Acelarin demonstrated clinical activity in patients with platinum-resistant ovarian cancer who were heavily pretreated with at least 3 lines of chemotherapy, according to preliminary results from part 1 of phase II PRO-105 study, announced in a press release from the drug developer, NuCana plc.
Acelarin demonstrated clinical activity in patients with platinum-resistant ovarian cancer who were heavily pretreated with at least 3 lines of chemotherapy, according to preliminary results from part 1 of phase II PRO-105 study (NCT03146663), announced in a press release from the drug developer, NuCana plc.
The study included 51 participants, with 45 patients evaluable for response by confirmatory scans. Per Blinded Independent Central Review, 1 patient achieved a complete response, 2 patients achieved a partial response, and 16 patients had stable disease.
Among the study population, there was a median of 5 prior lines of therapy, and 72% of patients had at least 1 comorbidity at the start of the study. Patients were fragile, made evident by 45% of them not completing the first cycles of treatment with acelarin despite not experiencing disease progression and the absence of grade 3/4 adverse events (AEs). Among the 23 patients who did complete 2 or more cycles of therapy, the confirmed response rate was 13% and the disease control rate was 83%. These findings are subject to change as the data are still being analyzed.
In part 1 the open-label, 2-arm study, patients were treated with acelarin 500 mg/m2on days 1, 8, and 15 versus acelarin 750 mg/m2on days 1, 8, and 15. According to the protocol of the study, dose selection was based on clinical and laboratory assessments of the patients. Patients who were treated in part 1 could not be included in part 2.
Patients were eligible to enroll on the study if they were at least 18 years of age with an original diagnosis and/or a histological confirmation of high-grade serous, high-grade endometrioid, undifferentiated/unclassifiable epithelial ovarian, fallopian tube or primary peritoneal cancer, received at least 3 prior lines of chemotherapy for 6 months or less, and whose time from the last platinum-based chemotherapy was less than 6 months.
Patients were ineligible for PRO-105 if they progressed while receiving initial platinum-based chemotherapy; had prior treatment with single-agent gemcitabine; prior history of hypersensitivity to gemcitabine; prior chemotherapy or radiation treatment with a VEGF inhibitor, PARP inhibitor, or immunotherapy within 21 days of start of treatment during the study; prior hormone therapy within 14 day of starting treatment in the study; or residual AEs from chemotherapy or radiation. Individuals were also excluded if they had a serious illness, uncontrolled illness, active infection requiring antibiotics, serious medical history, active bacterial or viral infection, and a history of cancer within 5 years, with the exception of nonmelanoma skin cancer, cervical cancer or ductal carcinoma in situ that was adequately treated.
The goal of PRO-105 part 2 was to investigate the optimal dose identified in part 1 in an expansion cohort. But in December of 2019, NuCana chose to cancel the study to prioritize the study of acelarin in biliary tract cancer and another agent, NUC-3373, in colorectal cancer (CRC).
Acelarin is a first-in-class investigational agent derived from nucleoside analogs gemcitabine and 5-fluorouracil. It is currently under investigation in multiple clinical trials as treatment for patients with biliary tract cancer, platinum-resistant ovarian cancer, and metastatic pancreatic cancer.
“We are pleased with this favorable disease control rate and Acelarin’s ability to achieve confirmed complete and partial responses in this heavily pre-treated patient population, said Hugh S. Griffith,” CEO of Nucana. “We are further encouraged by these results in light of the recent CLIO study in less heavily pre-treated patients with platinum-resistant ovarian cancer, where no patients in the chemotherapy group achieved a complete response and only one patient achieved a confirmed partial response which resulted in a confirmed overall response rate of 3%.”
NuCana reports preliminary data from phase ii study of single-agent acelarin (nuc-1031) in patients with platinum-resistant ovarian cancer [news release]. Edinburgh, United Kingdom: NuCana plc; March 10, 2020. https://bit.ly/2xw1dJZ. Accessed March 11, 2020.