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Intratumoral therapy increases response to checkpoint inhibitor for melanoma

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The phase 2 registration trial designed to evaluate ImmunoPulse IL-12 in combination with pembrolizumab for unresectable metastatic melanoma showed an increase in response rates among patients who were not expected to respond to anti–PD-1 therapy alone.

ImmunoPulse IL-12 (OncoSec Medical) is an intratumoral immunotherapy platform that delivers DNA-based interleukin-12.

Alain Algazi

The single-arm, open-label trial evaluated the combination of ImmunoPulse IL-12 with pembrolizumab (Keytruda, Merck), a PD-1 checkpoint inhibitor, in patients with stage III/IV melanoma who had a low likelihood of responding to an anti–PD-1 therapy based on their tumor biomarkers (CD8–positive tumor infiltrating lymphocytes < 22% PD-1^hiCTLA-4⁺).

Key endpoints included best overall response rate, safety and tolerability, duration of response, 24-week landmark PFS, median PFS and OS.

Patients treated with the combination demonstrated an ORR of 43% at 24 weeks and best ORR of 48%.

In total, 24% of patients achieved complete response, 19% had partial response and 9% demonstrated stable disease, for a total disease control rate of 52%.

The combination demonstrated a favorable safety profile and was well tolerated.

“Collectively, these data suggest that intratumoral IL-12 DNA with electroporation in combination with pembrolizumab can effectively alter the tumor microenvironment by triggering adaptive resistance,” study researcher Alain Algazi, MD, skin cancer specialist in the Melanoma Center at UCSF Helen Diller Family Comprehensive Cancer Center, said in a company-issued release. “This increases the substrate for a therapeutic PD-1/PD-L1 blockade while driving systemic antitumor immunity and concordant clinical responses in patients unlikely to benefit from anti–PD-1 monotherapy.”

Further, nine of the patients had been previously treated with checkpoint inhibitor therapy. This subset demonstrated a 33% ORR with the combination.

Analysis of the biomarker data suggested the combination “is transforming ‘cold’ tumors, which would be predicted to not respond to anti–PD-1 therapy, into ‘hot’ tumors, thus increasing the potential for a meaningful clinical response to the checkpoint inhibitor therapy,” the release said.

Results were presented at the ASCO-SITC Clinical Immuno-Oncology Symposium in Orlando.

A phase 2 registration study, expected to begin this year, will evaluate the combination of ImmunoPulse IL-12 and an anti–PD-1 therapy in patients with melanoma who have previously failed an approved anti–PD-1 therapy alone.

“OncoSec’s vision to bring intratumoral gene therapies to the oncology market continues to advance with these positive, impactful data, which hold immense promise for cancer patients who are unlikely to benefit from immunotherapy,” Punit Dhillon, president and CEO of OncoSec, said in the release. – by Kristie L. Kahl

Reference:

Algazi AP, et al. Abstract 78. Presented at: ASCO-SITC Clinical Immuno-Oncology Symposium; Feb. 24-26; Orlando, Fla.