New therapy DT2216 tackles tough-to-treat ovarian cancer
Experimental drug targets BCL-XL protein that helps cancer cells evade death
A new experimental therapy, DT2216, has begun testing in a clinical trial for people with hard-to-treat ovarian cancer, a significant step forward announced by Dialectic Therapeutics.
The Phase 1b/2 study (NCT06964009) is targeting patients whose disease is relapsed or refractory, meaning it has either returned after initial treatment or failed to respond to previous therapies, including standard platinum-based chemotherapy. Researchers are particularly optimistic about DT2216 because it’s designed to attack a protein, BCL-XL, that cancer cells use to resist chemotherapy-induced death.
“The advance of DT2216 to this Phase 1b/2 trial represents a critical milestone, driven by compelling data from our Phase 1a and preclinical studies,” John D. Harkey Jr., executive chairman of Dialectic, said in a company press release.
The Phase 1b/2 study (NCT06964009) is expected to enroll 30 adults with relapsed or refractory ovarian cancer. To be eligible, patients must have received at least one previous round of a platinum-based chemotherapy drug, which is a mainstay of first-line treatment for ovarian cancer.
Trial design and objectives
All participants in the study will receive DT2216 in combination with paclitaxel, a standard chemotherapy drug. The study’s primary objective is to evaluate the safety of this experimental treatment regimen; its effects on disease progression and survival will also be closely monitored. The trial is being run at two sites in Boston, and it is currently recruiting patients. Additional information for prospective participants is available online.
“New therapeutic options are very much needed for our patients with platinum-resistant ovarian cancer. The preclinical data is extremely compelling in terms of the likelihood of translating to the clinical setting, and we are very excited to test weekly paclitaxel and DT2216 for ovarian cancer,” said Ursula Matulonis, MD, a professor at Harvard Medical School who is helping lead the trial.
DT2216, which is administered by infusion into the bloodstream, is designed to destroy BCL-XL.
The therapy “selectively engages the target — BCL-XL — and potently initiates tumor cell death in combination with paclitaxel,” which is “exactly the trajectory we hope to replicate in patients,” said Kristopher Sarosiek, PhD, a researcher at Harvard School of Public Health who helped conduct preclinical studies on DT2216. “We’ve long sought to develop innovative therapies that directly target the proteins responsible for making tumor cells resistant to treatment, and DT2216 offers us the opportunity to finally achieve this in patients.”
In preclinical experiments using mouse and human models, treatment with DT2216 in combination with paclitaxel led to “complete tumor eradication,” according to Dialectic.
Elizabeth Stover, MD, PhD, an assistant professor at Harvard Medical School and co-leader of the trial, stated that the therapy’s efficacy in lab experiments is “among the strongest results we have seen in preclinical models of high-grade serous ovarian cancer.”
A Phase 1a study (NCT04886622) had previously tested multiple doses of DT2216 in 20 adults with solid tumors. Results showed the therapy had an acceptable safety profile, with biomarker data indicating that it targeted the BCL-XL protein as designed. The study also established a recommended dose for the Phase 2 portion.
“It’s exciting to be able to bring a new potential treatment option to the clinic for our patients,” Stover said.
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