Padeliporfin VTP Converts Inoperable Pancreatic Tumors to Resectable in Early Phase 1 Data
核心洞察
ImPact Biotech (搜索)'s padeliporfin vascular targeted photodynamic therapy is being tested in a first-in-human U.S. Phase 1 trial in unresectable locally advanced pancreatic ductal adenocarcinoma (搜索).
UCI Health (搜索) reported that six patients received the treatment and four subsequently underwent surgery, with three showing no cancer cells at surgical margins.
Earlier ASCO data showed five of seven evaluable patients (71%) across two dose levels proceeded to surgery, including four with negative margins.
An Israeli-developed cancer technology is being tested in a first-in-human U.S. Phase 1 clinical trial against pancreatic tumors that cannot be surgically removed because they encase major abdominal arteries, with preliminary results showing that some treated patients became eligible for surgery.
Tel Aviv-based ImPact Biotech (搜索)'s Padeliporfin Vascular Targeted Photodynamic therapy, or VTP, is being evaluated in patients with locally advanced pancreatic ductal adenocarcinoma (搜索) considered unresectable due to tumor encasement around major arteries. UCI Health (搜索), the clinical enterprise of the University of California, Irvine, is one of only two U.S. cancer centers participating in the study.
Early Surgical Conversion Signal
UCI Health (搜索) reported this month that six patients had received the treatment and four subsequently underwent surgery to remove remaining tumor tissue. Three of those four patients had no cancer cells detected at their surgical margins. The first three participants were described in preliminary results published in the Journal of Vascular and Interventional Radiology; another three patients have since received the targeted low-light therapy.
Earlier data released by ImPact Biotech (搜索) at the American Society of Clinical Oncology meeting in May included seven evaluable patients across two dose levels. Five of those seven, or 71 percent, underwent surgery after treatment, including four patients whose resections produced negative surgical margins. The differing patient totals reflect data reported at different stages of the developing trial and should not be interpreted as mature efficacy results.
The findings remain preliminary and come from an early-stage trial primarily designed to evaluate safety and determine an appropriate treatment dose. They do not establish that the therapy is effective and will require confirmation in larger studies. No randomized comparison with standard treatment has yet been completed.
Delivering Light Inside the Artery
The ImPact Biotech (搜索) approach targets the tumor from inside the affected blood vessel. Patients are first given padeliporfin, a light-sensitive drug, administered by injection. Physicians then position a catheter containing a laser illumination device—described as a balloon inserted into the tumor-encased blood vessel—within the artery surrounding the tumor. The drug is activated using precisely delivered, non-thermal laser light.
That illumination causes a photochemical reaction within the tumor's blood vessels, breaking down the tumor's vascular network and ultimately destroying tumor tissue surrounding the artery. UCI Health (搜索) delivers the treatment in two five-minute illumination periods, after which physicians allow approximately two weeks for the treatment effect to develop before assessing whether the remaining tumor can be removed surgically. As part of the Phase 1 trial, the clinical research team is testing three incremental doses of laser illumination to determine the most effective one.
Patients must spend three days in a dark room after treatment because exposure to light could cause damage to other areas of the body, including the skin—a constraint that has limited the therapy's use to smaller treatment areas.
"We use the light-sensitive drug padeliporfin to destroy pancreatic tumors encasing major arteries in the abdomen – once the vessels are clear of tumors, patients can undergo what can be a lifesaving surgery," said UCI Health (搜索) radiologist Dr. Nadine Abi-Jaoudeh, lead investigator of the trial and a professor of radiology at the UC Irvine School of Medicine. Co-investigators include UCI Health medical oncologist Dr. Jennifer B. Valerin and surgeons Dr. David K. Imagawa and Dr. Zeljka Jutric.
Why Unresectable Disease Matters
Pancreatic cancer has one of the lowest survival rates of all cancers. According to UCI Health (搜索), about half of pancreatic cancer patients have localized disease when evaluated, but approximately two-thirds of those patients cannot undergo surgery—usually because their tumors wrap around major arteries that deliver blood to the abdomen, making conventional surgery too dangerous.
Abi-Jaoudeh said patients with localized cancers who cannot undergo surgery can have survival outcomes comparable to those whose cancer has metastasized. "This is a significant finding because patients with localized cancers who cannot undergo surgery have similarly low survival rates as patients with metastasized pancreatic cancer," she said of the early results.
The goal of Padeliporfin VTP is therefore not simply to shrink a tumor, but to selectively eliminate enough cancer around key vessels to change the patient's surgical status. The trial is prospective, multicentre, non-randomized and open-label, with preliminary efficacy assessed by determining whether patients initially judged inoperable can subsequently undergo surgery. It is expected to enroll up to 30 participants and is currently listed as accepting patients at the University of California, Irvine and City of Hope (搜索) in California.
Parallel Phase 3 Program in Urothelial Cancer
The pancreatic cancer trial is not the only major clinical program underway for ImPact Biotech (搜索). The company announced Sept. 9 that all 91 required patients had completed treatment in its Phase 3 ENLIGHTED trial evaluating Padeliporfin VTP for low-grade upper tract urothelial carcinoma (搜索), a cancer affecting the lining of the kidney or ureter. The international study spans 29 clinical sites.
In that application, physicians deliver padeliporfin intravenously and activate it using a laser fiber positioned near the tumor during ureteroscopy. ImPact said it expects to present additional interim data at the European Society for Medical Oncology Congress in October and is working toward a U.S. regulatory submission in 2027. Written feedback following an April meeting with the U.S. Food and Drug Administration (搜索) supported a potential path toward submitting a New Drug Application next year, according to the company—though that does not amount to FDA approval or a guarantee that the therapy will ultimately be authorized.
The significance of the two programs is that ImPact Biotech (搜索) is applying the same underlying platform against very different solid tumors. In upper tract urothelial cancer, the company is already conducting a pivotal Phase 3 study; in pancreatic cancer, development remains considerably earlier, with researchers still establishing safety, dosing and preliminary evidence of whether the treatment can make otherwise unresectable disease operable.
A handful of successful surgeries cannot demonstrate that the approach will improve survival or work in a broader population. But early conversion of patients from inoperable to operable status provides researchers with a clinical signal worth investigating. If larger trials eventually confirm that Padeliporfin VTP can safely clear tumor tissue from around major arteries and allow more pancreatic cancer patients to undergo potentially curative surgery, the technology could address one of the most difficult problems in oncology. If the investigative team confirms the approach is effective, the hope is to move on to Phases 2 and 3 which, once approved by the FDA, would test VTP therapy in significantly more patients.