Drug intelligence / Profile preview

ipilimumab + dasatinib

Development stage
Unknown
Lead developer
Bristol Myers Squibb
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

**Ipilimumab + dasatinib** is an experimental combination therapy composed of two distinct pharmaceuticals: ipilimumab, a monoclonal antibody immune checkpoint inhibitor targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and dasatinib, a small molecule tyrosine kinase inhibitor targeting multiple kinases including KIT, BCR-ABL, and others. The combination has been clinically studied for use in patients with advanced gastrointestinal stromal tumor (GIST) and sarcomas refractory to other therapies. The rationale is to combine immune checkpoint blockade with inhibition of oncogenic kinases to elicit a synergistic antitumor response; however, in early phase Ib trials, while the combination was deemed safe with an acceptable toxicity profile, there was limited clinical efficacy and no evidence of synergistic activity between the two drugs in these cancer types. Elevated absolute lymphocyte count was observed, and correlative analysis suggested that suppression of indoleamine-2,3-dioxygenase (IDO) might be associated with antitumor activity in GIST, though this is a hypothesis-generating finding needing further validation[1].

02

Targets

ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)KIT (c-KIT proto-oncogene receptor tyrosine kinase)EPH (EPH receptor family)SFK (SRC family kinases)PDGFR (PDGFR family)CTLA-4 (Cytotoxic t-lymphocyte–associated protein 4)

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