Candel Therapeutics' CAN-2409, a viral immunotherapy, has demonstrated promising results in a Phase 3 clinical trial for localized prostate cancer. The PrTK03 trial met its primary endpoint, showing a statistically significant improvement in disease-free survival (DFS) among patients with intermediate- to high-risk localized prostate cancer when CAN-2409 was combined with valacyclovir and standard of care radiation therapy, compared to radiation therapy alone. This advancement offers a potential new treatment option for patients facing this common malignancy.
Significant Improvement in Disease-Free Survival
The Phase 3 trial involved 496 patients receiving CAN-2409 plus radiation therapy and 249 patients receiving radiation therapy alone. At a median follow-up of 50.3 months, the CAN-2409 arm experienced a 30% reduction in the risk of disease recurrence or death (HR, 0.7; P = .0155). At 54 months, a 14.5% relative improvement in DFS was observed in the investigational arm compared to the control arm. This improvement was consistent in patients who received short-term androgen deprivation therapy (ADT) and those who did not.
Dr. Glen Gejerman, Co-Director of Urologic Oncology at Hackensack Meridian Health and a principal investigator of the study, stated, "The improvement observed in disease-free survival in this phase 3 clinical trial is clinically meaningful. We have not seen significant advances in this indication in decades. CAN-2409 has demonstrated the potential to significantly improve long-term outcomes without adding substantial toxicity to standard of care radiation."
Pathological Complete Response and Prostate Cancer-Specific Survival
In addition to the primary endpoint, the trial also revealed a significant improvement in pathological complete response (pCR) rates. The 2-year pCR rate was 80.4% in the CAN-2409 arm compared to 63.6% in the control arm (P = .0015). Furthermore, patients in the investigational arm experienced a significant improvement in prostate cancer–free survival compared with the control arm (HR, 0.6; P = .0046). The proportion of patients who achieved a prostate-specific antigen (PSA) nadir (<0.2 ng/mL) was 67.1% vs. 58.6%, respectively (P < .0164).
CAN-2409 Mechanism and Safety Profile
CAN-2409 is an off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase gene to tumor cells. When combined with valacyclovir, it induces immunogenic cell death of tumor cells, exposing tumor antigens in an activated tumor microenvironment. The safety profile of CAN-2409 in the PrTK03 trial was consistent with previous studies, with common adverse effects including mild to moderate flu-like symptoms, fever, and chills.
Future Directions
Candel Therapeutics also reported findings from the Phase 2 ULYSSES trial of CAN-2409 monotherapy in patients with low-to-intermediate risk localized prostate cancer undergoing active surveillance. While the study demonstrated numerical improvements in time to radical treatment and the proportion of patients achieving prostate cancer-free biopsies after one year, these differences were not statistically significant.
Dr. Paul Peter Tak, President and Chief Executive Officer of Candel Therapeutics, expressed enthusiasm about the results, stating, "This study validates previous observations of CAN-2409 activity seen in difficult-to-treat solid tumors, often resistant to immunotherapy, and confirms our previous observation of synergies with radiation therapy in models of prostate cancer." Candel Therapeutics plans to engage with the FDA to discuss the regulatory pathway for CAN-2409 in intermediate-to-high-risk localized prostate cancer.
