In patients with advanced, unresectable melanoma, the combination of talimogene laherparepvec (T-VEC) and ipilimumab yielded a higher objective response rate vs. ipilimumab alone, with a similar rate of severe or life-threatening ipilimumab-related toxicities, according to results of a 198-patient randomized phase II study.

Moreover, the incidence of grade 3/4 toxicities attributed to ipilimumab was similar between the two arms of the study, with no unexpected increases in treatment-related adverse events (AEs), reported Jason A. Chesney, MD, PhD, of the James Graham Brown Cancer Center, University of Louisville (Ky.), and his coinvestigators.

Taken together, the efficacy and safety findings suggest that the combination of T-VEC and ipilimumab “may have significant clinical utility in treatment of advanced melanoma,” Dr. Chesney and his colleagues wrote (J Clin Oncol. 2017 Oct. 5 doi: 10.1200/JCO.2017.73.7379).

The study included patients with unresectable stage IIIB/IV melanoma who had received no more than one previous treatment if BRAF wild type and no more than two treatments if BRAF mutant. Patients randomized to the combination arm received T-VEC starting in week 1 of the study and ipilimumab starting on week 6, while those in the single-agent arm received ipilimumab starting on week 1.

The primary endpoint of the phase II study was objective response rate by immune-related response criteria. Objective responses were seen in 38 of the 98 patients (39%) receiving T-VEC/ipilimumab, vs. 18 of the 100 patients (18%) who received ipilimumab alone (P = 0.002), the investigators said.

The incidence of grade 3 or greater AEs was 45% for the combination arm and 35% for the single-agent arm. There were three fatal AEs in the combination arm, but none was related to treatment, according to the investigators.

“Overall, combination treatment was not associated with unexpected AEs or increase in incidence or severity of AEs, suggesting that the combination therapy is tolerable for patients with advanced melanoma,” Dr. Chesney and his associates wrote.

Median progression-free survival (PFS) was 8.2 months for the combination arm and 6.4 months for ipilimumab alone (P = .35). Although the difference was not statistically significant, investigators remarked that ipilimumab was started later in the combination arm, per study design. Moreover, the 8.2-month median PFS exceeds the 2.8- to 2.9-month median PFS seen in previous ipilimumab studies, they said.

Combination immunotherapy is of great interest now in melanoma research. Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 antibody, while T-VEC is an attenuated herpes simplex 1 virus that expresses the immunostimulatory cytokine granulocyte–macrophage colony-stimulating factor. Some other combinations have shown promise, but with higher rates of toxicity, including the combination of ipilimumab plus nivolumab, which resulted in an increase in clinically significant AEs of grade 3 or greater, Dr. Chesney and his colleagues said.

“Combination regimens with lower toxicity may allow for their use in a broader range of patients,” they added.

The study was funded by Amgen, which manufactures talimogene laherparepvec. Dr. Chesney has a relationship with Amgen that involves consulting or advising; research funding; and travel, accommodation, and expenses. His associates reported financial relationships with Amgen and other companies; three of the investigators are Amgen employees.