Phase 3
N=676
MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma
Melanoma · Metastases
Bottom Line
View on ClinicalTrials.gov: NCT00094653 ↗Enrolled (actual)
676
Serious AEs
40.8%
Results posted
Jun 2011
Primary outcome: Primary: Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone — 9.95; 6.44 months — p=0.0004
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- MDX-010 (anti-CTLA4) monoclonal antibody (Drug); MDX-1379 (gp100) Melanoma Peptide Vaccine (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Aug 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone |
9.95; 6.44 | 0.0004 sig |
| SECONDARY Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy |
9.95; 10.12; 6.44 | 0.0026 sig |
| SECONDARY 12-, 18-, and 24-Month Survival Rates |
0.436; 0.456; 0.253; 0.300; 0.332; 0.163 | — |
| SECONDARY Progression Free Survival (PFS) |
2.76; 2.86; 2.76 | — |
| SECONDARY Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24 |
0.491; 0.577; 0.485; 0.164; 0.240; 0.100 | — |
| SECONDARY Time to Progression (TTP) |
2.76; 2.86; 2.76 | — |
| SECONDARY Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD) |
1; 2; 0; 22; 13; 2 | — |
| SECONDARY Determination of Best Overall Response Rate (BORR) |
5.7; 10.9; 1.5 | 0.0433 sig |
| SECONDARY Time to Response |
3.324; 3.176; 2.743 | — |
| SECONDARY Duration of Response |
11.47; NA; NA | — |
| SECONDARY Disease Control Rate (DCR) |
20.1; 28.5; 11.0 | 0.0179 sig |
| SECONDARY Delayed Response (Response Beyond Week 24) |
1; 3; 0; 3; 2; 0 | — |
| SECONDARY Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12 |
-7.4; -8.8; -10.4; -6.2; -5.1; -10.1 | 0.2805 |
| SECONDARY Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death |
98.4; 96.9; 97.0; 50.8; 55.0; 52.3 | — |
| SECONDARY Percentage of Participants With Immune-Related Adverse Events (irAEs) |
58.2; 61.1; 31.8; 11.3; 15.3; 3.0 | — |
| SECONDARY Percentage of Participants With Worst On-Study Hematological Abnormalities |
48.9; 44.6; 46.8; 37.2; 40.5; 34.1 | — |
| SECONDARY Percentage of Participants With Worst On-Study Liver Abnormalities |
83.2; 76.0; 84.9; 13.6; 19.0; 12.7 | — |
| SECONDARY Percentage of Participants With Worst On-Study Renal Abnormalities |
89.5; 88.4; 88.3; 8.8; 9.9; 9.4 | — |
| SECONDARY Clinically Meaningful Changes in Vital Signs and Physical Examinations |
0; 0; 0; 0; 0; 0 | — |
Summary
The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response [PR/CR]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.
Eligibility Criteria
Inclusion Criteria
- Diagnosed with malignant melanoma
- Measurable unresectable Stage III or IV melanoma
- HLA-A*0201 positive
- Previous treatment with & failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
- At least 4 weeks since prior treatment
- Negative pregnancy
- Life expectancy greater than 4 months
- Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
- Required lab values
- Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative
Exclusion Criteria
- Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
- Ocular melanoma
- Active, untreated central nervous system (CNS) metastasis
- Prior treatment with MDX-010 (anti-CTLA4) antibody
- Prior treatment with any cancer therapeutic vaccine
- Active autoimmune disease or history of autoimmune disease
- Pregnancy or nursing
- Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
- Underlying medical conditions deemed hazardous if treated with study drug
- Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
- Unable to provide informed consent
Data sourced from ClinicalTrials.gov (NCT00094653). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.