Efficacy
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1. Trial design

2. Key exclusion and exclusion criteria

3. Baseline characteristics

4. Administration and study endpoints

5. Limitations of the SPRINT trial

6. Patient PN volume response over time
KOSELUGO® is indicated for the treatment of symptomatic, inoperable PN in paediatric patients with NF1 aged ≥ 3 years.1 Please refer to the KOSELUGO® SmPC for full prescribing information

The efficacy and safety of KOSELUGO® was evaluated in SPRINT Phase II Stratum 1, an open-label, multicentre, single-arm study, conducted on 50 paediatric patients with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) that caused significant morbidity.1,2

The SPRINT study is ongoing. Efficacy data are presented based on a data-cut-off of March 2021.1

Key inclusion criteria:3

  • Aged 2–18 years*

  • NF1 and at least one inoperable, symptomatic measurable PN

    • Inoperable PN was defined as PN that could not be completely removed surgically without risk for substantial morbidity due to encasement of, or close proximity to, vital structures, invasiveness or high vascularity of the PN

    • Measurable PN was defined as a lesion of at least 3 cm measured in one dimension and suitable for volumetric magnetic resonance imaging

  • ≥ 1 neurofibroma-related complication

  • Able to swallow intact capsules

Key exclusion criteria:3

  • Use of an investigational agent within the past 30 days

  • Individuals who were pregnant or breastfeeding because of a potential risk of foetal and teratogenic adverse events

  • Evidence of ongoing radiotherapy, chemotherapy, hormonal therapy directed at the tumour, immunotherapy or biologic therapy

  • Clinically significant uncontrolled unrelated systemic illness
*KOSELUGO® is indicated for the treatment of symptomatic, inoperable PN in paediatric patients with NF1 aged ≥ 3 years.1
The full list of the inclusion and exclusion criteria can be found here
The main limitation of the SPRINT trial is that it was not randomised or placebo controlled. Instead, the PN growth rate of patients was compared with age-matched external controls from the ongoing NCI NF1 natural history study.5,6
Primary endpoint: ORR
  • 68% (n = 34/50; 95% CI: 53.3, 80.5) of patients achieved a confirmed partial response (reduction in PN volume by ≥ 20% compared with baseline, confirmed at a subsequent tumour assessment within 3–6 months)1
  • No patients achieved a complete response1

Key secondary endpoints
At the time of data cut-off (March 2021) or last scan on treatment for patients who had discontinued KOSELUGO®, 50% (n = 25/50) remained in confirmed partial response1 
24% (n = 12/50) had stable disease, 20% (n = 10/50) had progressive disease, and 2% (n = 1/50) had unconfirmed partial response1

Adapted from: Gross AM et al. Neuro Oncol. 2023;25(10):1883–1894.5

Partial response was defined as > 20% tumor shrinkage from baseline (dashed line) and progressive disease was defined as > 20% increase from baseline or from best response if there was a prior partial response.5
78% of age-matched controls (n = 73/93) in the NCI NF1 natural history study had a PN volume increase of > 20% over the same time period as the SPRINT Phase II study (3.2 years).2 No patient in the natural history study had tumour shrinkage of > 20% during this time period.2
Adapted from: Supplement to: Gross AM et al. N Engl J Med. 2020;382(15):1430–1442.6
BSA, body surface area; CI, confidence interval; DoR, duration of response; NCI, National Cancer Institute; ORR, objective response rate; PN, plexiform neurofibromas.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Please report any adverse events via your national reporting system. Adverse events should also be reported to AstraZeneca by visiting https://contactazmedical.astrazeneca.com or by calling 0800 783 0033.
KOSELUGO® (selumetinib) EU Summary of Product Characteristics. Available from: https://www.ema.europa.eu/en/documents/product-information/koselugo-epar-product-information_en.pdf Last accessed: January 2024. Gross AM et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med. 2020;382(15):1430–1442. ClinicalTrials.gov. AZD6244. Available from: https://clinicaltrials.gov/ct2/show/NCT01362803. Last accessed: January 2024. Protocol for: Gross AM et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med. 2020;382(15):1430–1442. Gross AM et al. Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas. Neuro Oncol 2023;25(10):1883–1894. Supplement to: Gross AM et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med. 2020;382(15):1430–1442.