PLX9486 was designed to selectively and potently inhibit the KIT D816V mutation. Promising early clinical data in approximately 50 patients support continued clinical development and the potential to address unmet medical needs for patients with advanced GIST. In 2021, Unum plans to advance PLX9486 in patients with systemic mastocytosis (ASM and ISM) and patients with advanced gastrointestinal stromal tumors (GIST).


Systemic Mastocytosis occurs when mast cells inappropriately accumulate in various internal organs, including the bone marrow. In Advanced Systemic Mastocytosis (ASM), organ function can be significantly impaired, and median life-span is significantly reduced to less than approximately 3.5 years . In Indolent Systemic Mastocytosis, patients experience a range of symptoms that have a significant negative impact on quality of life. In both of these conditions, mast cells accumulate to unhealthy levels due to a genetic mutation in the KIT gene. This mutation, D816V, renders the KIT gene permanently active resulting in unchecked proliferation of mast cells. 

People living with Systemic Mastocytosis often experience a range of neurological, gastrointestinal, cutaneous and systemic symptoms, including fatigue, skin redness and warmth (flushing), urticaria pigmentosa, nausea, abdominal pain, bloating, diarrhea, gastroesophageal reflux (GERD), shortness of breath, low blood pressure (hypotension), lightheadedness, and headache. Some people may experience attention or memory problems, anxiety, or depression. Nearly half of individuals with Systemic Mastocytosis will experience severe allergic reactions (anaphylaxis).

Unum’s PLX9486 was designed to selectively inhibit the KIT D816V mutation, and clinical activity and safety as a monotherapy will be investigated in patients with systemic mastocytosis.

Advanced Systemic Mastocytosis: Clinical trials expected to start in 1H 2021

Indolent Systemic Mastocytosis: Clinical trials expected to start in 2H 2021

*Pending FDA interactions

1 Castells MC. Mastocytosis: Moving the Field to Precision and Personalized Medicine. Immunol Allergy Clin North Am. 2018 Aug;38(3):xv-xvii. doi: 10.1016/j.iac.2018.05.001. Epub 2018 Jun 9. Citation on PubMed

2 Scherber RM, Borate U. How we diagnose and treat systemic mastocytosis in adults. Br J Haematol. 2018 Jan;180(1):11-23. doi: 10.1111/bjh.14967. Epub 2017 Oct 19. Review. Citation on PubMed

3 Tremblay D, Carreau N, Kremyanskaya M, Mascarenhas J. Systemic Mastocytosis: Clinical Update and Future Directions. Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):728-38. doi: 10.1016/j.clml.2015.07.644. Epub 2015 Aug 5. Review. Citation on PubMed


Gastrointestinal stromal tumors (GIST) are categorized by uncontrolled cell growth in the tissues of the gastrointestinal tract (GI). 

Advanced GIST tumors have a strong dependence on oncogenic KIT signaling. At diagnosis, approximately 80% of GIST patients carry KIT mutations that drive their tumor growth. Inhibition of these mutations with tyrosine kinase inhibitors (TKIs) markedly improves survival of GIST patients. However, most patients develop resistance, including some driven by mutations in the KIT activation loop.

Unum’s PLX9486 was designed to be a potent and selective KIT D816V inhibitor that precisely targets KIT mutations including activation loop mutations, potentially addressing the unmet medical need for patients with GIST.

  • PLX9486 is highly selective, sparing other kinase targets such as wild-type KIT, PDGFRα, VEGFR2, FLT3, and FMS. 
  • PLX9486 safety has been clinically evaluated in 50+ patients to date, both as a single agent and as part of a combination therapy. 
  • In a Phase 1/2 trial sponsored by Plexxikon, Inc. testing the combination of PLX9486 with sunitinib in 18 patients with advanced GIST, median progression free survival (PFS) reached 11 months. These patients had been heavily treated previously:
    • Almost three-quarters of patients had previously received sunitinib and seen their disease progress.
    • Two-thirds of patients had been treated with three or more TKIs.
    • Half of patients had received more than four TKIs. 

An additional clinical trial in GIST expected to start in 2H 2021.

*Pending FDA interactions

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