PracticeUpdate: Dermatology - Winter 2018

CONFERENCE COVERAGE 28

BLZ-100 (Tozuleristide) Shown to Discriminate Between Subtle Molecular Subtypes of Basal Cell Carcinoma The first in-human study of BLZ-100 (tozuleristide), which selectively detects malignant tissue to enable more complete and precise surgical resection, has shown that the compound can discriminate between subtle molecular subtypes of basal cell carcinoma. M iko Yamada, PhD, of the University of Queensland in Brisbane, Aus- tralia, explained that skin cancer is " Successful surgery is a foundation of treatment and extent of resection is the single best predictor of survival in pediatric patients with brain tumors. I believe BLZ-100 as an aid to surgery has tremendous potential… "

often curable with complete excision. Wide margins are needed, however, particularly for cancers on the face. BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent (tumor paint) that selectively detects malignant tissue to ena- ble more complete and precise surgical resection. Surgery is first-line therapy for most solid tumor cancers. Tumor paint products intend to improve cancer surgery by providing real-time, high-resolution visualization of cancer cells throughout surgery. The ability to see cancer cells in real time and high resolution throughout surgery should enable better detection as well as more precise and complete surgical removal of cancer. Surrounding normal tissue is spared. The first tumor paint product candidate, BLZ- 100, is in phase I clinical trials for brain and breast cancers. Additional potential appli- cations of BLZ-100 include prostate, lung, colorectal, and other solid tumor cancers. BLZ-100 is administered by IV injection, circulates within the body, and “light ups” cancer cells. It consists of an Optide, which binds and internalizes into cancer cells, and a fluorescent dye, which emits light in the near-infrared range. Preclinical utility of BLZ-100 was demon- strated in a wide range of cancer types, including brain, breast, prostate, lung, colorectal, skin, and sarcomas. In this first in-human study, BLZ 100 was administered intravenously to 21 adult patients 2 days prior to excision of known/ suspected skin cancers. Doses were 1, 3, 6, 12, and 18 mg, with 3 to 6 patients per cohort. Fluorescence imag- ing was conducted before and up to 48 h after dosing. BLZ-100 was tolerated well. No serious adverse effects were observed. For intermediate dose levels (3–12 mg), 9 of 10 malignant lesions were considered positive for BLZ-100 fluorescence. This positivity led Dr. Yamada and col- leagues to explore differential gene expression profiles in basal cell carcinoma

part of the study has enrolled 15 pediatric patients at five prespecified dose levels to evaluate the safety and tolerability of BLZ- 100 and provide clinical proof of principle data for BLZ-100 to detect tumors in pedi- atric subjects. The dose expansion part of the study is ongoing. Lead investigator Sarah Leary, MD, of Seat- tle Children’s Hospital, said, in a press release, “We are continually inspired by our pediatric patients and their families, and aim to provide the best outcomes possi- ble for these children.” She continued, “Successful surgery is a foundation of treatment and extent of resec- tion is the single best predictor of survival in pediatric patients with brain tumors. I believe BLZ-100 as an aid to surgery has tremendous potential and look forward to further clinical testing in the pediatric pop- ulation.” www.practiceupdate.com/c/68650

tumors, the most homogeneous of the examined lesions. Gene expression profiles of BLZ 100-positive and -negative tumors were substantially similar. Significantly, differ- entially expressed genes were cytosolic, extracellular, and cell death genes. These modest differences were correlated to a binary staining profile that suggested that BLZ 100 can discriminate between subtle molecular subtypes of basal cell carcinoma, and possibly, melanoma. Dr. Yamada concluded that the results sup- port the safety of BLZ 100 at doses up to 18 mg. Ongoing studies are evaluating BLZ 100 safety and tissue tissue uptake in patients with other solid tumors. An open-label phase I dose escalation and expansion study is evaluating BLZ-100 in pediatric subjects with primary central nerv- ous system tumors. The dose escalation

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