989O - Novel gene therapy in advanced solid malignancies: A phase I/II clinical trial

Background

Despite the success of cancer immunotherapy there are still tumor types in need of novel approaches. LOAd703 is an oncolytic adenovirus serotype 5/35 expressing the immunostimulatory transgenes trimerized membrane-bound CD40L and 4-1BBL. Safety and efficacy of LOAd703 and concomitant chemotherapy were evaluated in an open-label bi-center phase I/II clinical trial.

Methods

Patients were treated bi-weekly with maximum eight ultrasound-guided intratumoral injections of LOAd703 combined with either standard of care chemotherapy or conditioning gemcitabine. Increasing doses of LOAd703 (5x10¹⁰ viral particles: VP, 1x10¹¹ VP and 5x10¹¹ VP) were evaluated in phase I according to a standard 3+3 design. Tolerability of the highest dose in phase I was confirmed in phase Iia. Phase Iib was conducted to compare the highest dose levels.

Results

41 patients with pancreatic cancer (n = 29), colorectal cancer (n = 5), ovarian cancer (n = 4) and biliary cancer (n = 3) were included. The number of previous treatment lines varied between 0 and 5. 63% received LOAd703 with standard of care chemotherapy and the remaining 37% received conditioning gemcitabine. 22% experienced clinical benefit with partial response (n = 6) or long-lasting stable disease (≥ 5 months, n = 3). All patients who experienced partial response had pancreatic cancer and received LOAd703 combined with gemcitabine and nab-paclitaxel. This subset of patients showed a response rate of 32% and a median survival of 7.3 months. Two patients treated with LOAd703 and conditioning gemcitabine experienced long-lasting stable disease. Adverse events associated with LOAd703 and related procedures were overall transient and of grade 1-2. The most frequent adverse events were pyrexia (76%), chills (39%), and fatigue (34%). However, three patients developed nephrotoxicity possibly related to LOAd703. There was no correlation between serum anti-adenovirus IgG antibodies, which increased in all patients, and clinical benefit. Immune responses are under evaluation and will be presented at the meeting.

Conclusions

Indication of clinical benefit in a subset of patients combined with tolerability warrant further investigation of LOAd703.

Clinical trial identification

NCT03225989.

Editorial acknowledgement

Legal entity responsible for the study

Lokon Pharma AB.

Funding

Lokon Pharma AB.

Disclosure

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