Adding CAN-2409 to radiation improves DFS in localized prostate cancer

The phase 3 PrTK03 trial (NCT01436968) has met its primary end point by demonstrating that the addition of aglatimagene besadenovec (CAN-2409) viral immunotherapy to radiation therapy significantly improved disease-free survival (DFS) vs radiation alone in patients with localized prostate cancer, Candel Therapeutics reported in a news release.¹

According to the company, “CAN-2409 is an investigational, off-the-shelf, replication-defective adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to tumor cells.” The immunotherapy is designed to work in combination with valacyclovir (prodrug) to induce immunogenic cell death of tumor cells.

Glen Gejerman, MD

“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,” said co-principal investigator Glen Gejerman, MD, co-director of urologic oncology at Hackensack Meridian Health's John Theurer Cancer Center, in the news release.¹ “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.”

Overall, data from the trial showed that patients who received the combination of CAN-2409 and radiation therapy demonstrated a 14.5% relative improvement in DFS at 54 months compared with those who received radiation alone (P = .0155; HR, 0.7). This finding was consistent in both patients receiving short-term androgen deprivation therapy (ADT) and in those not receiving ADT.

CAN-2409 also demonstrated a highly significant effect on prostate cancer-free survival (P = .0046; HR, 0.6) in a secondary analysis.

Further, 67.1% of patients in the combination arm vs 58.6% of patients in the radiation alone arm achieved a prostate-specific antigen (PSA) nadir, defined as less than 0.2 ng/mL. Pathologic complete responses per 2-year treatment biopsies were achieved in 80.4% of patients who received CAN-2409 plus radiation vs 63.6% of patients who received radiation alone (P = .0015).

No new safety signals were identified in this study. Treatment-related adverse events (TRAEs) were generally mild to moderate and self-limited. The most common TRAEs were flu-like symptoms and fever and chills.

In total, the study enrolled 745 patients with intermediate- to high-risk localized prostate cancer across 73 clinical trial sites in the US and Puerto Rico. To be eligible for enrollment, patients needed to have intermediate-risk disease per National Comprehensive Cancer Center criteria, a plan to undergo standard EBRT for the prostate only, and an ECOG performance score of 0 to 2.²

Those included in the study were randomly assigned 2:1 to receive the combination of CAN-2409 plus valacyclovir plus external beam radiation therapy (EBRT) or to placebo plus valacyclovir plus EBRT. All patients had the option to receive short-term (less than 6 months) androgen deprivation therapy (ADT). The median follow-up time for patients was 50.3 months.

The primary end point was DFS. Secondary end points included prostate cancer-specific survival, PSA nadir, quality of life measures, and safety.

In addition to these phase 3 results, Candel Therapeutics also reported data from their phase 2 ULYSSES trial (NCT02768363) of CAN-2409 monotherapy in 190 patients with low- to intermediate-risk localized prostate cancer undergoing active surveillance. Overall, CAN-2409 demonstrated numerical improvements in the time to radical treatment and the percentage of patients will negative biopsies at 1-year following treatment. However, these findings did not reach statistical significance.

Results from both the phase 2 and phase 3 trials of CAN-2409 will be presented during upcoming medical meetings, the company reported. Candel also noted that they will be initiating discussions with the FDA to discuss a regulatory pathway for CAN-2409 in intermediate- to high-risk localized prostate cancer.

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 13, 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. Last updated June 21, 2024. Accessed December 13, 2024. https://clinicaltrials.gov/study/NCT01436968