988O - A phase I/II trial (LOKON003) evaluating tumor microenvironment (TME) gene engineering using a viral vector combined with atezolizumab in advanced malignant melanoma

Background

LOAd703 (delolimogene mupadenorepvec) is a tumor microenvironment (TME) gene engineering adenovirus encoding trimerized CD40L and 4-1BBL designed to cause stroma inflammation and subsequent anti-tumor immunity. Checkpoint inhibitor (CPI) therapy has shown benefit in overall survival (OS) in advanced malignant melanoma (MM). However, a majority of patients have shown primary resistance or eventually experienced progressive disease on CPI therapy. In this phase I/II trial, we aimed to re-sensitize CPI refractory MM with the addition of LOAd703 to atezolizumab (anti-PD-L1).

Methods

Patients were recruited between 2020 and 2023 inSweden and the United States to the study sponsored by Lokon Pharma. LOAd703 (intratumoral; 1x10¹¹ or 5x10¹¹ viral particles, up to 12x) and atezolizumab (intravenously; 1200 mg, up to 19x) were administered every third week. Patients were evaluated for safety (CTCAE), immune response, OS and objective response (RECIST 1.1).

Results

All recruited patients (n=24) had stage IV MM and had received a median of 2 prior lines of systemic treatment including adjuvant (range 1-6). Twelve of the patients had elevated LDH at screening. Treatments with LOAd703 were generally well tolerated. Most common adverse events with suspected relationship to LOAd703 were pyrexia (n=14 patients), vomiting (n=5), and chills (n=5). Serious adverse events related to LOAd703 were Grade 2 fever (n=1) and Grade 2 cytokine release syndrome (n=1). Immune responses are under evaluation and will be presented at the meeting. Table: 988O

Survival and response data

Conclusions

LOAd703 TME gene engineering combined with atezolizumab was well tolerated. Objective responses and durable SDs were observed in patients with immunotherapy refractory advanced malignant melanoma, showing the additive effect of LOAd703 to atezolizumab. The median OS is encouraging and not yet reached for the highest dose cohort.

Clinical trial identification

NCT04123470; January 28, 2020.

Editorial acknowledgement

Legal entity responsible for the study

Lokon Pharma.

Funding

This study was funded by Lokon Pharma, and by grants to G. Ullenhag and V. Rydén from The Research Foundation Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond and Uppsala University Hospital (ALF), to G.J. Ullenhag from the Swedish Cancer Society, and to A. Loskog from the Swedish Research Council and the Swedish Cancer Society. F. Hoffmann-La Roche and Lokon Pharma had a supply agreement for atezolizumab.

Disclosure

L.C. Sandin, E. Eriksson, J. Leja Jarblad: Financial Interests, Personal, Full or part-time Employment: Lokon Pharma. A. Loskog: Financial Interests, Personal, Full or part-time Employment: Lokon Pharma; Financial Interests, Personal, Member of Board of Directors: Lokon Pharma, Repos Pharma, Vivolux, Aros Biotech, Tanea Medical, Almoalo, Nexttobe, Promgranate Veterinarian; Financial Interests, Personal, Leadership Role: Lokon Pharma, Lynxalo; Financial Interests, Personal, Licencing Fees or royalty for IP, Royalty for IP: Lokon Pharma. All other authors have declared no conflicts of interest.