delolimogene mupadenorepvec (LOAd703)

Collectively, the results propose that treatment with LOAd703 and atezolizumab induce an immune phenotype of ICI resistant patients that has previously been reported associative with ICI responsiveness. These results merits further clinical investigation of supplementary LOAd703 treatment to accomplish ICI sensitivity in ICI resistant MM.

LOAd703 was administered every 2 weeks by ultrasound-guided intratumoral injections, combined with a standard-of-care or immune-conditioning gemcitabine-based chemotherapy regimen. A trend of higher interferon-gamma (IFN-γ) plasma levels in the highest LOAd703 dose cohort was observed. The acceptable toxicity associated with LOAd703 and chemotherapy, combined with signs of clinical benefit in poor prognostic cancer patients, warrant further studies.

P1/2, N=51, Completed, Lokon Pharma AB | Active, not recruiting --> Completed

The small sample size and single arm design limits effect interpretation but the data shows promise for continued clinical investigation. Study registration: NCT04123470.

P1/2, N=51, Active, not recruiting, Lokon Pharma AB | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2024 --> Dec 2025

P1/2, N=47, Completed, Lokon Pharma AB | Active, not recruiting --> Completed

Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing.

P1/2, N=46, Active, not recruiting, Lokon Pharma AB | Trial completion date: Dec 2024 --> Aug 2024 | Trial primary completion date: Dec 2023 --> Aug 2023

In the LOKON002 phase I/II clinical trial (NCT03225989), therapy with LOAd703 (delolimogene mupadenorepvec) is investigated in combination with gemcitabine-based chemotherapy in patients with advanced cancer. In conclusion, LOAd703 therapy in combination with chemotherapy generated an inflamed tumor microenvironment in tumors that are normally seen as immunologically “cold”. Hence, LOAd703 may be able to prime tumors for immune checkpoint inhibitors or other immunotherapies, such as adoptive T or NK cell transfer.

Partial response (PR) was achieved in two patients with pancreatic cancer treated at the highest LOAd703 dose level in combination with gemcitabine and nab-paclitaxel. No association between adverse events and response was identified. Anti-adenoviral antibody levels (IgG), which increased in all patients, could not be related to indices of clinical benefit.Based on the safety of LOAd703 at all dose levels studied, as well as evidence of objective clinical activity in patients with advanced pancreatic cancer, further disease-directed studies of intratumoral administration of LOAd703 are warranted.

We are also performing multiplex analysis of proteomic changes in infected tumor cells using the OLINK® TARGET 96 assay. Finally, we willconfirm the effect of LOAd703 in vivo in a murine xenograft model for STS.

Ovarian cancer is commonly treated with debulking surgery, followed by a combination of a taxane and a platinum-based chemotherapy. This effect was confirmed in vivo, in which the combination therapy had a better tumor control than the other treatment groups. A clinical trial is ongoing to confirm the effect of adding LOAd703 to different treatment regimes in ovarian cancer (NCT03225989).