ONCOS-102 Plus Pembrolizumab Induces Impressive Responses in Anti-PD1–Refractory Melanoma

The combination of ONCOS-102 plus pembrolizumab (Keytruda) demonstrated promising objective responses as treatment of patients with anti-PD1–refractory malignant melanoma in a phase 1 clinical trial, announced Targovax in a press release.

Tumor responses were observed in 7 of 20 evaluable patients, which translated to an objective response rate (ORR) of 35% by RECIST 1.1 criteria. Multiple examples of responses were observed in non-injected lesions as well, including 2 patients where a non-injected lesion disappeared completely. These data suggest that ONCOS-102 may induce systemic anti-tumor immunity.

“Checkpoint inhibitors have had a significant impact on the way we treat melanoma; however, a subset of patients still does not respond or become resistant to treatment. Therefore, there is a high medical need for immune-activating agents to overcome resistance to checkpoint blockade. ONCOS-102 is one such agent that can re-sensitize patients to anti-PD1 therapy,” said Jedd Wolchok, investigator, Memorial Sloan Kettering Cancer Center, in a statement. “Although these are early data, observing objective responses with some occurring in non-injected lesions in this first exploratory phase 1 trial is encouraging, and we will follow with great interest as ONCOS-102 moves forward into later-stage development.”

The 2-part open-label study (NCT03003676) evaluated the role of this combination as treatment of patients with advanced, unresectable melanoma who have had disease progression despite treatment with an anti-PD1 checkpoint inhibitor. This patient population is particularly challenging to treat as they are resistant to approved immunotherapies and have limited treatment alternatives available.

In part 1 of the study, 3 intra-tumoral ONCOS-102 injections were administered in 9 patients during the first week, which was followed by systemic therapy with pembrolizumab every third week for up to 24 weeks.

Part 2 enrolled 12 patients who received a dosing regimen of 12 intra-tumoral ONCOS-102 injections; 4 injections were given during the first 2 weeks and were followed by concomitant ONCOS-102 administration and pembrolizumab every third week from week 3 up to 24 weeks.

Preliminary tumor responses were observed in 3 of the 9 patients in Part 1 of the study. One patient had been determined as non-evaluable due to not meeting the inclusion criteria, and 2 additional patients with ORR have been excluded as well.

Four patients in Part 2 achieved a tumor response in at least 1 CT scan. Patients in this part of the study also had markedly advanced disease. The majority of patients had stage IV metastatic melanoma when they entered the study.

Overall, both regimens from the study had favorable tolerability profiles. Neither regimen had safety concerns in the study.

The response rate of this therapy and its effect on non-injected lesions may be considered class-leading for the treatment of this patient population.

The primary end point of the trial is the incidence of treatment-emergent adverse events, and secondary end points include ORR, progression-free survival, and clinical benefit rates, as well as changes in immune cell subsets in tumor tissue before and after treatment and in the peripheral blood before and after treatment. Other key outcome measures include somatic mutational rate, changes in T cell receptor clonality in infiltrating and circulating T cells, and gene expression changes.

To be included in the study, patients had to be 18 years or older, have an ECOG performance status of 0 or 1, measurable disease according to RECIST 1.1, and acceptable coagulation status. They also had to have acceptable hematological function and liver and renal functions, as well as clinical stability of brain metastases for at least 4 weeks prior to the first day of therapy on study. Patients were excluded if they had any symptomatic autoimmune disease, any prior severe adverse events attributed to prior anti-PD-1 therapy that might contraindicate pembrolizumab, or a known active infection of Hepatitis B virus, Hepatitis C virus, or HIV.

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_{Targovax announces impressive objective responses as well as effects on non-injected lesions in ONCOS-102 trial in anti-PD1 refractory melanoma patients. News Release. Targovax. December 1, 2020. Accessed December 2, 2020. https://prn.to/3ltmvv7}