Phase 1
N=127
Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
Malignant Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT01024231 ↗Enrolled (actual)
127
Serious AEs
66.9%
Results posted
Mar 2021
Primary outcome: Primary: Number of Participants With an Adverse Event (AE) — 14; 17; 16; 6 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- BMS-936558 (MDX1106-04) (Drug); Ipilimumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Feb 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With an Adverse Event (AE) |
14; 17; 16; 6; 53; 17 | — |
| PRIMARY Number of Participants With a Serious Adverse Event (AE) |
10; 15; 10; 5; 40; 9 | — |
| PRIMARY Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation |
2; 8; 5; 1; 16; 5 | — |
| PRIMARY Number of Deaths |
8; 4; 2; 0; 14; 7 | — |
| PRIMARY Number of Participants With Select AEs |
2; 5; 3; 3; 13; 4 | — |
| PRIMARY Laboratory Abnormalities: Specific Liver Tests |
1; 0; 2; 3; 6; 0 | — |
| PRIMARY Laboratory Abnormalities: Specific Thyroid Tests |
7; 9; 7; 3; 26; 4 | — |
| SECONDARY Objective Response Rate |
21; 47; 50; 50; 42; 53 | — |
| SECONDARY Time to Response |
11.9; 11.9; 11.9; 12.3; 11.9; 8 | — |
| SECONDARY Duration of Response |
NA; 105; 66.3; 59.1; 105; 73.1 | — |
| SECONDARY Progression Free Survival |
12.50; 64.40; 58.40; 33.55; 24.60; 12.15 | — |
| SECONDARY Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) |
1; 1; 2; 0; 4; 1 | — |
| SECONDARY Peak and Trough Concentrations |
6.5; 21.5; 49.8; 63.4; 20.5; 97.7 | — |
Summary
The purpose of this study is to determine the safety and tolerability of treatment with BMS-936558 (MDX-1106) in combination with Ipilimumab (BMS-734016) when given at the same time or as a sequenced regimen in subjects with unresectable Stage III or Stage IV malignant melanoma (MEL)
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria
- Histologic diagnosis of malignant melanoma (MEL)
- Measurable unresectable Stage III or IV MEL
- ECOG performance status score of 0 or 1
- Life expectancy ≥4 months
- For those enrolled in amendment 5 and later, tumor tissue (archival or recent acquisition) must be available
- For Cohorts 1-5, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma not including any post-incisional adjuvant therapy. Subjects may be treatment naïve. All metastatic melanoma regardless of primary site of disease will be allowed
- For Cohorts 6-7, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma; this does not include any post-incisional adjuvant therapy. Specifically, subjects must have received ≥3 doses of Ipilimumab therapy and the last dose having been administered within 4-12 weeks of initiation of study treatment
Exclusion Criteria
- History of severe hypersensitivity reactions to other mAbs
- Prior malignancy active within the previous 2 years except for localized cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence
- Active autoimmune disease or a history of known or suspected autoimmune disease
- History of recently active diverticulitis or symptomatic peptic ulcer disease and history of adrenal insufficiency
- Regular narcotic analgesia
- Active, untreated central nervous system metastasis
- For subjects enrolled in Cohorts 1-5, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody
- For subjects enrolled in Cohorts 6-7, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD137 antibodies
- Any non-oncology vaccine therapy used for prevention of infectious disease
- Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs
- Positive tests for human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), hepatitis B, hepatitis C
- Subjects weighing ≥125 kg are excluded from Cohort 5
- Subjects in Cohorts 6 and 7 must have received Ipilimumab monotherapy immediately prior to study entry, but must not have received that Ipilimumab as part of a clinical trial
- Subjects with ocular melanoma are excluded from Cohort 8
Data sourced from ClinicalTrials.gov (NCT01024231). 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.