GDFATHER is an open-label, multicenter, Phase I clinical trial evaluating intravenous (IV) administration of CTL-002 as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor. The trial is recruiting patients with advanced-stage, solid tumors, who have relapsed or are refractory to previous anti-PD-1/PD-L1 treatments. The trial is designed with two stages: Part A being a dose escalation study to MTD of CTL-002 in combination with a checkpoint inhibitor and part B expansion cohorts of dedicated GDF-15-dependent tumor indications that are checkpoint inhibitor relapsed/refractory. The trial is approved by regulators in Spain, Switzerland and Germany and may enroll up to 149 patients into part A and B combined.

“Our research has shown GDF-15 to be a malicious, tumor-produced factor that blocks immune effector cells from entering the tumor, thus interfering with immune cell activation and the killing of tumor cells. Blocking GDF-15 with CTL-002 should make modern immunotherapies more effective and potentially provide a major leap forward for the group of GDF-15-mediated checkpoint-inhibitor relapsed/refractory patients,” said Prof. Dr. Eugen Leo, Chief Medical Officer of CatalYm. “Moreover, we are delighted that regulators appreciated our efficient and tailored trial design that includes the immediate combination of CTL-002 with a checkpoint inhibitor allowing participating patients access to a promising, attractive antibody combination therapy from the very start of this clinical trial.”

Dr. Manfred Rüdiger, CEO of CatalYm, concluded: “We are proud of having achieved this important milestone, during this challenging time, that has involved great contributions from our team and our advisors. We look forward to delivering potentially better treatment options for patients failing on current checkpoint blocker treatment regimes.”

CTL-002
CTL-002 is a humanized, monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15). High concentrations of GDF-15 in the serum and tumor-microenvironment help the tumor evade the immune system and are associated with resistance to current therapies.* CTL-002 addresses three of the tumor’s immune suppressive mechanisms all involving the inhibitory effect of GDF-15 on the immunostimulatory LFA-1/ICAM-1 interaction. By neutralizing GDF-15, CTL-002 is expected to enhance infiltration of immune cells into the tumor, improve priming of T cells by dendritic cells and improve tumor killing by T cells and NK cells.

About Concept of the clinical trail
The GDFATHER trial (GDF-15 Antibody-mediaTed Effector cell Relocation) is a Phase I, first-in-human, multicenter, two-part (part A: dose escalation and part B: cohort expansion) clinical trial of intravenous (IV) administration of CTL-002 as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients with advanced-stage, relapsed/refractory solid tumors, that relapsed post or were refractory to a prior anti-PD-1/PD-L1 therapy. The primary objectives of the study are to characterize the safety and tolerability of CTL-002 and to explore the preliminary anti-tumor activity of CTL-002 in the expansion cohorts. More information on trial can be found at https://clinicaltrials.gov.

CatalYm is a biopharmaceutical company developing novel cancer immunotherapies targeting Growth-and-Differentiation Factor 15 (GDF-15). Apart from its established role in cachexia, GDF-15 has been associated with immunosuppression in tissues and tumors and a rapidly growing body of literature supports the concept that GDF-15 is a major T cell repellent. CatalYm aims to neutralize GDF-15 to turn “cold” tumors “hot” and thereby substantially improving the efficacy of established immunotherapy such as anti-PD1/-PD-L1 checkpoint inhibitors. The company’s lead product candidate CTL-002, a neutralizing GDF-15 antibody, is currently under clinical evaluation in a two-part, open-label, multicenter, Phase I clinical trial (GDFATHER trial).

References: * Front. Immunol. 11:951. doi: 10.3389/fimmu.2020.00951