Dialectic Therapeutics Initiates Phase 1b/2 Trial of DT2216 in Platinum-Resistant Ovarian Cancer
Key Insights
Dialectic Therapeutics has begun dosing the first patients in a Phase 1b/2 clinical trial testing DT2216 combined with paclitaxel for platinum-resistant ovarian cancer (search) at Dana-Farber Cancer Institute.
The novel BCL-XL (search) protein degrader DT2216 demonstrated complete tumor eradication in preclinical ovarian cancer models, including highly chemotherapy-resistant patient-derived xenografts.
The Phase 1a trial of DT2216 established a recommended Phase 2 dose with favorable safety profile and confirmed target engagement in all patients at the therapeutic dose level.
Dialectic Therapeutics has commenced patient dosing in a Phase 1b/2 clinical trial evaluating DT2216 combined with weekly paclitaxel for platinum-resistant ovarian cancer (search). The trial, led by Drs. Elizabeth Stover, Joyce Liu, and Ursula Matulonis from Dana-Farber Cancer Institute, has recruited its first two patients with additional candidates being evaluated for eligibility.
Dr. Stover serves as the principal investigator and IND-holder for the study, building on compelling preclinical data that demonstrated complete tumor eradication in ovarian cancer models. Dr. Matulonis, who previously led a study resulting in a recent FDA approval in platinum-resistant ovarian cancer (search), emphasized the urgent need for new therapeutic options in this patient population.
Novel BCL-XL Degradation Mechanism
DT2216 represents a novel therapeutic approach designed to potently and selectively degrade BCL-XL (search), a key protein that enables cancer cells to evade programmed cell death. This mechanism of action directly targets one of the fundamental pathways cancer cells use to resist treatment.
The drug's development builds on rigorous preclinical research conducted in collaboration with Dr. Kristopher Sarosiek at Harvard School of Public Health. In cancer cell line and patient-derived xenograft models of high-grade serous ovarian carcinoma (search), including the highly chemotherapy-resistant DF83 PDX model, the combination of paclitaxel and DT2216 induced rapid tumor regressions and achieved complete tumor eradication.
"The preclinical efficacy observed with DT2216 and paclitaxel is among the strongest results we have seen in preclinical models of high-grade serous ovarian cancer," stated Dr. Elizabeth Stover, Assistant Professor of Medicine at Harvard Medical School and medical oncologist in the Division of Gynecologic Oncology.
Phase 1a Results Support Clinical Advancement
The advancement to Phase 1b/2 testing follows successful completion of a Phase 1a dose-escalation study that enrolled and treated 20 patients across six cohorts. This initial trial established a recommended Phase 2 dose while demonstrating a favorable safety and tolerability profile.
Critically, biomarker analysis from patients receiving the recommended Phase 2 dose confirmed that DT2216 successfully degraded the intended BCL-XL (search) target protein in all patients within this dosing cohort, providing evidence of powerful and precise target engagement at therapeutic doses.
"As a lab that investigates how tumor cells commit to cell death, we're encouraged by how cleanly the biology matches the pharmacology," explained Dr. Sarosiek, Director of the Cell Death Laboratory at Harvard School of Public Health. "DT2216 selectively engages the target – BCL-XL (search) – and potently initiates tumor cell death in combination with paclitaxel."
Addressing Critical Unmet Medical Need
The clinical development of DT2216 addresses a significant gap in treatment options for platinum-resistant ovarian cancer (search) patients. Dr. Ursula Matulonis, Chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute and professor of Medicine at Harvard Medical School, noted that "new therapeutic options are very much needed for our patients with platinum-resistant ovarian cancer."
The preclinical data showed particularly promising durability, with tumors demonstrating no evidence of regrowth after DT2216 treatment was discontinued. This sustained response pattern suggests the potential for durable clinical benefit in patients.
John D. Harkey Jr., Executive Chairman of Dialectic Therapeutics, characterized the Phase 1b/2 trial initiation as "a critical milestone, driven by compelling data from our Phase 1a and preclinical studies."
The Texas-based clinical-stage biotechnology company has received multiple grants from the Cancer Prevention and Research Institute of Texas (CPRIT) to support the continued clinical development of DT2216, including a Seed and Company Product Research grant.