On March 10, 2020 NuCana plc (NASDAQ: NCNA) reported preliminary results from part one of the Phase II study of single-agent Acelarin in patients with platinum-resistant ovarian cancer (PRO-105) (Press release, Nucana BioPharmaceuticals, MAR 10, 2020, View Source [SID1234555368]). This part of the study compared a 500mg/m2 dose of Acelarin versus a 750mg/m2 dose of Acelarin in patients who were heavily pre-treated (at least 3 prior lines of chemotherapy). This study is now closed to recruitment and data analysis from part one of the study is ongoing.

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Forty-five patients with platinum-resistant ovarian cancer were evaluable for response and all responses had confirmatory scans. Based on an assessment by blinded independent central review, one patient achieved a complete response and two patients achieved partial responses. In addition, 16 patients achieved stable disease.

Patients who entered PRO-105 were heavily pre-treated, having received a median of five prior lines of treatment, and 72% had at least one comorbidity at study entry. Highlighting the fragility of this difficult-to-treat patient population, 45% of patients did not complete the first cycle of treatment with Acelarin despite not having any disease progression or any serious Grade 3 or 4 adverse events. However, for 23 patients in the study who received two or more cycles of Acelarin, the confirmed response rate was 13% and the disease control rate was 83%. These data are still being analyzed and the findings remain preliminary and subject to change.

NuCana’s CEO, Hugh S. Griffith, remarked: "We are pleased with this favorable disease control rate and Acelarin’s ability to achieve confirmed complete and partial responses in this very heavily pre-treated patient population. 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%."

The CLIO study reported on the efficacy of the current chemotherapy standards of care, namely paclitaxel, pegylated liposomal doxorubicin, topotecan and gemcitabine. Thirty-three patients received chemotherapy in the CLIO trial and were significantly less heavily pre-treated than those in the PRO-105 trial, with a median of 3 prior lines of treatment. However, given differences in trial design and statistical analyses, comparisons across studies should be interpreted with caution.

Part two of the PRO-105 study was designed to then investigate the optimal dose identified in part one in an expansion cohort. In December 2019, consistent with NuCana’s previous announcement that it is prioritizing resources on its key programs of Acelarin in biliary tract cancer and NUC-3373 in colorectal cancer, the company determined not to proceed with part two of the PRO-105 study.

Mr. Griffith concluded: "The advent of PARP inhibitors has changed the ovarian cancer treatment landscape markedly in recent years resulting in a more complex regulatory pathway for single-agent therapy. In addition, we have been very encouraged by the synergy we have observed with Acelarin in combination with platinum agents, both in patients with biliary tract cancer and ovarian cancer. As such, any further development of Acelarin in patients with ovarian cancer would likely involve combining it with a platinum agent."