Prostate Cancer
| stock.adobe.com
Treatment with the viral immunotherapy CAN-2409 (aglatimagene besadenovec) in combination with valacyclovir (Valtrex) and standard-of-care (SOC) external beam radiation therapy led to a statistically significant improvement in disease-free survival (DFS) vs SOC radiotherapy alone in patients with intermediate- to high-risk localized prostate cancer, meeting the primary end point of the phase 3 PrTK03 trial (NCT01436968).1
At a median follow-up of 50.3 months, patients in the intention-to-treat population in theCAN-2409 arm (n = 496) experienced a 30% reduction in the risk of disease recurrence or death compared with those in the SOC arm (n = 249; HR, 0.7; _P_ = .0155). At 54 months, there was a 14.5% relative improvement in DFS in the investigational arm vs the control arm. The improvement in DFS in the investigational arm was reported in patients who received short-term androgen deprivation therapy (ADT) and in those who did not.
Additionally, the 2-year pathological complete response (pCR) rate was 80.4% in the CAN-2409 arm compared with 63.6% in the control arm (_P_ = .0015). Patients in the investigational arm also 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).
“The improvement observed in DFS in this phase 3 clinical trial is clinically meaningful,” Glen Gejerman, MD, MBA, codirector of Urologic Oncology at Hackensack Meridian Health and a principal investigator of the study, stated in a news release. “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 SOC radiation. If approved, this approach has the potential to transform the treatment paradigm in prostate cancer, offering patients with localized disease an effective treatment option that may reduce the risk of disease recurrence.”
The investigational, off-the-shelf, replication-defective adenovirus CAN-2409 is designed to deliver the herpes simplex virus thymidine kinase gene to tumor cells. In combination with valacyclovir, the agent induces immunogenic cell death of tumor cells with exposure of tumor antigens in the context of an activated tumor microenvironment. Preclinical and clinical findings have shown that CAN-2409 can be synergistic with local radiation therapy.
PrTK03 was a double-blind, placebo-controlled, multicenter trial that enrolled adult patients with National Comprehensive Cancer Network intermediate- or high-risk prostate cancer with an ECOG performance status of 2 or less.2 Patients were required to undergo standard prostate-only external beam radiation therapy.
Eligible patients were randomly assigned 2:1 to receive CAN-2409 plus oral valacyclovir and radiation therapy or placebo plus oral valacyclovir and radiation therapy. Short-term ADT was optional for both arms. The first injection of CAN-2409 was administered at least 15 days and not more than 8 weeks before starting radiation, followed by the second dose 0 to 3 days before the initiation of radiotherapy. The third dose was given 15 to 22 days after the second injection. Patients in the control arm received the same regimen with placebo in place of CAN-2409.
The primary end point was DFS. Secondary end points included prostate cancer–specific survival, overall survival, PSA nadir, patient-reported quality of life, and safety.
Safety findings from PrTK03 showed that the safety profile of CAN-2409 was generally consistent with previous studies with no new safety signals.1 The most common any-grade adverse effects related to CAN-2409 included generally mild to moderate flu-like symptoms, fever, and chills.
Candel Therapeutics also reported findings from the phase 2 ULYSSES trial (NCT02768363) of CAN-2409 monotherapy in approximately 190 patients with low-to-intermediate risk localized prostate cancer undergoing active surveillance. Findings from the study demonstrated numerical improvement in time to radical treatment and the proportion of patients who achieved prostate cancer–free biopsies after 1 year of treatment; these differences did not reach statistical significance. The safety profile of CAN-2409 was mostly consistent with what was reported in PrTK03.
Candel Therapeutics plans to begin discussions with the FDA on the regulatory pathway for CAN-2409 in intermediate-to-high-risk localized prostate cancer. The full data from both studies will be presented at upcoming medical meetings.
“We are thrilled to report the phase 3 results for CAN-2409 in intermediate-to-high risk, localized prostate cancer,” Paul Peter Tak, MD, PhD, FMedSci, president and chief executive officer of Candel Therapeutics, added in the news release. “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. Importantly, this study was conducted under a Special Protocol Assessment agreed with the FDA, on key aspects of study design, meaning that safety and efficacy data generated from the study could be sufficient for the company to seek regulatory approval for CAN-2409 in this indication. We look forward to working with the FDA, as a next step, to seek approval to bring CAN-2409 to patients in the US and advance our broad viral immunotherapy pipeline across other large oncology indications of high unmet need.”
### **References**
1. Candel Therapeutics announces CAN-2409 achieved primary endpoint in phase 3 prostate cancer trial, showing significantly improved disease-free survival. News release. Candel Therapeutics. December 11, 2024. Accessed December 11, 2024. https://ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-announces-can-2409-achieved-primary-endpoint
2. Phase 3 study of ProstAtak® immunotherapy with standard radiation therapy for localized prostate cancer (PrTK03). ClinicalTrials.gov. Updated June 21, 2024. Accessed December 11, 2024. https://clinicaltrials.gov/st