HF10 plus Ipilimumab Increases Response Rates in Metastatic Melanoma
When combined with systemic ipilimumab (Yervoy), the investigational oncolytic viral immunotherapy HF10, a mutation of the HF strain of the herpes simplex virus type 1 (HSV-1), has local and systemic activity in patients with metastatic melanoma, said Robert Andtbacka, MD, CM, Huntsman Cancer Institute, Salt Lake City, during a poster presentation at the 2016 American Society of Clinical Oncology meeting. He added that HF10 substantially improves the response rate of ipilimumab alone and does not exacerbate ipilimumab toxicity.
In a phase 2 clinical trial, 46 patients (median age, 67 years) with stage IIIB, IIIC, or IV unresectable or unresected metastatic melanoma received intratumoral injections of HF10 in combination with intravenous infusions of ipilimumab. Overall, 65% of the participants had HSV-1 antibody.
The primary overall response rate (ORR) at 24 weeks was 40%. Changes in maximal tumor burden included complete response in 12% of patients, partial response in 28% of patients, stable disease in 25% of patients, clinical benefit (complete response plus partial response plus stable disease) in 65% of patients, and progressive disease in 30% of patients. An analysis after 24 weeks showed a trend toward increasing responses, with 14% complete response and 35% partial response (49% ORR). Responses were observed in 8 (53%) of the patients with stage IV melanoma.
Because approximately 50% of the patients had received previous therapy, Dr Andtbacka observed that these findings are especially impressive.
Grade ≥3 toxicities were generally associated with ipilimumab. Although all patients had some treatment-emergent adverse events, grade ≥3 adverse events related to HF10 therapy were reported in only 4 (9%) patients, and none of the patients discontinued treatment because of these events. Adverse events were consistent with those reported for other oncolytic viruses, such as grade ≤2 chills, fatigue, headache, injection-site reactions, malaise, nausea, and pruritus.
“Preliminary efficacy evaluation suggests HF10 plus ipilimumab has both local and systemic antitumor activity and substantially improves the response rate of ipilimumab alone and does not exacerbate ipilimumab toxicity. Intratumoral HF10 serial injections are safe and well-tolerated in combination with ipilimumab and are a potential novel therapeutic approach for metastatic melanoma,” concluded Dr Andtbacka.
Additional Studies on Intralesional Therapies
Dr Andtbacka discussed 2 additional studies that are investigating the use of intralesional therapies in combination with other modalities in metastatic melanoma.
One study involved patients with metastatic melanoma who did not have a complete response with the chemoablative agent PV-10; the study researchers evaluated adding radiotherapy to PV-10 injections. In this Australian study led by Matthew C. Foote, MD, Princess Alexandra Hospital, Brisbane, 13 patients (mean age, 69 years) received 30 Gy (6 fractions of 5 Gy twice weekly for 3 weeks) of 3-dimensional conformal radiotherapy (photons or electrons) starting 6 to 10 weeks after injections of PV-10.
The ORR after a median follow-up of 19.3 months was 87% (complete response, 33%; partial response, 53%), with complete responses lasting a mean of 12.2 months. Complete responses were more likely with metastases <10 mm in diameter. The treatment was well-tolerated.
“We see that adding radiation, in this small series, led to improved responses,” Dr Andtbacka said.
Finally, Dr Andtbacka discussed intralesional therapy with a second investigational oncolytic virus, coxsackievirus (CVA) 21. He noted that in patients for whom treatment with ipilimumab, pembrolizumab (Keytruda), or nivolumab (Opdivo) was not effective, biopsies showed very few tumor-infiltrating lymphocytes. However, after only 3 injections of CVA21, there was a very robust increase in tumor-infiltrating lymphocytes, including CD8+ T-cells.