The novel agent ABSK061 approached a response rate of 40% in patients with advanced solid tumors harboring FGFR2/3 alterations.
Findings from a first-in-human phase 1 trial (NCT05244551) presented at the 2024 ESMO Targeted Anticancer Therapies Congress showed that the selective FGFR2/3 inhibitor ABSK061 is safe and induced anti-tumor activity in patients with advanced solid tumors—including urothelial carcinoma—harboring FGFR2/3 alterations.1
Results showed that patients evaluable for efficacy (n = 8) experienced an overall response rate (ORR) of 37.5%, which was comprised entirely of partial responses (PRs). The disease control rate (DCR) was 75%. Among 3 of the patients to achieve a PR, 1 patient had non–small cell lung cancer (NSCLC) and received 4 prior lines of therapy; another patient presented with urothelial carcinoma and had received 2 prior lines of therapy; and the third patient had gastric cancer with 2 prior lines of therapy.
In the safety population (n = 29), no dose-limiting toxicities (DLTs) were reported during dose escalation. Treatment-related adverse effects (TRAEs) were generally low grade and reversible, and no patients discontinued treatment due to TRAEs. The most common any-grade TRAEs were increased aspartate aminotransferase (AST) and increased alanine aminotransferase (ALT), which each occurred in 31% of patients.
Regarding AST/ALT elevation, lead study author Ji Zhu, MD, noted that nearly half of patients in the safety population had liver metastases.
“Dose-escalation data validate ABSK061 as the first highly selective FGFR2/3 inhibitor that targets driver alterations,” Zhu said in a presentation of the data. Zhu is a member of the Department of Radiotherapy Oncology at Zhejiang Cancer Hospital in Hangzhou, China.
Preclinical models demonstrated that ABSK061 exhibited higher selectivity for FGFR2/3 compared with FGFR1, informing the hypothesis that this selectivity could lead to decreased toxicities and improved efficacy in clinical trials.
The open-label, phase 1 study enrolled patients with solid tumors who progressed on, were intolerant to, or declined standard-of-care therapy.1,2 Patients were required to have an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; and adequate organ and bone marrow function.
During dose escalation, patients received ABSK061 at 5 mg twice per day (n = 1), 10 mg twice per day (n = 1), 20 mg twice per day (n = 1), 35 mg twice per day (n = 3), 50 mg twice per day (n = 3), 75 mg twice per day (n = 7), 100 mg twice per day (n = 3), or 150 mg once per day (n = 4). Two cohorts also examined recommended doses for expansion (RDEs) at 150 mg once per day (n = 3) and 75 mg twice per day (n = 3). Enrollment is ongoing in the RDE cohorts, where patients are required to have activating FGFR2/3 alterations.1
Incidence of DLTs and AEs served as the primary end points of the study. Secondary end points included ORR, duration of response, DCR, progression-free survival, and pharmacokinetics.2
In the safety population, the median age was 54.0 years (range, 46.0-63.0), and 44.8% of patients were female. The majority of patients were Asian (96.6%) and had an ECOG performance status of 1 (93.1%). Prior lines of systemic therapy included 0 (3.4%), 1 (24.1%), 2 (37.9%), and 3 or more (34.5%). Notably, 93.1% of patients received prior chemotherapy, and 58.6% were previously treated with immunotherapy.1
Tumor types included bladder cancer (3.4%), cervical cancer (13.8%), cholangiocarcinoma (10.3%), colorectal cancer (10.3%), esophageal cancer (3.4%), gastric cancer (17.2%), gastroesophageal cancer (3.4%), NSCLC (10.3%), pancreatic cancer (6.9%), sarcoma (10.3%), small cell lung cancer (3.4%), and other (6.9%).
Additional safety data showed that other common any-grade TRAEs reported in at least 15% of the safety population included retinal pigment epithelial dystrophy/central serous retinopathy (RPED/CSR; 20.7%), increased alkaline phosphatase (17.2%), anemia (17.2%), hyperphosphatemia (17.2%), and diarrhea (17.2%). Grade 3 or higher increased AST and increased ALT each occurred in 3.4% of patients. Notably, all instances of RPED/CSR and hyperphosphatemia were grade 1 and reversible.
The rates of stomatitis, dry mouth, nail toxicity, alopecia, and palmar-plantar erythrodysesthesia were 10.3%, 6.9%, 3.4%, 3.4%, and 3.4%, respectively. No treatment-related dry eye was reported.
Vobramitamab duocarmazine continues to show promise in mCRPC
May 10th 2024Updated data from the phase 2 TAMARCK study continued to show safety and preliminary efficacy with the B7-H3–targeting antibody-drug conjugate vobramitamab duocarmazine in patients with metastatic castration-resistant prostate cancer.
Expert discusses novel approach to ctDNA detection in MIBC
May 2nd 2024"[This] shows a different approach for detecting circulating tumor DNA in bladder cancer patients, and it opens up the possibility for other biorepositories that have serum samples to also enter the ctDNA research environment," says Richard T. Bryan, MBChB, PhD, MRCS, FacadTM.