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Center for Global Research Data

Early markers of clinical outcome to ipilimumab therapy for advanced melanoma

Lead Investigator: Michael J. Sorich, Flinders University of South Australia
Title of Proposal Research: Early markers of clinical outcome to ipilimumab therapy for advanced melanoma
Vivli Data Request: 7140
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Immune checkpoint inhibitors (ICIs) represent a very important recent development in the treatment of advanced melanoma. Notably, a subset of patients responds very well to ipilimumab, a types ofICI treatment, and this subset have significantly improved survival. The ability to predict in advance the individuals who are unlikely to benefit is likely to be valuable for guiding decisions regarding the duration and choice of therapy. A number of small studies suggest that early changes in absolute lymphocyte count (ALC), absolute eosinophil count (AEC) and serum lactate dehydrogenase (LDH) may predict response and survival for individuals using ipilimumab (Ku 2010, Delyon 2013, Simeone 2014). However, the smalI sample size and differences in methods and reporting limit the ability to evaluate the validity and comparative performance of these markers. These are also very preliminary evidence that LDH and ALC changes may also be of value for a different type of ICI therapy – PDI inhibitors (Martens 2016, Diem 2016). A small study has also suggesting that changes in AEC may predict risk of immune related adverse events (Schindler 2014). A larger and more comprehensive evaluation of the validity and nature of these associations is required before clinical use of such markers may be realistically considered.

The research proposed will utilise data from studies of ipilimumab therapy for advanced melanoma to evaluate whether early (week 6) changes in selected putative laboratory markers are associated with subsequent response, toxicity and survival. The association will be primarily evaluated by Cox proportional hazards regression for survival outcomes and logistic regression for best overall response and toxicity. Results will be communicated via publication in a peer-reviewed international cancer scientific journal and presented at scientific conferences.

Study Design: Retrospective secondary cohort analysis of relevant participants in existing clinical studies.

Requested Studies:

MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma
Data Contributor: Bristol Myers Squibb
Study ID: NCT00094653
Sponsor ID: CA184-002

Phase II Study to Determine Predictive Markers of Response to BMS-734016 (MDX-010)
Data Contributor: Bristol Myers Squibb
Study ID: NCT00261365
Sponsor ID: CA184-004

A Study of MDX-010 (BMS-734016) Administered With or Without Prophylactic Oral Budesonide
Data Contributor: Bristol Myers Squibb
Study ID: NCT00135408
Sponsor ID: CA184-007

A Single Arm Study of Ipilimumab Monotherapy in Patients With Previously Treated Unresectable Stage III or IV Melanoma
Data Contributor: Bristol Myers Squibb
Study ID: NCT00289627
Sponsor ID: CA184-008

Monoclonal Antibody With or Without gp100 Peptides Plus Montanide ISA-51 in Treating Patients With Stage IV Melanoma
Data Contributor: Bristol Myers Squibb
Study ID: NCT00077532
Sponsor ID: CA184-021

Study of Ipilimumab (MDX-010) Monotherapy in Patients With Previously Treated Unresectable Stage III or IV Melanoma
Data Contributor: Bristol Myers Squibb
Study ID: NCT00289640
Sponsor ID: CA184-022

Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma
Data Contributor: Bristol Myers Squibb
Study ID: NCT00324155
Sponsor ID: CA184-024

Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases
Data Contributor: Bristol Myers Squibb
Study ID: NCT00623766
Sponsor ID: CA184-042