Pegloprastide (also known as AVB-620) has completed a Phase 2/3 pivotal clinical trial for fluorescent detection of cancer during breast cancer surgery (NCT03113825), as well as a Phase 1b clinical trial in women undergoing breast cancer surgery (NCT02391194).

An Open-Label, Single-Arm, Phase 2 Study of AVB-620 in Women with Primary, Nonrecurrent Breast Cancer Undergoing Surgery (NCT03113825

The pivotal study of pegloprastide was a multi-center, open-label, single-arm study designed to evaluate patients during two separate trial periods (Period 1 and Period 2). Both study periods enrolled women with the most common breast cancer types – ductal carcinoma in situ (DCIS) (Stage 0) and/or Stage I-III invasive carcinoma – with all grades (Grades 1-3) and all receptor statuses. Over 120 women undergoing breast cancer surgery were enrolled over both trial periods. Imaging of pegloprastide was performed on all types of tissue, including excised specimen, cavity shaves, and residual tissue left in the surgical cavity.

Period 1, which was completed in December 2017, enrolled 32 patients and demonstrated proof-of-concept that pegloprastide could sensitively visualize the primary tumor in the lumpectomy specimen. In additional, optimal dosing and imaging conditions, including fluorescent thresholds, to achieve differentiation between malignant and nonmalignant tissue in margin-relevant tissue was determined. Initial trial results were presented at San Antonio Breast Cancer Symposium 2018 (SABCS).

Period 2, which was completed in March 2020, enrolled 92 additional patients to prospectively assess the ability of pegloprastide to identify malignant tissue at or close to the surface of excised tissue and of tissue that would have been left behind and require a reoperation to remove.

Top-line data from this pivotal study period revealed that pegloprastide has the potential to significantly improve cancer detection in real-time during breast cancer surgery. Top-line data analysis found that:

  • Use of pegloprastide during surgery met its primary endpoint of detecting cancer in margin specimens in real time (p < 0.001)
  • Use of pegloprastide during surgery correctly identified cancer in up to 75% of patients who would have otherwise been candidates for a re-excision surgery
  • 81% overall accuracy of pegloprastide in detecting true positive and true negative patients
  • The planned re-excision rate for patients who underwent an initial breast conserving surgery with pegloprastide was 6%, much lower than the current estimated re-excision rate of 20-40% among women undergoing an initial lumpectomy

Phase 1 Trial of AVB-620 in women with Primary, Non-Recurrent Breast Cancer Undergoing Surgery (NCT02391194

Avelas’ first-in-human Phase 1 study examined the safety and tolerability of pegloprastide administered as an IV infusion to women with primary, non-recurrent breast cancer undergoing surgery. A total of 27 women received pegloprastide during this two-part, multi-institutional trial. No adverse events or laboratory values attributable to infusion of pegloprastide were found. By the time of surgery, there were measurable differences between tumor-positive and tumor-negative tissue allowing for separation between them based on fluorescence imaging analysis.

Data from this clinical trial has been published in the Annals of Surgical Oncology in a paper titled “Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase I Study”.

For more information Avelas’ clinical trials, please visit ClinicalTrials.gov.