Jason Chesney, M.D., Ph.D., acting director of the University of Louisville James Graham Brown Cancer Center, was study investigator on the Phase 2 ‘264 study that demonstrated Imlygic® (talimogene laherparepvec) in combination with the immune checkpoint inhibitor Yervoy® (ipilimumab) more than doubled objective response rate, defined as the proportion of patients with tumor size reduction, compared to Yervoy alone in patients with unresectable stage IIIB-IV melanoma. The results were presented at the 53rd Annual Meeting of the American Society of Clinical Oncology on June 3.
The analysis showed that 38.8 percent of patients treated with Imlygic plus Yervoy achieved an objective response versus 18 percent of patients treated with Yervoy alone. Patients in the combination arm also experienced nearly double the complete response rate compared to Yervoy alone (13.3 percent versus 7 percent). It was the first randomized study to evaluate the combination of Imlygic, an oncolytic viral therapy, with a checkpoint inhibitor.
“The results from this study demonstrate the potential of combining the complementary mechanisms of action of an oncolytic viral immunotherapy and a checkpoint inhibitor to enhance anti-tumor effect in patients with advanced melanoma,” one of the most difficult-to-treat types of cancer, said Chesney, who also serves as chief of the Division of Medical Oncology in UofL’s Department of Medicine.
Responses in the study were not limited to injected lesions. Among patients with visceral disease treated with IMLYGIC plus YERVOY, 35 percent had a reduction in size of visceral lesions by at least 50 percent. The rate was 14 percent in patients in the YERVOY arm.
The ‘264 study is a Phase 1b/2, multicenter, open-label trial evaluating the safety and efficacy of IMLYGIC in combination with YERVOY compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma. The primary endpoint of the Phase 2 portion of study is ORR. Secondary endpoints include duration of response, disease control rate, PFS, OS and safety. The study randomized 198 patients, 98 in the IMLYGIC plus YERVOY arm and 100 in the YERVOY arm.
Patients in the IMLYGIC plus YERVOY arm experienced a median progression-free survival (PFS) of 8.2 months (median follow-up at 68 weeks) versus 6.4 months in the YERVOY arm. While the effect was not statistically significant, the PFS analysis was not event-driven and is still ongoing, with only approximately 50 percent of PFS events reported at this time.
IMLYGIC is designed to rupture cancer cells causing the release of tumor-derived antigens, which along with granulocyte-macrophage colony-stimulating factor (GM-CSF), may help to initiate an anti-tumor immune response. However, the exact mechanism of action is unknown. This may be complementary to YERVOY’s mechanism of action, as the blockade of cytotoxic T-lymphocyte-associated antigen-4 has been shown to augment activation and proliferation of tumor infiltrating T-effector cells.
For more details, including safety information, visit the IMLYGIC website.