On October 23, 2023 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported that positive initial data from the first-in-human study evaluating JK08 in adults with solid tumors were presented in a poster session during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2023 (Press release, Salubris Biotherapeutics, OCT 23, 2023, View Source [SID1234636283]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The presentation included safety data from 32 patients with relapsed or refractory solid tumors who received subcutaneous JK08 monotherapy once weekly in this Phase 1b/2 dose escalation study. At the dose levels evaluated to date, JK08 has been 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 has been observed, and corresponding activation of these cell populations has been 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, with the longest continuing therapy for 29 weeks. The most common adverse events have been mild to moderate (Grade 1 & 2) and consist 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 combines CTLA-4 targeting with the effects of IL-15, with the aim of enhancing anti-tumor immune responses while managing potential side effects," said Sam Murphy, Chief Executive Officer of SalubrisBio. "We are pleased to see promising, dose-dependent pharmacodynamic activity and a favorable safety and tolerability profile in this heavily pre-treated patient population. While early, the data are very encouraging and we look forward to further evaluating JK08’s potential for solid tumor patients."
The ongoing Phase 1b/2, open label, dose escalation and cohort expansion study (NCT05620134) is designed to evaluate the safety and preliminary anti-tumor activity of JK08 in patients with unresectable locally, advanced or metastatic cancer. After dose escalation, monotherapy and combination dose expansion cohorts are planned. SalubrisBio plans to report additional data from this study at future medical meetings.
About JK08
JK08 is a recombinant fusion protein consisting of a CTLA-4-specific antibody and an IL-15 fusion domain. The JK08 design builds upon a breadth of clinical studies with CTLA-4 antibodies and recombinant IL-15 molecules, which together portend synergistic effects in an antibody fusion construct. The CTLA-4-specific antibody ipilimumab validated CTLA-4 as a target for cancer therapy, but response rates are limited. Analysis of clinical samples demonstrated that NK cell activity signatures and ADCC biomarkers correlate with ipilimumab responses. Recombinant IL-15 has exhibited potent stimulation of NK cell expansion and enhancement of ADCC 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.