Celldex presents data from oncology portfolio

Celldex Therapeutics announced data from multiple presentations at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020). An interim update from the Company's ongoing Phase 1 study of its CD40 agonist antibody, CDX-1140, and preclinical data from its AXL discovery program were presented at the meeting. In addition, the Phase 1 study design for the Company's bispecific candidate, CDX-527, which couples CD27 co-stimulation with blockade of the PD-L1/PD-1 pathway, were also presented in a clinical trial in progress poster. Presentation Highlights CDX-1140 Presentation Highlights (Poster #405): CD40, expressed on dendritic cells and other antigen presenting cells, is an important target for immunotherapy, as it plays a critical role in the activation of innate and adaptive immune responses. CDX-1140 is a fully human agonist anti-CD40 monoclonal antibody that was specifically designed to balance good systemic exposure and safety with potent biological activity, a profile which differentiates CDX-1140 from other CD40-activating antibodies. CDX-1140 is currently in a Phase 1 dose escalation and expansion study. The study includes monotherapy and combination cohorts, including with CDX-301, Celldex's dendritic cell growth factor, with the PD-1 inhibitor pembrolizumab in patients who have progressed on checkpoint therapy and in combination with standard of care chemotherapy (gemcitabine and nab-paclitaxel) in first line metastatic pancreatic cancer. Prior data presented at SITC 2019 established the maximum tolerated dose (MTD) and recommended dose for continued study at 1.5 mg/kg-one of the highest systemic dose levels in the CD40 agonist class. The update presented at SITC 2020 focused on patients treated at the MTD from both the monotherapy (n=25) and CDX-301 (n=16) combination cohorts. In addition, preliminary safety data from the combination cohort with pembrolizumab (n=9; 4 at 0.72 mg/kg and 5 at 1.5 mg/kg CDX-1140) were also presented. CDX-1140 monotherapy and in combination with CDX-301 or pembrolizumab was generally well tolerated with mostly grade 1 or grade 2 drug related adverse events. Clinical activity both as a monotherapy and in combination with CDX-301 has been previously reported for CDX-1140 at varying doses, including an unconfirmed partial response (uPR) and tumor cavitation. At SITC 2020, analysis was focused on patients treated at the MTD and recommended dose of 1.5 mg/kg. 41 patients had been treated at the 1.5 mg/kg dose at the time of data cutoff; 29 patients had post-treatment scans performed and five patients had not reached their first post-treatment response assessment. Activity at 1.5mg/kg dose of CDX-1140 to date included: An ongoing (6+ months) complete response (CR) in a patient with follicular lymphoma treated with CDX-1140 in combination with CDX-301; Notable tumor shrinkage and/or necrosis in 6 patients with squamous cell head and neck cancer (SCCHN), including extensive tumor cavitation/necrosis of a large baseline protruding neck mass associated with decreased tumor pain in a patient; and, Stable disease (n=10) for 11 to 32 weeks. CDX-1140 at the recommended dose of 1.5 mg/kg provided good systemic exposure that enhanced the distribution into tissues and tumor and resulted in marked changes in the tumor microenvironment (TME) consistent with a more inflammatory and less immunosuppressive state as demonstrated by gene expression analysis. Interferon signaling and cytotoxicity pathways were most highly upregulated, while immunosuppression via TGFb signaling and metastatic pathways were downregulated, marking the first clear demonstration in patients of biological activity within the TME for a systemically administered agonist anti-CD40 mAb. Pre-treatment of patients with CDX-301 greatly increased the number of circulating dendritic cells prior to CDX-1140 administration and peripheral blood mononuclear cells (PBMCs) isolated from CDX-301 pretreated patients were more responsive to CDX-1140 than PBMCs from non-pretreated patients. Ongoing cohorts: The combination of CDX-1140 with pembrolizumab has completed the safety run-in and expansion cohorts in patients with checkpoint-refractory squamous cell head and neck cancer and non-small cell lung cancer have initiated. The combination of CDX-1140 with gemcitabine/nab-paclitaxel recently opened to enrollment to patients with previously untreated metastatic pancreatic adenocarcinoma. Data updates from these cohorts are expected in the first half of 2021.