Robert Andtbacka, MD
Oncolytic immunotherapies are proving to be powerful agents for the treatment of melanoma, both as monotherapies and in combination with checkpoint inhibitors.
In October 2015, the FDA approved talimogene laherparepvec (T-VEC; Imlygic) for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. The approval was the first of its kind for the treatment of melanoma and was based on the phase III OPTiM study, which compared T-VEC to GM-CSF.
In the study, a durable response rate of 16.3% was seen with T-VEC compared with 2.1% for GM-CSF. The objective response rate (ORR) was 26.4% versus 5.7% and the complete response rate was 11% compared with 1% for T-VEC and GM-CSF, respectively.
T-VEC has also shown potential in combination with pembrolizumab (Keytruda), as well as in combination with ipilimumab (Yervoy).
Results from a phase Ib trial that were recently presented at the 2015 Society for Melanoma Research Congress showed that the ORR was 56.3% with the combination of pembrolizumab and T-VEC. Based on these findings, Merck and Amgen, the developers of T-VEC, are planning a phase III study for the combination in patients with regionally or distantly metastatic melanoma.
T-VEC given in combination with ipilimumab for patients with previously untreated, unresectable melanoma also shows promise. In a phase Ib study, the ORR for ipilimumab plus T-VEC was 56%, with 33% of patients experiencing a complete response. The disease control rate was 72%.
In addition to T-VEC, additional oncolytic immunotherapies are currently being investigated in combination with checkpoint inhibitors. HF10, a replication-competent HSV-1 oncolytic virus, is being given in combination with ipilimumab in patients with stage IIIb, IIIc, or IV unresectable or metastatic malignant melanoma in an ongoing phase II study.
Another ongoing phase Ib study is investigating the use of coxsackievirus A21 (CAVATAK), a causative agent of the common cold, in combination with pembrolizumab in patients with advanced melanoma for whom pembrolizumab would be considered standard of care.
The role of oncolytic immunotherapies continues to evolve in melanoma, says Robert Andtbacka, MD, an associate professor in the Division of Surgical Oncology, Department of Surgery at the University of Utah School of Medicine. OncLive
spoke with Andtbacka for a better understanding of what is on the horizon for the novel therapeutics.
OncLive: What role do oncolytic immunotherapies currently play in the treatment of melanoma?
: The past few years have been very exciting for the use of oncolytic immunotherapies. We have a number of clinical trials that have been completed and others that are currently ongoing. Some of these studies are examining how we are using these oncolytic immunotherapies. Often, we are injecting directly into the tumor to activate the immune system. We are using them as both monotherapies and as combinations.
Also, we are transitioning into using these in the neoadjuvant setting. Previously, it has really been with patients who primarily have had unresectable disease. However, it is now being studied in the neoadjuvant setting in patients who have resectable disease, but whom we know after surgery will have a very high risk of recurrence.
What role can oncolytic immunotherapies play in combating resistance?
Over the past year or so, we have really been able to show that oncolytic immunotherapies can change the tumor microenvironment. Many of our patients with melanoma who go on other therapies, specifically checkpoint inhibitors, do not always respond to those therapies. We often ask the question, “Why is this?” When we do biopsies in those patients who do not respond, we often find that they do not have tumor-infiltrating lymphocytes. Those lymphocytes need to be there in order for them to have a response to the checkpoint inhibitors. We have been able to inject into the lesions and show that we have a very robust change in the tumor microenvironment.