402P - Phase I study of selumetinib in Chinese pediatric and adult patients (pts) with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN): Interim results

Background

Selumetinib (ARRY-142886, AZD6244) is approved for pediatric pts aged ≥2 (US) or ≥3 (EU) years with NF1 and symptomatic, inoperable PN. We report interim results of a Phase 1, open-label study evaluating selumetinib for the first time in Chinese pediatric and adult pts with NF1 and inoperable PN.

Methods

Pts received oral selumetinib 25 mg/m² twice daily (BID) continuously in 28-day cycles until progressive disease or unacceptable toxicity. Primary endpoints were safety, tolerability, and pharmacokinetics (PK). Secondary endpoints included objective response rate (ORR; Response Evaluation in Neurofibromatosis and Schwannomatosis [REiNS]). This analysis was performed after the last dosed pt completed the first post-baseline response assessment at Cycle 4 Day 28.

Results

Overall, 16 pediatric (4–16 years, 56% male) and 16 adult (18–51 years, 56% male) pts were treated ; all remained on selumetinib at data cut-off (1/30/2022 ). The top two PN-related morbidities at baseline were pain (88%) and disfigurement (31%) in pediatric and pain (25%) and reduced range of motion (19%) in adult pts. All pts experienced ≥1 adverse event (AE). Decreased blood albumin (31%) and dermatitis acneiform (75%) were the most common AE in pediatric and adult pts, respectively; both are previously reported adverse reactions of selumetinib. No Grade 4 or 5 AEs were reported. Selumetinib was rapidly absorbed, metabolized, and eliminated. The median t_max,ss (h) was 1.5 in both groups. The geometric mean of C_max,ss (ng/mL) and AUC_(0-12),ss (h*ng/mL) was 1032 and 2961 in pediatric, and 1169 and 3932 in adult pts, respectively. Preliminary ORR data and PN volume versus baseline are given in the table.

Conclusions

At interim analysis, selumetinib at the 25 mg/m² BID dose approved in other countries showed acceptable safety, sufficient PK exposure, and a preliminary trend of efficacy in Chinese pediatric and adult pts with NF1 and inoperable PN Table: 402P

ICR, Independent central review; *≥20% tumor shrinkage (REiNS); ^†ORR: complete and confirmed partial response; ^‡n=15 had ≥1 post-baseline assessment

Clinical trial identification

NCT04590235.

Editorial acknowledgement

Editorial/ medical writing assistance in the preparation of this abstract was provided by Stavroula Bitsi of OPEN Health Communications (London, UK), with financial support from AstraZeneca.

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD).

Funding

AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD).

Disclosure

X. Yuan, X. Zhang, Q. Li, Z. Wang: Financial Interests, Institutional, Other, Medical writing support: AstraZeneca. C. Li, Y. Liu, X. Ge, J. Zhao: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Other, Medical writing support: AstraZeneca.