Phoenix Molecular Designs has launched a pivotal Phase 2 clinical trial investigating PMD-026 in combination with fulvestrant for patients with locally advanced or metastatic breast cancer. The trial, named Dauntless-1, marks a significant step forward in addressing treatment resistance in breast cancer therapy.
Novel Treatment Approach for CDK4/6 Resistant Breast Cancer
The trial specifically targets HR+/HER2-/RSK2-high breast cancer patients who have developed resistance to CDK4/6 inhibitor therapy. This patient population represents a significant clinical challenge, with approximately 70% of patients expressing high levels of nuclear RSK2. While fulvestrant, a selective estrogen receptor degrader (SERD), is commonly prescribed as second-line therapy, its effectiveness as a single agent typically lasts only 2-3 months.
PMD-026, developed as a first-in-class oral pan-RSK inhibitor, has demonstrated promising synergy with fulvestrant in preclinical models, particularly in those resistant to CDK4/6 inhibitors. This combination approach could potentially offer new hope for patients with limited treatment options.
Encouraging Early Clinical Evidence
The Phase 1/1b monotherapy studies of PMD-026 have yielded promising results. "PMD-026 demonstrated favorable tolerability, with no peripheral neuropathy, hair loss, or hyperglycemia," reported Dr. Sandi Dunn, Founder and CEO of Phoenix Molecular Designs. The drug showed particular efficacy in RSK2-high tumors, achieving a median progression-free survival of 4.8 months compared to 1.3 months in RSK2-low tumors among patients with no more than five prior therapies.
Strategic Trial Design and Clinical Impact
Dr. Brian Barnett, Chief Medical Officer, emphasized the significance of this milestone: "We are enthusiastic about PMD-026's clinical development and the potential to address an area of significant clinical unmet medical need in breast cancer patients with advanced HR+/HER2- breast cancer."
The trial's design reflects a targeted approach to patient selection, focusing on those most likely to benefit from the treatment based on their RSK2 expression levels. This precision medicine strategy, combined with the novel mechanism of action of PMD-026, represents a promising new direction in breast cancer treatment.
Safety Profile and Treatment Advantages
A notable aspect of PMD-026's development has been its favorable safety profile. The absence of common side effects associated with cancer treatments, such as peripheral neuropathy and hair loss, suggests potential quality-of-life benefits for patients. This tolerability profile, combined with the oral administration route, could offer significant advantages over existing therapies.
