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Tumor Microenvironment Gene Engineering with LOAd703 in Patients with Solid Malignancies: LOKON002 Phase I/IIb

Amanda Hahn1,2, Sandra Irenaeus1,2, Linda C Sandin3

  • 1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 29, 2026
PubMed
Abstract

Insights

LOAd703, a novel gene therapy, showed tolerability and inflamed tumors in advanced cancer patients. This approach led to long-term disease stabilization in some, warranting further investigation.

Area of Science:

  • Oncology
  • Gene Therapy
  • Immunotherapy

Background:

  • Advanced cancers present poor prognoses, necessitating novel therapeutic strategies.
  • The tumor microenvironment (TME) plays a critical role in cancer progression and treatment resistance.
  • Targeting immune pathways within the TME offers a promising avenue for cancer treatment.

Purpose of the Study:

  • To evaluate the tolerability, response activity, and TME-modulating capacity of LOAd703.
  • LOAd703 is a gene engineering viral vector designed to target CD40 and 4-1BB pathways.
  • Assess the potential of LOAd703 to overcome immune suppression in the TME.

Main Methods:

  • A phase I/IIb open-label, single-arm clinical trial (NCT03225989) was conducted.
  • Patients received up to eight intratumoral injections of LOAd703 biweekly, combined with gemcitabine-based chemotherapy.
  • Dose escalation followed a 3+3 design, with expansion at the two highest dose levels.

Main Results:

  • Forty-one patients with pancreatic, colorectal, ovarian, and biliary cancers were enrolled.
  • LOAd703 was generally well-tolerated, with common adverse events including pyrexia, chills, and fatigue (mostly grade 1-2).
  • Overall response rates varied by dose (0% to 25%), with a 35% ORR in first-line pancreatic cancer patients. Significant upregulation of Th1 immunity biomarkers was observed in the TME.

Conclusions:

  • Gene engineering of the TME with LOAd703 demonstrated the ability to inflame immune-cold tumors.
  • Long-term disease stabilization was observed in several patients treated with LOAd703.
  • Further research combining LOAd703 with chemotherapy and/or checkpoint inhibitors is recommended.

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