Intratumoral therapies is another class of immunotherapeutics that I often consider especially for folks with limited skin or nodal disease or perhaps deeper oligometastatic disease. I have cutaneous malignancies patients with Melanoma, Cutaneous SCC, Merkel cell and Kaposi sarcomas that have responded to local intratumoral therapies. We’ve seen viral agents like FDA approved TVEC, RP1, modified Polio under clinical trial or non-viral agents like plasmid IL-12, TLR-9 agonist under clinical trial respond with durability and presented at major conferences. Even patients who have had prior immunotherapy and were considered refractory to PD1 inhibitors.
Karin Donaldson is our senior research coordinator for the Solid Tumor Cellular Therapy/Phase 1 clinical trial sections and she shares details of a new protocol we have just opened. We are the first site in the country to now be site activated for this protocol and this includes ANY solid tumor patient with an accessible lesion to be considered if progressive disease beyond standard of care. Further details of the study can be found here. Enjoy! Dr Sajeve Thomas
Intratumoral (IT) therapy has become a growing interest in recent years and has become an important treatment option in the fight against cancer, particularly in cases where localized delivery of treatment is more advantageous than systemic therapy. In specific situations, IT injections can be a preferable choice compared to alternative treatments, particularly for patients with localized disease and tumors that are easily accessible via a needle or catheter.
Why choose an Intratumoral therapy?
- 1. Immune Stimulation: Intratumoral injections can help activate an immune response against the cancer cells. This is especially relevant in turning “cold” tumors into “hot” ones by promoting immune cell infiltration and activity in the tumor microenvironment.
- 2. Minimizing Systemic Side Effects: Targeted Intratumoral treatment can reduce the risk of systemic side effects associated with some cancer therapies. This is important for maintaining the patient’s overall well-being during treatment.
- 3. Maximizing Efficacy: Some treatments, particularly certain immunotherapies or targeted therapies, work more effectively when applied directly within the tumor microenvironment. Intratumoral delivery can maximize the concentration of the therapeutic agent at the tumor site, potentially enhancing its efficacy.
- 4. Targeted Delivery: Intratumoral therapy allows for highly localized and targeted treatment. By injecting drugs or therapeutic agents directly into the tumor, healthcare providers can deliver the treatment precisely where it is needed, minimizing exposure to healthy surrounding tissues.
What is CLN-617?
CLN-617 is a novel Intratumoral therapy that was discovered at Cullinan Oncology. Based on preclinical models, CLN-617 is a therapy that combines two potent antitumor cytokines—IL-2 and IL-12—into a single molecule. The molecule is designed for Intratumoral injection to enhance efficacy and reduce systemic toxicity. It employs collagen-binding and size-enhancing domains to retain the CLN-617 molecule inside the tumor tissue after Intratumoral injection to prevent leakage.
While CLN-617 stays inside the injected tumor, it directs a broad immune response, like a vaccine, that helps to eradicate not only the injected tumor, but also attack distant tumor sites as observed in preclinical studies. Local administration of CLN-617 promotes broad systemic immunosurveillance, potentially enabling the treatment of advanced disease, including mediating the regression of non-injected distal tumors and generating a memory of T cell responses to enhance long-term survival.
CLN-617 has the potential to be effective in several disease groups since collagen is expressed across all solid tumors. CLN-617 has the potential for efficacy as a monotherapy or in combination with checkpoint inhibitors. Preclinical studies show that CLN-617 can significantly impact the growth of non-injected tumors, and that combination with checkpoint inhibitors helps to completely eradicate distant tumors.
Cullinan Oncology has initiated a first-in-human Phase I clinical study designed to evaluate the safety and efficacy of CLN-617 alone and in combination with pembrolizumab in patients with ANY type of advanced solid tumors especially with limited disease to the skin, nodes and/or unresectable oligometastatic tumors. This study is being conducted at sites across the country, including the Orlando Health Cancer Institute.