CLR 125 for advanced triple-negative breast cancer (Phase 1)

A Phase 1b, Open-Label Parallel Study Evaluating CLR 125 in Patients With Relapsed or Refractory Triple Negative Breast Cancer

This trial will test CLR 125 given by infusion in adults with advanced triple-negative breast cancer who have already had at least one prior therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cellectar Biosciences, Inc. (Industry-sponsored)
• Drugs / interventions: sacituzumab, trastuzumab, chemotherapy, immunotherapy, radiation
• Locations: 3 sites (Jacksonville, Florida and 2 other locations)
• Trial ID: NCT07311993 on ClinicalTrials.gov

What this trial studies

This phase 1 dose-escalation trial tests three dose levels of CLR 125 given by infusion to determine the recommended dose and characterize safety and tolerability in adults with advanced triple-negative breast cancer. Participants receive CLR 125 as four infusions each treatment cycle, with cycles repeated every eight weeks and clinic visits every three weeks for monitoring. A subset of patients will receive one dose of CLR 131 for dosimetry and undergo four scans and serial blood draws over two weeks to measure radiation distribution to organs and tumor. Up to 60 evaluable patients will be enrolled and antitumor activity will be tracked by RECIST v1.1 along with progression-free and overall survival measures.

Who should consider this trial

Good fit: Adults (≥18) with confirmed triple-negative breast cancer who progressed after at least one prior standard regimen, have ECOG performance status 0–2, and meet the required lab and organ-function criteria are the intended candidates.

Not a fit: Patients without triple-negative disease, those with inadequate blood counts or organ function, very limited life expectancy, or who cannot travel to a study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, CLR 125 could offer a new treatment option that shrinks tumors or slows disease progression for people with advanced triple-negative breast cancer who have exhausted standard therapies.

How similar studies have performed: Related targeted radiopharmaceuticals such as CLR 131 have shown early signals in other cancers, but CLR 125 in triple-negative breast cancer is a relatively new approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* Unequivocal TNBC histology \[ER and PR less than 10% each and HER-2 negative\].
* Patients that have progressed after at least one prior standard therapeutic regimen given alone or in combination (including, but not limited, to: chemotherapy, immunotherapy, sacituzumab govitecan-hziy, trastuzumab deruxtecan).

  * Patients who have received neo-adjuvant or adjuvant therapy must be at least one year from that treatment regimen.
* Patient is ≥ 18 years of age.
* ECOG performance status of 0 to 2.
* Life expectancy ≥ 6 months.
* Patient must meet the following laboratory criteria:

  * Platelets ≥ 75,000/uL \[75 x 10\^9/L\]
  * White blood cell (WBC) count ≥ 3000/uL
  * Absolute neutrophil count ≥ 1500/uL
  * Hemoglobin ≥ 9 g/dL
  * Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (as reported by the local lab)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN)
  * Bilirubin \< 1.5 × ULN
* At least one measurable lesion, as defined by RECIST v1.1, with longest diameter at baseline ≥ 10 mm (excluding lymph nodes, for which the short diameter must be ≥ 15 mm).
* Patients with known brain metastases must have completed any radiotherapy or systemic treatments for brain metastases prior to enrollment; by investigator assessment be considered stable with no new signs or symptoms for at least 1 month, and on a stable dose of steroids (unchanged for three weeks prior to registration or on a steroid tapering regimen).
* Patients must express willingness and ability to comply with scheduled study visits, treatment plans, laboratory tests, and other study procedures.
* Patient or their legally authorized representative must have the ability to understand and provide signed informed written consent before the initiation of any study-related procedures.
* Female patients of childbearing potential must have a negative pregnancy test within 24 hours of dosing.
* Women of childbearing potential must agree to use a highly effective method of contraception during the study and for 12 months following administration of the study drug. Highly effective methods of contraception include combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, vasectomized partner, or sexual abstinence. Women who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation, or are post-menopausal (no menses for 12 months without an alternative medical cause) are considered to be of non-childbearing potential.
* Men who are able to father a child must agree to use a condom during the study and for 12 months following administration of the study drug.

Exclusion Criteria:

* Antitumor systemic therapy or investigational therapy, within three-half-lives of the agent preceding study drug administration. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial.

  * Focal radiation (including palliative radiation) to non-target lesions should be completed at least 2 weeks prior to dosing.
  * For patients receiving CLR 125 after participation in the dosimetry phase, CLR 131 washout is not required prior to dosing with CLR 125.
* Prior targeted radiotherapy.
* Prior external beam radiation therapy resulting in greater than 20% of total bone marrow receiving greater than 20 Gy. For estimation purposes, the following bone marrow percentages can be used:

  * Vertebral bodies: Cervical 0.5%, thoracic 1%, lumbar 2% per vertebral body
  * Hemipelvis (ilium, acetabulum, ischium): 13% per side
  * Sacrum: 10%
  * Skull: 12%
  * Scapula: 5% per side
  * Ribs: 4% per side
  * Femur: 3% per side
* Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia, that in the opinion of investigator might be exacerbated by study treatment.
* Patients with prior or concurrent malignancy other than TNBC with the following exceptions, which must be fully treated with no evidence of disease for at least 2 years: non-melanoma skin cancers only requiring topical treatment or surgical excision; melanoma in situ; treated cervical carcinoma in situ; successfully treated prostate cancer.
* Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
* Known history of human immunodeficiency virus or uncontrolled, serious, active infection.
* Pregnancy or breast-feeding

Where this trial is running

Jacksonville, Florida and 2 other locations

• Mayo Clinic Florida — Jacksonville, Florida, United States (Not_yet_recruiting)
• United Theranostics — Glen Burnie, Maryland, United States (Recruiting)
• United Theranostics — Princeton, New Jersey, United States (Recruiting)

Study contacts

• Study coordinator: Kate Oliver

Conditions Breast Cancer; triple negative breast cancer