Details

Autor(en) / Beteiligte

• Bauer, Todd M.
• Moore, Kathleen N.
• Rader, Janet S.
• Simpkins, Fiona
• Mita, Alain C.
• Beck, J. Thaddeus
• Hart, Lowell
• Chu, Quincy
• Oza, Amit
• Tinker, Anna V.
• Imedio, Esteban Rodrigo
• Kumar, Sanjeev
• Mugundu, Ganesh
• Jenkins, Suzanne
• Chmielecki, Juliann
• Jones, Suzanne
• Spigel, David
• Fu, Siqing

Titel

A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors

Ist Teil von

• Targeted oncology, 2023-07, Vol.18 (4), p.517-530

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2023

Quelle

SpringerLink

Beschreibungen/Notizen

• Background Adavosertib (AZD1775) is a first-in-class, selective, small-molecule inhibitor of Wee1. Objective The safety, tolerability, pharmacokinetics, and efficacy of adavosertib monotherapy were evaluated in patients with various solid-tumor types and molecular profiles. Patients and Methods Eligible patients had the following: confirmed diagnosis of ovarian cancer (OC), triple-negative breast cancer (TNBC), or small-cell lung cancer (SCLC); previous treatment for metastatic/recurrent disease; and measurable disease. Patients were grouped into six matched cohorts based on tumor type and presence/absence of biomarkers and received oral adavosertib 175 mg twice a day on days 1–3 and 8–10 of a 21-day treatment cycle. Results Eighty patients received treatment in the expansion phase; median total treatment duration was 2.4 months. The most common treatment-related adverse events (AEs) were diarrhea (56.3%), nausea (42.5%), fatigue (36.3%), vomiting (18.8%), and decreased appetite (12.5%). Treatment-related grade ≥ 3 AEs and serious AEs were reported in 32.5% and 10.0% of patients, respectively. AEs led to dose interruptions in 22.5%, reductions in 11.3%, and discontinuations in 16.3% of patients. One patient died following serious AEs of deep vein thrombosis (treatment related) and respiratory failure (not treatment related). Objective response rate, disease control rate, and progression-free survival were as follows: 6.3%, 68.8%, 4.5 months (OC BRCA wild type); 3.3%, 76.7%, 3.9 months (OC BRCA mutation); 0%, 69.2%, 3.1 months (TNBC biomarker [ CCNE1 / MYC / MYCL1 / MYCN ] non-amplified [NA]); 0%, 50%, 2 months (TNBC biomarker amplified); 8.3%, 33.3%, 1.3 months (SCLC biomarker NA); and 0%, 33.3%, 1.2 months (SCLC biomarker amplified). Conclusion Adavosertib monotherapy was tolerated and demonstrated some antitumor activity in patients with advanced solid tumors. Trial Registration ClinicalTrials.gov identifier NCT02482311; registered June 2015.