Chemotherapy Derivative Acelarin Shows Preliminary Activity in Platinum-Resistant Ovarian Cancer

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%.”

Reference:

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.