LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer

NCT02705196 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: LOKON001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to see if LOAd703 (an oncolytic adenovirus) can be safely given to patients with pancreatic cancer. The study will also evaluate whether or not intratumoral injection of LOAd703 will support current standard of care treatment to reduce the size of the tumor and improve survival of the patients. Adenoviruses are known as the "common cold" virus and most individuals have had multiple infections during their lifetime. Oncolytic adenoviruses are adenoviruses that are modified so they cannot multiply and spread (known as replicating) properly in normal (e.g. healthy) cells, but instead, they infect and replicate very well in cancer cells. This strong replication leads to the death of the cancer cell. Oncolytic viruses have been evaluated in multiple clinical trials for cancer treatment during the past decade and been proven safe. It is common to have a fever the first day or two after virus injection since the immune system will react to the virus infection. The immune system can also kill cancer cells but to do so it needs to be properly stimulated. Oncolytic viruses alone do not seem to be strong enough to activate clinically relevant anti-cancer responses. However, it is thought that if additional immune system stimulators are added to the oncolytic viruses they may be able to result in clinical relevant antic-cancer responses. LOAd703 is an oncolytic adenovirus that has been modified to include additional immune system stimulators. Specifically, genes that stimulate the immune system have been added to the oncolytic adenovirus. Once the oncolytic adenovirus infects the cancer cells, the genes will be expressed, resulting in activation of the immune response so it can attack and kill cancer cells. In this study, LOAd703 will be given by intratumoral injections. It will be given in addition to standard of care treatment with gemcitabine and nab-paclitaxel +/- the anti-PD-L1 antibody atezolizumab. Because this is an experimental therapy, there will be extra visits for disease monitoring and samples accordingly to the detailed information below. The LOAd703 is an investigational agent not approved by the FDA.

Conditions

Pancreatic Cancer

Keywords

oncolytic; adenovirus; pancreatic; cancer; LOKON; LOAd703

Outcome Measures

Primary Outcomes (1)

• Number of patient with dose-limiting toxicities (DLTs) as evaluated accordingly to CTCAE 4.0

  Maximum tolerated dose of multiple (6x) image-guided intratumoral injections of LOAd703 at three dose levels in combination with standard of care therapy

  9 months

Secondary Outcomes (2)

• Overall Response Rate

  9 months

• Overall Survival

  6 months post last patient, last visit

Study Arms (2)

Arm 1 Intratumoral LOAd703

EXPERIMENTAL

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment. The following LOAd703 doses will be evaluated: Dose level 1: 5 X 10\^10 viral particles per treatment Dose level 2: 1 X 10\^11 viral particles per treatment Dose level 3: 5 X 10\^11 viral particles per treatment

Genetic: delolimogene mupadenorepvec; Drug: gemcitabine; Drug: nab-paclitaxel

Arm 2: Intratumoral LOAd703 + atezolizumab

EXPERIMENTAL

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment. A fixed dose of atezolizumab 1680 mg will be given every 4 weeks on day 1 of each chemotherapy cycle. Patients will be assigned to the following LOAd703 doses: Dose level 1: 1 X 10\^11 viral particles per treatment Dose level 2: 5 X 10\^11 viral particles per treatment

Genetic: delolimogene mupadenorepvec; Drug: gemcitabine; Drug: nab-paclitaxel; Biological: atezolizumab

Interventions

delolimogene mupadenorepvec GENETIC

oncolytic virus encoding TMZ-CD40L and 4-1BBL

Also known as: LOAd703

Arm 1 Intratumoral LOAd703; Arm 2: Intratumoral LOAd703 + atezolizumab

gemcitabine DRUG

chemotherapy

Also known as: Gemzar

Arm 1 Intratumoral LOAd703; Arm 2: Intratumoral LOAd703 + atezolizumab

nab-paclitaxel DRUG

chemotherapy

Also known as: Abraxane

Arm 1 Intratumoral LOAd703; Arm 2: Intratumoral LOAd703 + atezolizumab

atezolizumab BIOLOGICAL

anti-PD-L1 antibody

Also known as: Tecentriq

Arm 2: Intratumoral LOAd703 + atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of ductal adenocarcinoma of the pancreas (PDAC).
• Low tumor burden with at least one lesion that is suitable for image-guided intratumoral injection and needle biopsy.
• The patient is not eligible for a complete surgical resection of their disease as evaluated by a radiologist and/or surgeon.
• Patients who may receive the injections endoscopically should be eligible for sedation.
• The patient must be eligible for standard of care treatment with gemcitabine +nab-paclitaxel.
• Age ≥ 18 yrs of age
• Females of childbearing potential must have a negative pregnancy test and agree to use contraception during on-study protocol treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
• Absolute neutrophil count (ANC) ≥1.0 x 10\^9/l, hemoglobin ≥9 g/dl, platelet count ≥ 100 x 10\^9/l, prothrombin (INR) \<1.5.
• Adequate hepatic function, with bilirubin \< 1.5 x the ULN, and AST and ALT \< 2.5 x ULN
• Adequate renal function with serum creatinine \<2 x the ULN or creatinine clearance \>30 mL/min
• The patient must provide informed consent.

You may not qualify if:

• Any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (\>10 mg/day of prednisone equivalence), lymphodepleting antibodies or cytotoxic agents.
• Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies such as alemtuzumab (Campath), or rapamycin/rapalogs or cytotoxic agents within 21 days of registration
• Treatment with biologic therapy within 21 days of registration.
• Use of any investigational agents within 21 days of registration.
• The use of systemic immunostimulatory agents (including, but not limited to, interferons and IL-2) are prohibited within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment and during study treatment because these agents could potentially increase the risk for autoimmune conditions when given in combination with atezolizumab
• Pregnant or breastfeeding females.
• Known active hepatitis B or C infection, HIV infection or tuberculosis.
• Patients with active autoimmune disease or immune deficiency or previous Guillain-Barre syndrome. Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible for the study provide all of the following conditions are met:
• Rash must cover \<10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled intercurrent illness including but not limited to psychiatric illness/social situations that in the opinion of the Investigator would compromise compliance of study requirements or put the patient at unacceptable risk.
• Other malignancies within the past 2 years (not including basal cell carcinoma of the skin, prostate cancer or in situ cervix carcinoma).
• Moderate to large volume ascites.
• History of leptomeningeal disease.

Sponsors & Collaborators

• Lokon Pharma AB: lead

Study Sites (2)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Baylor St Luke's Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Musher BL, Rowinsky EK, Smaglo BG, Abidi W, Othman M, Patel K, Jawaid S, Jing J, Brisco A, Leen AM, Wu M, Sandin LC, Wenthe J, Eriksson E, Ullenhag GJ, Grilley B, Leja-Jarblad J, Hilsenbeck SG, Brenner MK, Loskog ASI. 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. Lancet Oncol. 2024 Apr;25(4):488-500. doi: 10.1016/S1470-2045(24)00079-2.

  PMID: 38547893 DERIVED

Related Links

• Sponsors website

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenoviridae Infections; Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; atezolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Angelica Loskog, PhD

  Lokon Pharma AB

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: March 10, 2016
• Study Start: November 1, 2016
• Primary Completion: November 15, 2025
• Study Completion: November 15, 2025
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)