delolimogene mupadenorepvec (LOAd703) / Lokon - LARVOL DELTA

LOAd703 and chemotherapy combination in pancreatic cancer: insights from the LOKON001 study. (PubMed, Transl Gastroenterol Hepatol) - No abstract available

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Intravesical instillation of a TME engineering viral vector increases survival in an orthotropic bladder cancer model (AACR 2025) - "Non-muscle invasive urinary bladder cancer is currently treated with bacillus Calmette-Guérin (BCG) instillations followed by nadofaragene firadenovec-vncg for BCG refractory patients...We hypothesize that LOAd703, the human equivalent to Adm703, may be an interesting option for these patients...In conclusion, TME gene engineering with TMZ-CD40L and 4-1BBL increased survival of mice with orthotopic bladder cancer. Further studies investigating Adm703's effect on the immune system are planned."

Preclinical • Viral vector • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD40LG

LOKON001: LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=51 | Active, not recruiting | Sponsor: Lokon Pharma AB | Recruiting ➔ Active, not recruiting | Trial primary completion date: Oct 2024 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Lokon Pharma receives FDA Fast Track Designation for LOAd703 for the treatment of Pancreatic Cancer [Google translation] (Mynewsdesk) - "Lokon Pharma AB...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the company´s product candidate LOAd703 for the treatment of pancreatic cancer."

Fast track • Pancreatic Cancer

Lokon Pharma Announces Collaboration to Combine its TME Gene Engineering Product with Anti-PD-1 Antibody Tislelizumab in Pancreatic Cancer [Google translation] (Mynewsdesk) - "Lokon Pharma AB has initiated a clinical collaboration to combine in a randomized Phase 2 trial Lokon’s tumor microenvironment (TME) gene engineering product, LOAd703, with BeiGene’s anti-PD-1 antibody tislelizumab in patients with pancreatic cancer."

Commercial • Pancreatic Cancer

LOKON002: Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer (clinicaltrials.gov) - P1/2 | N=47 | Completed | Sponsor: Lokon Pharma AB | Active, not recruiting ➔ Completed

Oncolytic virus • Trial completion • Biliary Cancer • Colorectal Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

Tumor stroma inflammation and a systemic inflammatory response confirmed in patients treated with intratumoral tumor microenvironment gene engineering (LOKON002 trial) (SITC 2024) - P1/2 | "Methods Patients received intratumoral injections of LOAd703 (maximum 8 doses, dose escalation 3+3 design followed by dose confirmation cohorts) combined with standard-of-care chemotherapy (n=63%) or immune-conditioning gemcitabine (n=37%) for patients who had received established treatments. Ethics Approval The trial was approved by the regional ethical committee in Uppsala (Dnr 2017/327). All patients gave informed consent before taking part in the trial."

Biomarker • Clinical • Stroma • Tumor microenvironment • Biliary Cancer • Oncology • Solid Tumor • CD40LG • TGFB1

Novel gene therapy in advanced solid malignancies: A phase I/II clinical trial (ESMO 2024) - P1/2 | "All patients who experienced partial response had pancreatic cancer and received LOAd703 combined with gemcitabine and nab-paclitaxel. Indication of clinical benefit in a subset of patients combined with tolerability warrant further investigation of LOAd703."

Clinical • Gene therapy • Metastases • P1/2 data • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CD40LG

A phase I/II trial (LOKON003) evaluating tumor microenvironment (TME) gene engineering using a viral vector combined with atezolizumab in advanced malignant melanoma (ESMO 2024) - P1/2 | "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."

Biomarker • Metastases • P1/2 data • Tumor microenvironment • Viral vector • Melanoma • Oncology • Solid Tumor • CD40LG

Immunostimulatory gene therapy co-expressing immune activators TMZ-CD40L and 4-1BBL with a PD-L1-targeting Affibody molecule to reactivate T cell immunity (AACR 2024) - "Next, an adenovirus vector containing trimerized-CD40L and 4-1BBL (LOAd703), known to upregulate PD-L1 in stimulated dendritic cells, was modified to co-express the anti-PD-L1 Affibody molecule (LOAd724)...In summary, Affibody molecules can be expressed from adenoviral gene vehicles alone or in combination with immunostimulatory genes. Further studies are warranted to understand the role of local PD-L1 blockade in the tumor microenvironment following LOAd724 therapy."

Gene therapy • IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • CD40LG • PD-L1

LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study. (PubMed, Lancet Oncol) - P1/2 | "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."

Gene therapy • Journal • Metastases • Oncolytic virus • P1/2 data • P2 data • Cardiovascular • Diabetes • Fatigue • Gastrointestinal Cancer • Gene Therapies • Hematological Disorders • Hepatology • Hypertension • Leukopenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40LG • CD8

Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer (clinicaltrials.gov) - P1/2 | N=46 | Active, not recruiting | Sponsor: Lokon Pharma AB | Trial completion date: Dec 2024 ➔ Aug 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2023

Oncolytic virus • Trial completion date • Trial primary completion date • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma (clinicaltrials.gov) - P1/2 | N=26 | Completed | Sponsor: Lokon Pharma AB | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jul 2023 | Trial primary completion date: Dec 2023 ➔ Jul 2023

Combination therapy • Trial completion • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

A phase I/II study of LOAd703, a TMZ-CD40L/4-1BBL-armed oncolytic adenovirus, combined with nab-paclitaxel and gemcitabine in advanced pancreatic cancer. (ASCO 2022) - P1/2 | "Funded by: Pharmaceutical/Biotech Company. Combining intratumoral injections of LOAd703 with standard nPG chemotherapy was safe and feasible. The target response rate at the highest dose level was met, and treatment-emergent immune responses were observed. A follow-up clinical trial combining LOAd703, nPG, and the anti-PDL-1 inhibitor atezolizumab is underway."

Oncolytic virus • P1/2 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40LG

Oncolytic Cell-Based Therapy to Overcome Virus Inactivating Immune Response in Small Cell Lung Cancer Models (ASGCT 2023) - "Through in vitro and in vivo models of humoral immunity-mediated virus inactivation, NSCs.LOAd703 maximized the effect of OV by multiplying the infectious virus particles. They also minimized the blockage of the therapeutic effect of oncolytic viruses (OVs) by the immune barriers and thus protected the OVs from immune mediated inactivation and therefore enhanced the anti-cancer effects."

Preclinical • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma (clinicaltrials.gov) - P1/2 | N=26 | Active, not recruiting | Sponsor: Lokon Pharma AB | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Immunostimulatory gene therapy targeting CD40/4-1BB in combination with chemotherapy induces an inflammatory gene profile in tumors from patients with advanced disease (AACR 2023) - P1/2 | "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."

Clinical • Combination therapy • Gene therapy • IO biomarker • Metastases • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CCL2 • CCR7 • CD14 • CD163 • CD40 • CD40LG • CD8 • CD80 • CD86 • CXCL10 • CXCL8 • IFNG • IL15 • IL6 • ITGAM • NCAM1 • PD-1 • TAP1

A phase I/II clinical study of an oncolytic adenovirus expressing the immunostimulatory transgenes TMZ-CD40L and 4-1BBL in advanced solid malignancies (AACR 2023) - P1/2 | "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."

Clinical • Metastases • Oncolytic virus • P1/2 data • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CD40LG

Immunostimulatory gene therapy with an oncolytic virus expressing TMZ-CD40L and 4-1BBL induces oncolysis and show immunomodulatory capacity in soft tissue sarcoma (AACR 2023) - "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."

Gene therapy • Immunomodulating • IO biomarker • Oncolytic virus • Melanoma • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD40LG • CD46

Immunostimulatory gene therapy with oncolytic viruses potentiates the effect of paclitaxel and cisplatin in ovarian cancer (AACR 2023) - P1/2 | "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)."

Gene therapy • IO biomarker • Oncolytic virus • Oncology • Ovarian Cancer • Solid Tumor • CD40LG

Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer (clinicaltrials.gov) - P1/2 | N=46 | Active, not recruiting | Sponsor: Lokon Pharma AB | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ Dec 2024 | Trial primary completion date: Mar 2023 ➔ Dec 2023

Enrollment closed • Oncolytic virus • Trial completion date • Trial primary completion date • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC) (clinicaltrials.gov) - P1/2 | N=94 | Terminated | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2022 ➔ Sep 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Sep 2022; The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.

Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=55 | Recruiting | Sponsor: Lokon Pharma AB | Trial completion date: Dec 2021 ➔ Oct 2025 | Trial primary completion date: Oct 2021 ➔ Oct 2024

Oncolytic virus • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC) (clinicaltrials.gov) - P1/2 | N=94 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | N=382 ➔ 94 | Trial completion date: Nov 2023 ➔ Dec 2022 | Trial primary completion date: May 2023 ➔ Dec 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Induction of tumor cell apoptosis & immunogenic cell death by CD40L-armed oncolytic adenoviruses (AACR 2022) - "Here we have evaluated the anti-tumor effects of trimerized membrane-bound (TMZ)-CD40L-armed LOAd700 and TMZ-CD40L/4-1BBL-armed LOAd703 in a variety of solid tumors to understand the underlying tumor modulating mechanisms. Upregulation of cell surface calreticulin as well as the death receptors TRAIL-R1 and -R2 indicated generation of a more immunogenic phenotype of cancer cells. Thus, our findings suggest that CD40L-armed LOAd viruses could be inducers of apoptosis and immunogenic cell death in a variety of cancer types with an augmented effect in cancer cells expressing the CD40 receptor."

Immunogenic cell death • IO biomarker • Oncolytic virus • Oncology • Solid Tumor • CALR • CASP3 • CASP7 • CD40LG • HSP90AA1 • TNFRSF10A • TNFRSF10B