TILT-123 Shows Early Activity in Advanced Cancers – Renal and Urology News

TILT-123 (igrelimogene litadenorepvec) has demonstrated activity in heavily pretreated patients with advanced cancers in a phase 1 trial, according to researchers. They reported these findings in Clinical Cancer Research.

TILT-123 is an “oncolytic adenovirus armed with tumor necrosis factor alpha and interleukin-2, designed to induce T-cell infiltration and cytotoxicity in solid tumors,” the researchers explained.

They tested TILT-123 in the phase 1 TUNIMO trial (ClinicalTrials.gov Identifier: NCT04695327). The trial included 20 patients with advanced solid tumors for whom standard therapy had failed or did not exist.

The patients had sarcoma (n=7), melanoma (n=3), ovarian/peritoneal cancer (n=3), head and neck cancer (n=2), HER2-positive breast cancer (n=1), non-small cell lung cancer (n=1), anaplastic thyroid carcinoma (n=1), appendiceal cancer (n=1), and neuroendocrine carcinoma of the bladder (n=1). They had received a median of 4.5 prior lines of therapy (range, 1-15).

Patients received intravenous TILT-123 on day 1 and intratumoral TILT-123 on days 8, 22, 36, 48, and 64. TILT-123 was detected in the blood 1 hour after intravenous and intratumoral dosing. The researchers noted that the viral amount generally fell below the level of quantification 16 hours after treatment. However, 1 patient had detectable virus in the blood 7 days after intravenous treatment, and this patient was among the longest survivors (377 days).

There were no dose-limiting toxicities. The most common adverse events were fever (16.5%), chills (12.8%), and fatigue (8.3%). There were 3 grade 4 treatment-related events (1 case each of thrombocytopenia, neutropenia, and lymphopenia).

The researchers evaluated the antitumor efficacy of TILT-123 in both injected and non-injected tumors. Disease control was observed in 9 of 19 injected tumors assessed via CT and in 11 of 17 injected tumors assessed via PET. Disease control was also seen in 9 of 13 non-injected tumors assessed via CT and in 11 of 14 non-injected tumors assessed via PET.

The median progression-free survival was 87.5 days for the entire cohort, 181 days for patients with disease control, and 65 days for patients without disease control (P <.0001).

The median overall survival was 124.5 days for the entire cohort, 213.5 for patients with disease control, and 109 days for patients without it (P =.165).

There were 4 patients who were still alive more than 1 year after trial enrollment, and 3 of them were still alive more than 600 days after enrollment. They had myxoid liposarcoma, anaplastic thyroid carcinoma, leiomyosarcoma, and nodular melanoma.

“[T]ILT-123 was safe and able to produce favorable clinical and immunological antitumor effects in this difficult-to-treat patient demographic,” the researchers wrote. “Keeping in mind that TILT-123 was developed for activating T cells, it will be interesting to see the results of combination therapies with synergistic approaches such as checkpoint inhibitors and adoptive cell therapy with tumor-infiltrating lymphocytes.”

Disclosures: This research was supported by TILT Biotherapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor