From the Journals

T-VEC plus pembrolizumab yields promising response rate in phase 2 sarcoma study


 

FROM JAMA ONCOLOGY

The combination of oncolytic immunotherapy and an immune checkpoint inhibitor had promising activity in a phase 2 study including patients with previously treated advanced sarcoma, investigators report.

Responses were seen in about one-third of the patients (30%) at 24 weeks after starting treatment with talimogene laherparepvec (T-VEC) and pembrolizumab, according to the investigators, led by Ciara M. Kelly, MBBChBAO, MD, of the department of sarcoma oncology at Memorial Sloan Kettering Cancer Center, New York.

“To our knowledge, this is one of the highest ORRs [objective response rates] reported in an unselected sarcoma-specific study population evaluating the efficacy of combination immunotherapy,” Dr. Kelly and coauthors wrote in JAMA Oncology.

Two of the patients who responded to the combination had previously failed regimens that included an immune checkpoint inhibitor, suggesting T-VEC might be augmenting the efficacy of pembrolizumab, according to the authors.

Among responders, the mean number of prior treatments was one, while by contrast, most of the study cohort (60%) had three or more prior treatments. “This finding supports the rationale to enroll patients with sarcoma in immunotherapy trials earlier in their treatment course,” Dr. Kelly and colleagues wrote.

In studies of immunotherapy in Merkel cell carcinoma and other cancer types, higher response rates have been seen in patients who were naive to chemotherapy, as opposed to those who were refractory to it.

The present single-institution, phase 2 study by Dr. Kelly and colleagues included 20 adult patients with histologically confirmed locally advanced or metastatic sarcoma. The patients received a fixed dose of pembrolizumab administered intravenously, and had T-VEC injected into palpable lesions, on day 1 of 21-day cycles.

While the ORR was 30% at 24 weeks (7 of 35 patients), an additional patient had a response at 32 weeks, bringing the ORR to 35%, according to the report.

“Maximal response to therapy may take a prolonged period to achieve,” the investigators wrote, noting that the median time to response was 14.4 weeks.

Median duration of response was 56.1 weeks, suggesting the combination provided durable disease control, they added.

Safety was consistent with what was seen in a previous study of T-VEC and pembrolizumab in melanoma. In this sarcoma study, the incidence of grade 3 treatment-related adverse events was 20%, while in studies of conventional chemotherapy in this setting, the rate of those events has been “comparable but generally higher,” the investigators wrote.

Dr. Kelly and colleagues wrote that a randomized clinical trial is the “ideal next step” in the development of the regimen, adding that an expansion of the present phase 2 study is in progress.

The study was funded by Amgen and Merck, with additional grant support from Cycle for Survival and the National Institutes of Health/National Cancer Institute. Dr. Kelly reported disclosures related to Merck, Amgen, Agios Pharmaceuticals, and Exicure. Her coauthors reported disclosures with Regeneron, Novartis, Takeda, and Nektar, among others.

SOURCE: Kelly CM et al. JAMA Oncol. 2020 Jan 23. doi: 10.1001/jamaoncol.2019.6152.

Recommended Reading

Conference Coverage: ASCO 2019
MDedge Hematology and Oncology
Adolescent and young adult (AYA) survival trends
MDedge Hematology and Oncology
Overcoming barriers to clinical trial enrollment in patients with bone and soft tissue sarcoma: a paradigm for an increasingly heterogeneous cancer population
MDedge Hematology and Oncology
Becoming the paradigm for clinical trial enrollment
MDedge Hematology and Oncology
Metastatic angiosarcoma arising in a patient with long-standing treatment-refractory hemangioma
MDedge Hematology and Oncology
Pexidartinib Receives Category 1 Recommendation from NCCN
MDedge Hematology and Oncology
FB Support Groups Enable Rapid Access to Large Numbers of Patients With Rare Disease
MDedge Hematology and Oncology
Scientific Roundtable Focuses Efforts on Leiomyosarcoma Research
MDedge Hematology and Oncology
FDA Awards Grant To Study Temozolomide in Gist
MDedge Hematology and Oncology
FDA approves avapritinib for adults with GIST with PDGFRA mutation
MDedge Hematology and Oncology