Acelarin Trial Shows Potential in Chemo-resistant Ovarian Cancer, But Study Ending

Treatment with Acelarin led to one complete response and two partial responses in heavily pre-treated women with platinum-resistant ovarian cancer, early results from a Phase 2 trial show.

Full analysis of the study’s first part is ongoing. However, the treatment’s developer, NuCana, has decided not to continue with a planned second part to focus on trials in other cancers.

Acelarin (NUC-1031) is designed to help patients overcome resistance to common chemotherapies, such as platinum-based chemotherapies. It is based on the structure of two chemotherapy agents, gemcitabine (sold as Gemzar by Eli Lilly, among other brands) and 5-fluorouracil. The idea is that a combination of the agents will be more effective than either treatment alone, and able to overcome treatment resistance.

The PRO-105 trial (NCT03146663) tested Acelarin alone in ovarian cancer patients with a median of five prior lines of chemotherapy treatment. The study, conducted in the U.S. and U.K., was divided in two parts: in part one, women receive one of two Acelarin doses — 500 or 750 mg/m² — on days one, eight, and 15.

In total, 45 women with platinum-resistant ovarian cancer were enrolled for part 1. The majority (72%) had at least one additional disease (comorbidity) at the trial’s start.

This may have contributed to almost half of the participants (45%) not being able to complete the first round of Acelarin treatment, despite a lack of disease progression or serious adverse effects. In total, 23 women completed two or more cycles of Acelarin in part 1.

Preliminary results show that 19 women (83%) experienced disease control, with three (13%) responding to treatment.

Specifically, a review by an independent panel reported that one woman achieved a complete response, meaning complete cancer disappearance, and two achieved partial responses, or tumors that diminished in size. NuCana noted these findings are preliminary.

“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,” Hugh S. Griffith, the CEO of NuCana, said in a press release.

In part 2, an additional group of women were to be given Acelarin at optimal dose, as determined in part 1, until disease progression. Instead, the company decided to focus on advancing Acelarin for biliary tract cancer and NUC-3373 for colorectal cancer.

“[W]e 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,” Griffith said. “As such, any further development of Acelarin in patients with ovarian cancer would likely involve combining it with a platinum agent.”