Compass Therapeutics, Inc. and ABL Bio presented clinical trial data for CTX-009 (ABL001/ES104), a dual anti-angiogenic bispecific antibody targeting DLL4 and VEGF-A, at an oral plenary session during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Abstract Number: 4749; Session Title: Plenary Session 2: New Drugs on the Horizon I). The first in human Phase 1 single agent dose escalation and expansion study evaluated CTX-009 across nine dose levels. The study enrolled 45 heavily pre-treated patients with cancers primarily of colorectal and gastric origin.

CTX-009 was well tolerated across all doses evaluated, with no dose-limiting toxicities reported. The most frequent treatment related adverse event was hypertension, observed in 17 patients of the 45 patients enrolled. Among those, 7 patients reported Grade 3 hypertension and the rest had Grade 1 or Grade 2 (16%).

Only 4 mild cases of pulmonary hypertension were reported that were all reversible, and CTX-009 demonstrated significant clinical activity as a stand-alone therapy. The majority (87%) of the patients enrolled in the study had ECOG performance status of 1; 42% (n=19) were patients with gastric cancer and 40% (n=18) were patients with colorectal cancer with a median of three prior lines of systemic anticancer therapies. Importantly, 62% of the patients enrolled were previously treated with anti-VEGF antibodies containing regimens.

There were 4 partial responses (including three partial responses confirmed by RECIST 1.1 and one partial response which was unconfirmed) and 20 stable diseases among 39 evaluable patients. The confirmed overall response rate (ORR) across all dose levels tested (0.3 – 17.5mg/kg) was 8%, not including 1 unconfirmed partial response, and the disease control rate across all dose levels was 62%. The ORR at the recommended phase 2 doses (RP2D) of 10.0-12.5 mg/kg was 19% (n=3/16) not including one unconfirmed partial response, and the DCR at the RP2D was 69% (n=11/16).

CTX-009 (ABL001/ES104) is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Pre-clinical and early clinical data of CTX-009 suggests that blockade of both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic and non-small cell lung cancer. Partial responses to CTX-009 as a monotherapy have been observed in heavily pre-treated cancer patients, who were resistant to currently approved anti-VEGF therapies.

CTX-009 has completed a Phase 1 monotherapy dose escalation and expansion study. Phase 1b and Phase 2 combination studies are ongoing.