AYVAKYT was evaluated in the largest ever trial of patients with ISM1,2
PIONEER is an ongoing 3-part, randomised, double-blind, placebo-controlled phase 2 trial to evaluate the safety and efficacy of AYVAKYT in adult patients with ISM with moderate-to-severe symptoms not adequately controlled by best supportive care (BSC)1,2
Part 2 (pivotal part) evaluated the safety and efficacy of AYVAKYT 25 mg with BSC (141 patients) vs placebo with BSC (71 patients) over 24 weeks1,2
PIONEER study design1,2
Key inclusion criteria:1,2
- ≥18 years of age
- ISM confirmed by central pathology review
- Uncontrolled moderate to severe symptoms, defined as ISM-SAF TSS ≥28
Patient characteristics:1,2
- Patients were required to have failed to achieve adequate symptom control for 1 or more baseline symptoms with at least 2 symptomatic therapies
Primary endpoint:1,2
- Mean change in ISM-SAF TSS from from baseline to Week 24
Select key secondary endpoints:1,2
- Proportion of patients with ≥50% reduction in serum tryptase levels, KIT D816V VAF in peripheral blood and bone marrow mast cell burden at Week 24
- Proportion of patients achieving ≥50% and ≥30% reduction in TSS at Week 24
*OLE: ongoing open-label extension study is evaluating the long-term safety and efficacy of AYVAKYT 25 mg for up to 5 years.
**All eligible patients either continued AYVAKYT 25 mg daily or switched from placebo to AYVAKYT 25 mg daily.
Patient characteristics were balanced between both arms2
Patients were required to have failed to achieve adequate symptom control for 1 or more baseline symptoms with at least 2 symptomatic therapies1,2
Select baseline patient demographics (N=212)2
Patient characteristics
AYVAKYT + BSC (n=141)
Placebo + BSC (n=71)
Median age, years (range)
50 (18–77)
54 (26–79)
Sex
71% female, 29% male
76% female, 24% male
Mean ISM-SAF TSS (SD)
50.2 (19.1)
52.4 (19.8)
Median number of BSC treatments (range)†
3 (0–11)
4 (1–8)
Median serum tryptase level, ng/mL (range)
38.4 (3.6–256.0)
43.7 (5.7–501.6)
Positive KIT D816V mutation status, %
84%
89%
Mast cell aggregates present, %
75%
80%
†BSC medications allowed in the PIONEER study included but were not limited to: H1 antihistamines, H2 antihistamines, proton pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, cromolyn sodium and omalizumab.1,2
What is ISM SAF?
The ISM-SAF TSS is a validated measure of symptom severity in the PIONEER trial for ISM3
The Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) was developed with input from regulatory authorities, patients and therapeutic area experts2,3
Individual symptom scores are evaluated, and the 11 symptom severity scores are combined to calculate the total symptom score (TSS) (0–110):2,3‡
Scoring2,3
- Individual symptoms scored 0–10 daily
- 0=no symptom, 0=worst imaginable symptom
- A biweekly average ISM-SAF TSS was used to evaluate efficacy endpoints in PIONEER
‡ISM-SAF includes a 12th item on diarrhoea frequency which is not included in the TSS calculation.
BSC=best supportive care; ISM-SAF=Indolent Systemic Mastocytosis-Symptom Assessment Form; MAF=mutant allele fraction; QD=once daily; SD=standard deviation; TSS=total symptom score; OLE=open-label extension; VAF=variant allele fraction.
