# EXPLORER: safety and efficacy of avapritinib in advanced systemic mastocytosis (phase 1)

Source: https://onco.cc/key-papers/paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021/  
OnCo record `paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first study of avapritinib, a drug designed to hit the KIT D816V mutation that drives most mastocytosis, produced responses in three quarters of patients with advanced disease and set the dose for later trials.

## Summary

Phase 1 dose-escalation and expansion study of 86 patients with advanced systemic mastocytosis treated with avapritinib, a selective inhibitor of KIT D816V.

The overall response rate in response-evaluable patients was 75 percent with deep and durable responses, falls in serum tryptase and KIT D816V allele burden, and a recommended dose of 200 mg daily; cognitive effects and intracranial bleeding (mainly with severe thrombocytopenia) were the notable toxicities. The results, with PATHFINDER, led to approval of avapritinib for advanced systemic mastocytosis in 2021.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: Nature Medicine
- Year: 2021
- DOI: 10.1038/s41591-021-01538-9
- Authors: DeAngelo DJ, Radia DH, George TI, et al.
- Findings: Overall response 75 percent in evaluable patients; complete remissions with full or partial haematological recovery in a substantial minority.; Intracranial haemorrhage occurred mainly in patients with platelet counts below 50,000 per microlitre, prompting a platelet threshold for treatment.
- What it means: Avapritinib is the most active drug in advanced systemic mastocytosis; platelet counts must be checked before and during treatment.
- Caveats: Phase 1 without a comparator; response criteria changed between cohorts.; Cognitive adverse effects are common and dose-related.

## Sources

- Nat Med 2021: https://doi.org/10.1038/s41591-021-01538-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34873347/

## Connected records

- cancers: [Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)](https://onco.cc/cancers/advanced-systemic-mastocytosis/)
- drugs: [Avapritinib](https://onco.cc/drugs/avapritinib/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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