On October 8, 2021 Compass Therapeutics, Inc. (OTC:CMPX) and ABL Bio (KOSDAQ: 298380) reported that 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 (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Abstract Number: 4749; Session Title: Plenary Session 2: New Drugs on the Horizon I) (Press release, Compass Therapeutics, OCT 8, 2021, View Source [SID1234591025]).
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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 (DCR) 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).
"This is a significant clinical result because current approved anti-angiogenic drugs have little efficacy as a monotherapy. Furthermore, 94% of the colorectal patients and 58% of the gastric patients in this study were previously treated with Avastin (bevacizumab) or Cyramza (ramucirumab), respectively; the response rate is almost three times that seen for current 3rd and 4th line therapies in patients with colorectal and gastric cancers." said Jeeyun Lee, MD, a Professor at the Samsung Medical Center, Seoul, South Korea and the principal investigator of the study.
"The responses to CTX-009 as a monotherapy in this refractory patient population combined with the excellent tolerability profile suggests that CTX-009 can become an important drug for a broad range of solid tumors" said Thomas Schuetz, MD, PhD, CEO and scientific Founder of Compass Therapeutics. "We look forward to developing CTX-009 in the United States and other geographies and to unlocking its full potential". Compass Therapeutics of Boston, Massachusetts holds the global rights to CTX-009 with the exception of S. Korea (rights held by Handok) and China (rights were out-licensed to Elpiscience Biopharma).
"We are pleased to present the clinical data of CTX-009 (ABL001) for the first time at a prominent international conference," said Sang Hoon Lee, PhD, CEO of ABL Bio. "CTX-009 has demonstrated its potential to benefit cancer patients, especially those that have been unable to experience improvements with standard treatments. We expect to further validate the therapeutic value of CTX-009 as it progresses through clinical trials in the U.S., China and South Korea."
"We are happy to see the next frontier of anti-angiogenic therapies, CTX-009 (ES104) showing promising anti-tumor activity in a Phase 1 study as monotherapy," said Steve Chin, MD, CMO of Elpiscience Biopharma, "We look forward to initiating the clinical trials in China to explore its therapeutic potential in the heavily pre-treated digestive tract cancer patients."
About CTX-009
CTX-009 (ABL001/ES104) is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) 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.