Immunotherapy is a promising and evolving treatment for cancer that harness the body’s own immune system to target and kill cancer cells. However, not everyone responds to treatment and some immunotherapies are associated with severe side effects.
JK08 is an immunocytokine fusion protein designed to synergistically widen the therapeutic windows of validated cancer targets CTLA-4 and IL-15.
JK08 Design and Rationale
Positive Initial Data from Phase 1b/2 Clinical Trial of JK08 in Solid Tumors
Initial data from the first-in-human study evaluating JK08 included safety data from 32 patients with relapsed or refractory solid tumors who received subcutaneous JK08 monotherapy once weekly. JK08 was well tolerated, demonstrating preliminary disease stability and anticipated modulation of target immune cell populations in heavily pre-treated patients. Marked induction of NK and CD8+ T cells was observed, and corresponding activation of these cell populations was demonstrated through increased HLA-DR expression within these populations. More than 20% of heavily, pre-treated advanced metastatic cancer patients have remained on treatment for 3 months or longer, demonstrating preliminary clinical benefit with monotherapy JK08.
The most common adverse events were mild to moderate (Grade 1 & 2) and consisted of injection site reactions (ISRs), fatigue, pyrexia, anemia and nausea. No dose limiting toxicities or drug related adverse events leading to treatment discontinuations have been observed to date.
JK08 builds upon a breadth of clinical studies with CTLA-4 antibodies and recombinant IL-15 molecules demonstrating the therapeutic potential of each molecule individually. The CTLA-4-specific antibody ipilimumab validated CTLA-4 as a target for cancer therapy, but response rates are limited. Clinical sample analysis demonstrated that NK cells are important for ipilimumab responses. Recombinant IL-15 has exhibited potent stimulation of NK cell expansion and activation in pre-clinical and clinical studies. Through the incorporation of a CTLA-4 antibody and IL-15 into a single molecule, JK08 can channel the potent immune stimulation of IL-15 through the CTLA-4 antibody domain towards depletion of T-regulatory cells and targeted reversal of immunosuppression which may contribute to cancer progression.
JK08 is being evaluated in a Phase 1b/2 trial in solid tumors and is actively recruiting patients.