascular * No significant cardiac disease that would preclude study participation Pulmonary * No significant pulmonary disease that would preclude study participation Immunologic * No history of any of the following: * Inflammatory bowel disease or any other autoimmune bowel disease * Systemic lupus erythematosus * Rheumatoid arthritis * Autoimmune ocular disease * No systemic hypersensitivity to Montanide ISA-51 or any vaccine component * No active infection requiring therapy * HIV negative Other * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix * No significant gastrointestinal disease that would preclude study participation * No significant psychiatric disease that would preclude study participation * No other medical condition that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 4 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) * No prior gp100 antigen, MART-1 antigen, or tyrosinase peptide * At least 4 weeks since prior immunotherapy for melanoma and recovered * No other concurrent immunotherapy Chemotherapy * At least 4 weeks since prior chemotherapy for melanoma (6 weeks for nitrosoureas) and recovered * No concurrent chemotherapy Endocrine therapy * At least 4 weeks since prior hormonal therapy for melanoma and recovered * At least 4 weeks since prior systemic, inhaled, or topical corticosteroids * No concurrent systemic, inhaled, or topical corticosteroids Radiotherapy * At least 4 weeks since prior radiotherapy for melanoma and recovered Surgery * See Disease Characteristics * At least 4 weeks since prior surgery for melanoma and recovered Other * No concurrent immunosuppressive agents (e.g., cyclosporine and its analog) * Concurrent analgesic therapy allowed provided the dose is stable for the past 14 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Immune-related Adverse Events (irAEs) | Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase) | Percentage of participants who experienced an irAE during the course of the study defined by the induction of Grade 1, Grade 2, or acceptable Grade 3 drug-related irAEs. For the purposes of this trial, acceptable drug-related irAEs are skin-related immune-mediated adverse events \< or = Grade 3 (potentially reversible inflammation \< Grade 4 that can be attributable to a local antitumor reaction that could potentially be a therapeutic response will also be considered an acceptable irAE). Note: The confidence interval was calculated using the Clopper Pearson method |
| Time to Disease Relapse | up to 3 years | To determine the time (months) from first dose to disease relapse. Time to disease relapse is defined from the start of treatment to the first occurrence of any new lesion (reported by the investigator on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma) or death. Participants who neither relapse nor died will be censored on the date of their last tumor evaluation. Median estimated using Kaplan-Meier method; A two-sided 95% CI for median in each treatment group was computed via the log-log transformation method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Hematology-related Lab Abnormalities | Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase) | The number of participants who experienced a Hematology-related laboratory abnormality (grade 1-4 and grade 3-4 categories, grade 4 being the worst) during the course of the study. Laboratory tests were graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. |
| Number of Participants With Drug-related irAEs of Any Grade | Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase) | The number of participants who experienced a drug-related irAE of any grade over the course of the study. Note: The confidence interval was calculated using the Clopper Pearson method |
| Time to Disease Relapse | up to 3 years | To determine the time (months) from first dose to disease relapse. Time to disease relapse is defined from the start of treatment to the first occurrence of any new lesion (reported by the investigator on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma) or death. Participants who neither relapse nor died will be censored on the date of their last tumor evaluation. Median estimated using Kaplan-Meier method; A two-sided 95% CI for median in each treatment group was computed via the log-log transformation method. |
| Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase) | The number of participants who experienced a Serum Chemistry-related laboratory abnormality (grade 1-4 and grade 3-4 categories, grade 4 being the worst) during the course of the study. Laboratory tests were graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. |
| Immunologic Response to the Dose Regimen | up to 3 years | The secondary objective was to determine the immunologic response to the dosing regimen, via Human Anti-Human Antibody (HAHA) Assessment, displayed by number of participants observed as HAHA positive or negative. Note: If participant had at least one post-baseline HAHA result with increase in titer over pre-study, the participant is counted as HAHA Positive. A participant with all negative post-baseline results is counted as HAHA negative. |
Countries
United States
Participant flow
Pre-assignment details
77 participants enrolled, 76 treated. 1 not treated due to protocol violation.
Participants by arm
| Arm | Count |
|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES HLA-A\*201 positive participants receive ipilimumab at 3 mg/kg/dose as an intravenous (i.v.) infusion every 8 weeks for 12 months for a total of 7 infusions.
Peptides administered at Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, and 53 for a total of 12 vaccinations. | 25 |
| 10 MG/KG IPILIMUMAB + PEPTIDES HLA-A\*201 positive participants receive ipilimumab at 10 mg/kg/dose as an intravenous (i.v.) infusion every 8 weeks for 12 months for a total of 7 infusions.
Peptides administered at Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, and 53 for a total of 12 vaccinations. | 25 |
| 10 MG/KG IPILIMUMAB HLA-A\*201 negative participants receive ipilimumab at 10 mg/kg/dose as an intravenous (i.v.) infusion every 8 weeks for 12 months for a total of 7 infusions. | 26 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Disease progression | 9 | 0 | 0 |
| Overall Study | Disease relapse | 0 | 9 | 10 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Other reasons | 0 | 12 | 11 |
| Overall Study | Withdrawal by Subject | 15 | 4 | 4 |
Baseline characteristics
| Characteristic | 3.0 MG/KG IPILIMUMAB + PEPTIDES | 10 MG/KG IPILIMUMAB + PEPTIDES | 10 MG/KG IPILIMUMAB | Total |
|---|---|---|---|---|
| Age, Continuous | 54.7 Years STANDARD_DEVIATION 15.25 | 53.3 Years STANDARD_DEVIATION 10.34 | 51.5 Years STANDARD_DEVIATION 14.06 | 53.1 Years STANDARD_DEVIATION 13.28 |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 25 Participants | 25 Participants | 75 Participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 9 Participants | 31 Participants |
| Sex: Female, Male Male | 13 Participants | 15 Participants | 17 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 25 / 25 | 25 / 25 | 25 / 26 |
| serious Total, serious adverse events | 5 / 25 | 7 / 25 | 10 / 26 |
Outcome results
Primary
Percentage of Participants With Immune-related Adverse Events (irAEs)
Percentage of participants who experienced an irAE during the course of the study defined by the induction of Grade 1, Grade 2, or acceptable Grade 3 drug-related irAEs. For the purposes of this trial, acceptable drug-related irAEs are skin-related immune-mediated adverse events \< or = Grade 3 (potentially reversible inflammation \< Grade 4 that can be attributable to a local antitumor reaction that could potentially be a therapeutic response will also be considered an acceptable irAE). Note: The confidence interval was calculated using the Clopper Pearson method
Time frame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Percentage of Participants With Immune-related Adverse Events (irAEs) | 80.0 Percentage of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Percentage of Participants With Immune-related Adverse Events (irAEs) | 72.0 Percentage of participants |
| 10 MG/KG IPILIMUMAB | Percentage of Participants With Immune-related Adverse Events (irAEs) | 65.4 Percentage of participants |
Primary
Time to Disease Relapse
To determine the time (months) from first dose to disease relapse. Time to disease relapse is defined from the start of treatment to the first occurrence of any new lesion (reported by the investigator on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma) or death. Participants who neither relapse nor died will be censored on the date of their last tumor evaluation. Median estimated using Kaplan-Meier method; A two-sided 95% CI for median in each treatment group was computed via the log-log transformation method.
Time frame: up to 3 years
Population: All treated participants for the 10 mg/kg ipilimumab arms of the study only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Time to Disease Relapse | NA Months |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Time to Disease Relapse | NA Months |
Secondary
Immunologic Response to the Dose Regimen
The secondary objective was to determine the immunologic response to the dosing regimen, via Human Anti-Human Antibody (HAHA) Assessment, displayed by number of participants observed as HAHA positive or negative. Note: If participant had at least one post-baseline HAHA result with increase in titer over pre-study, the participant is counted as HAHA Positive. A participant with all negative post-baseline results is counted as HAHA negative.
Time frame: up to 3 years
Population: All Treated Subjects with Baseline and at Least one Post-Baseline HAHA Assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Immunologic Response to the Dose Regimen | HAHA positive | 5 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Immunologic Response to the Dose Regimen | HAHA positive at baseline | 5 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Immunologic Response to the Dose Regimen | HAHA negative | 19 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Immunologic Response to the Dose Regimen | HAHA positive | 2 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Immunologic Response to the Dose Regimen | HAHA positive at baseline | 1 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Immunologic Response to the Dose Regimen | HAHA negative | 19 Number of participants |
| 10 MG/KG IPILIMUMAB | Immunologic Response to the Dose Regimen | HAHA positive at baseline | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Immunologic Response to the Dose Regimen | HAHA negative | 20 Number of participants |
| 10 MG/KG IPILIMUMAB | Immunologic Response to the Dose Regimen | HAHA positive | 1 Number of participants |
Secondary
Number of Participants Experiencing Hematology-related Lab Abnormalities
The number of participants who experienced a Hematology-related laboratory abnormality (grade 1-4 and grade 3-4 categories, grade 4 being the worst) during the course of the study. Laboratory tests were graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Time frame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | White blood cells, grade 1-4 | 5 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | White blood cells, grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Absolute Neutrophil Count, grade 1-4 | 6 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Absolute Neutrophil Count, grade 3-4 | 1 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Platelet Count, grade 1-4 | 4 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Platelet Count, grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Hemoglobin, grade 1-4 | 8 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Hemoglobin, grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Lymphocytes, grade 1-4 | 19 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Lymphocytes, grade 3-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Lymphocytes, grade 1-4 | 15 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | White blood cells, grade 1-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Platelet Count, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Platelet Count, grade 1-4 | 2 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | White blood cells, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Lymphocytes, grade 3-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Hemoglobin, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Absolute Neutrophil Count, grade 1-4 | 2 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Hemoglobin, grade 1-4 | 10 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Hematology-related Lab Abnormalities | Absolute Neutrophil Count, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Hemoglobin, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Absolute Neutrophil Count, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Platelet Count, grade 1-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Platelet Count, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Lymphocytes, grade 1-4 | 17 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Hemoglobin, grade 1-4 | 15 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | White blood cells, grade 1-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Lymphocytes, grade 3-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | White blood cells, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Hematology-related Lab Abnormalities | Absolute Neutrophil Count, grade 1-4 | 3 Number of participants |
Secondary
Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities
The number of participants who experienced a Serum Chemistry-related laboratory abnormality (grade 1-4 and grade 3-4 categories, grade 4 being the worst) during the course of the study. Laboratory tests were graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Time frame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Lipase, grade 1-4 | 3 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Total Bilirubin, grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | aspartate aminotransferase (AST), grade 1-4 | 9 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Amylase, grade 3-4 | 1 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Alkaline Phosphatase, grade 1-4 | 5 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | alanine aminotransferase (ALT), grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Amylase, grade 1-4 | 5 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Alkaline Phosphatase, grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Lipase, grade 3-4 | 2 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | aspartate aminotransferase (AST), grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Creatinine, grade 3-4 | 0 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | alanine aminotransferase (ALT), grade 1-4 | 5 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Total Bilirubin, grade 1-4 | 2 Number of participants |
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Creatinine, grade 1-4 | 3 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Lipase, grade 1-4 | 5 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | alanine aminotransferase (ALT), grade 1-4 | 6 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | alanine aminotransferase (ALT), grade 3-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | aspartate aminotransferase (AST), grade 1-4 | 4 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | aspartate aminotransferase (AST), grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Total Bilirubin, grade 1-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Total Bilirubin, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Alkaline Phosphatase, grade 1-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Alkaline Phosphatase, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Amylase, grade 1-4 | 7 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Amylase, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Lipase, grade 3-4 | 2 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Creatinine, grade 1-4 | 2 Number of participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Creatinine, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Creatinine, grade 1-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Amylase, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Total Bilirubin, grade 1-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | aspartate aminotransferase (AST), grade 3-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Lipase, grade 1-4 | 10 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | aspartate aminotransferase (AST), grade 1-4 | 7 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | alanine aminotransferase (ALT), grade 1-4 | 7 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Lipase, grade 3-4 | 4 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | alanine aminotransferase (ALT), grade 3-4 | 1 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Alkaline Phosphatase, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Alkaline Phosphatase, grade 1-4 | 3 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Creatinine, grade 3-4 | 0 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Amylase, grade 1-4 | 10 Number of participants |
| 10 MG/KG IPILIMUMAB | Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities | Total Bilirubin, grade 3-4 | 1 Number of participants |
Secondary
Number of Participants With Drug-related irAEs of Any Grade
The number of participants who experienced a drug-related irAE of any grade over the course of the study. Note: The confidence interval was calculated using the Clopper Pearson method
Time frame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants With Drug-related irAEs of Any Grade | 24 Participants |
| 10 MG/KG IPILIMUMAB + PEPTIDES | Number of Participants With Drug-related irAEs of Any Grade | 24 Participants |
| 10 MG/KG IPILIMUMAB | Number of Participants With Drug-related irAEs of Any Grade | 24 Participants |
Secondary
Time to Disease Relapse
To determine the time (months) from first dose to disease relapse. Time to disease relapse is defined from the start of treatment to the first occurrence of any new lesion (reported by the investigator on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma) or death. Participants who neither relapse nor died will be censored on the date of their last tumor evaluation. Median estimated using Kaplan-Meier method; A two-sided 95% CI for median in each treatment group was computed via the log-log transformation method.
Time frame: up to 3 years
Population: All treated participants for the 3 mg/kg ipilimumab arm of the study only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 3.0 MG/KG IPILIMUMAB + PEPTIDES | Time to Disease Relapse | NA Months |