Our goal is to advance Photodynamic Therapy (PDT) as an adjuvant treatment for patients with non-small cell lung cancer (NSCLC) and other thoracic malignancies. With DigiLum™ controlled light dosimetry, thoracic surgeons will be able to activate a photosensitizer drug to precisely administer PDT to reduce disease spread and enhance antitumor immunity.
PDT is a two-stage cancer treatment that involves a photosensitizer drug that preferentially collects within cancer cells and then produces cell death and tumor structural change upon light activation. PDT has been shown to significantly improve patient progression-free and overall survival when applied intraoperatively following surgical lung cancer tumor resection. In pre-clinical studies PDT has also been shown to alter the contexture of tumors to make them more receptive to immunotherapy. PDT is safe even when combined with other adjunctive therapies and can be repeated without additive side effects or loss of efficacy. PDT presents minimal normal tissue toxicity, negligible systemic effects, lack of resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects. The dose and administration of PDT can be tailored to promote cell necrotic, apoptotic, and immune modulating effects.
Lumeda is pursuing two preliminary indications for the product- an adjuvant applied intraoperatively following NSCLC tumor resection and an immune-modulating treatment to elicit antitumor response.
Clinical studies are scheduled to start in 2021 and will investigate safety and provide an initial assessment of PDT effectiveness for each indication.
INTRAOPERATIVE ADJUVANT THERAPY
Of new lung cancer cases, 84% are non-small cell lung cancer (NSCLC). Of these cases, an estimated 30% are surgical candidates in which tumor resection, which can be curative, is the primary standard of care treatment.
Tumor resection is often followed by adjuvant therapy in some stage IB to IIIA patients where there is a risk of local failure and disease recurrence. This can be the case with close margins in proximity to vascular structures, tumor invasion of the chest wall, or lymph node involvement that is difficult to completely remove. Current adjuvant therapies (chemotherapy and/or in combination with radiotherapy or immunotherapy) involve multiple side effects, acquired resistance and limited tolerance in many patients.
Lumeda’s DigiLum™ presents a novel therapeutic paradigm in adjuvant therapy post-resection in applying a local therapy to the regional lymph node basin that is delivered with minimal morbidity immediately following resection of a primary tumor and its draining lymph nodes. Adjuvant PDT applied intraoperatively in this setting could dramatically reduce risk of disease recurrence and extend progression-free and long-term survival without the side effects of other adjuvant therapies.
COMBINATION PDT + IMMUNOTHERAPY
Many consider that the paramount achievement in cancer treatment in the last decade has been the introduction of immune checkpoint inhibitors (ICIs). ICIs are antibody-based agents that mobilize the immune T cell response. Despite the promise of immunotherapy, only 15-20% of patients benefit from it, with about half of lung cancer patients developing resistance to immunotherapy because they have so-called “cold” tumors that have not provoked a strong immune response. T cells are unable to penetrate such tumors being excluded by components of the cell microenvironment that stifle the normal immune response. ICIs work best in so-called “hot” tumors that have been infiltrated by T cells, creating an inflamed tumor. With T cells present within the tumor, they are mobilized against the cancer when ICIs trigger their release.
There is significant interest in developing treatment strategies that involve converting cold tumors to hot tumors by combining therapies that enhance anti-tumor T cell activity with ICIs. PDT provokes a strong acute inflammatory reaction observed as localized edema at the targeted site- a result of PDT-induced oxidative stress which can activate an immune response against tumor cells. PDT-induced immunomodulation of the tumor microenvironment and its ability to reset checkpoint homeostasis has been validated in numerous pre-clinical studies on animal models. These studies show that cancer tumors treated with PDT can stimulate the host anti-tumor response and alter the immune contexture to overcome tumor immunosuppressive activity and potentially increase patient response to ICIs. Other studies show that PDT dosing can be modulated to promote these effects.
Lumeda’s DigiLum™ is an ideal platform to offer a level of control required to optimally stimulate these effects. Currently cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1 (PD-1) are indicated for use in treating NSCLC based on stage, disease progression, and genomic test screening. The Lumeda solution has the potential to be among the first used in clinical studies to evaluate safety and effectiveness of PDT plus PD-1 immune checkpoint inhibitors as a synergistic anti-tumor therapy in treating NSCLC with pleural disease.