Introduction: The results of the phase 2 IGNYTE trial showed that in patients with non-melanoma skin cancer (NMSC), RP1 and nivolumab (Opdivo) therapy were good.
The results of the Phase 2 IGNYTE trial (NCT03767348), presented at the 2022 Multidisciplinary Head and Neck Cancer Symposium, showed that in patients with non-melanoma skin cancer (NMSC), RP1 and nivolumab (Opdivo) treatment produced a good antitumor response and was well tolerated and safe.
Patients with cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), Mekell cell carcinoma (MCC), and angiosarcoma achieved at least partial remission (PR) with combination therapy.
Dr Jiaxin Niu from Banner MD Anderson Cancer Center said: "For CSCC, what makes us most happy is the significant complete response (CR) rate, which is as high as almost 50%. ”
The results of Niu's discussion came from the NMSC portion of the open-label, multicenter, Phase 1/2 IGNYTE trial in which patients received treatment with RP1 (an enhanced herpes simplex virus 1 (HSV-1)) plus navumab (an anti-PD-1 monoclonal antibody).
Niu explains: "Oncolytic viruses have long been studied in cancer immunotherapy, so the idea is to use this bioengineered virus because it can preferentially infect cancer cells and replicate in them, promoting immunogenic cell death." ”
At the time of evaluation in the IGNYTE trial, 30 PATIENTSC who had not received anti-PD-1 or anti-PD-L1 therapy received RP1 of 1×106 PFU/mL in the first dose of cycle 1, followed by RP1 of 1×107 PFU/mL in all subsequent doses, plus navumab at cycles 2 to 8 plus 240 mg of navumab every 2 weeks, and then received maintenance therapy with navuzumab.
Of these 30 patients, 15 had CSCC, 4 had BCC, 4 had MCC, and 5 had hemangiosarcoma. As of June 3, 2021, 9 patients with CSCC (60.0%), 1 patient with BCC (25%), 3 patients with MCC (75.0%), and 3 patients with hemangiosarcoma (60.0%) had objective remission. Only patients with CSCC achieved CR, while patients in other subtypes did not develop CR. PR was present in 2 patients with CSCC (13.2%), 1 patient with BCC (25.0%), 3 patients with MCC (75.0%), and 3 patients with hemangiosarcoma (60.0%). Four patients with CSCC (26.7%) and one patient with BCC, MCC, and angiosarcoma developed progressive disease, respectively.
The data showed that most patients experienced a deep response and that the duration of response was prolonged. Some patients are still in remission after 2 years of treatment. In addition, the median mitigation duration has not been reached at the data cutoff.
In terms of safety, most adverse events (AEs) are Grade 1 or Grade 2. All levels of AE developed in 59 patients (89.5%). One patient developed grade 4 and grade 5 AE, associated with nalvulamumab. Nineteen patients (27.5%) developed grade 3 or more AE, including fatigue, fever, and decreased appetite/diarrhea.
Navumab is a monoclonal antibody targeting PD-1, which relieves the immune mechanism by inhibiting the PD-1/PD-L1 pathway, enhances the anti-tumor immune response, thereby playing a role in tumor killing, which was first approved in the FDA in 2014 and has been approved for a variety of tumor treatment indications, including melanoma and non-small cell lung cancer.