Cellectar Biosciences has submitted a Phase 1b clinical trial protocol to the U.S. Food and Drug Administration for CLR 125, an investigational Auger-emitting radiopharmaceutical designed to treat relapsed triple-negative breast cancer (TNBC). The submission represents a significant milestone for the late-stage clinical biopharmaceutical company's efforts to address one of the most challenging breast cancer subtypes.
Novel Auger-Emitting Approach
CLR 125 utilizes iodine-125 as an Auger-emitting isotope, integrated with Cellectar's proprietary Phospholipid Drug Conjugate (PDC) delivery platform. According to Jarrod Longcor, Cellectar's chief operating officer, the compound is designed to deliver iodine-125 directly to the nucleus and mitochondria, achieving potent activity while minimizing adverse effects due to its limited transmission range.
"Building on the promising preclinical results with CLR 125, we have submitted a Phase 1b dose-finding study protocol to the FDA for the treatment of triple-negative breast cancer, including metastatic disease," Longcor stated. The preclinical studies demonstrated good tolerability and robust tumor uptake in TNBC animal models.
Study Design and Endpoints
The proposed Phase 1b dose-finding study will enroll 45 patients with relapsed TNBC, divided into three arms of 15 patients each. The study will evaluate three distinct dosing regimens:
- 32.75 mCi administered over 4 cycles
- 62.5 mCi administered over 3 cycles
- 95 mCi administered over 2 cycles
Each regimen involves four doses per cycle, with imaging utilized to determine tumor uptake across the different dose levels. The primary endpoint focuses on determining the recommended Phase 2 dose and dosing regimen, while secondary endpoints include safety and tolerability assessments, as well as initial response evaluation using RECIST criteria and progression-free survival.
Platform Technology Advantage
James Caruso, chief executive officer of Cellectar, emphasized the therapeutic potential of combining the PDC-targeted delivery platform with precision-driven Auger-emitting isotopes. "The integration of our PDC-targeted delivery platform with a precision-driven, Auger-emitting isotope represents a powerful therapeutic combination with the potential to deliver significant clinical benefit across a range of solid tumors, including TNBC," Caruso explained.
The company's confidence in CLR 125 stems from its molecular similarity to iopofosine I 131, another PDC compound in Cellectar's pipeline that has demonstrated proof-of-concept and tolerability in Phase 2 clinical trials. Iopofosine I 131 has received FDA Breakthrough Therapy Designation and multiple regulatory designations across various cancer indications.
Addressing Critical Unmet Need
Triple-negative breast cancer presents significant treatment challenges due to the absence of estrogen receptors, progesterone receptors, and HER2 protein expression. This lack of common therapeutic targets limits treatment options primarily to chemotherapy. TNBC tends to grow and spread more rapidly than other breast cancer types and disproportionately affects younger women and those of African descent.
In the United States, approximately 12% of breast cancer diagnoses are TNBC. Studies indicate that approximately 25% of TNBC cases (40,540 patients) relapse after standard treatments including surgery, chemotherapy, and radiation. The high recurrence rate and poor prognosis create a critical need for innovative, targeted therapies to improve patient outcomes.
Broader Pipeline Context
CLR 125 represents part of Cellectar's broader PDC platform strategy targeting solid tumors including triple-negative breast, lung, and colorectal cancers. The company's pipeline also includes CLR 121225, an actinium-225 based program targeting solid tumors with significant unmet need such as pancreatic cancer, alongside multiple preclinical PDC chemotherapeutic programs and partnered assets.
The dosimetry imaging approach planned for the CLR 125 study is expected to provide early proof-of-concept by measuring drug delivery directly to tumors, potentially offering valuable insights for optimal dosing strategies in this challenging patient population.
