Patients With Advanced BTC Treated With CTX-009 Plus Paclitaxel in a Phase 2 Study

CTX-009 in combination with paclitaxel showed encouraging efficacy in patients with advanced biliary tract cancer.

CTX-009, a bispecific antibody that inhibits Delta-like ligand 4/Notch-1 as well as vascular endothelial growth factor, is currently being investigated to determine whether it can be efficacious in patients with advanced biliary tract cancer (BTC). A phase 1b trial of CTX-009 in combination with paclitaxel in patients with BTC showed encouraging results, including durable partial responses (PRs) in 2 of 3 patients. At ASCO Gastrointestinal Cancers Symposium 2023, Do-Youn Oh, MD, PhD, presented results from a phase 2 study of CTX-009 in combination with paclitaxel as second- or third-line therapy in patients with advanced BTC.

Do-Youn Oh, MD, PhD, presented results from a phase 2 study of CTX-009 in combination with paclitaxel as second- or third-line therapy in patients with advanced BTC.

As of November 2022, a total of 24 patients were enrolled, including 1 patient remaining on treatment. The primary end point was objective response rate (ORR), and secondary end points included time to treatment failure (TTF), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A total of 11 patients were treated in the second line, and 13 patients were treated in the third line. Of these patients, 9 had intrahepatic cholangiocarcinoma (iCCA), 3 had extrahepatic CCA, 7 had gallbladder cancer, and 5 had ampullary carcinoma.

After a median follow-up of 12.1 months, the ORR was 37.5% (95% confidence interval [CI], 18.8-59.4), with 9 confirmed PRs. Of the 9 patients with PRs, 3 had ampullary carcinoma, 3 had iCCA, 2 had gallbladder cancer, and 1 had eCCA. The ORR in patients treated in the second line was 63.6%, with 7 PRs, and the ORR was 15.4% in patients treated in the third line, with 2 PRs. The median PFS was 9.4 months (95% CI, 5.4-11.1), and the median OS was 12.5 months (95% CI, 10.9-not assessed [NA]). The OS rate at 12 months was 52.4% (95% CI, 30.7-70.2). The median DOR was 6.9 months (95% CI, 3.5-NA), and the median TTF was 5.9 months (95% CI, 3.9-9.8). All patients experienced grade ≥1 adverse event (AE), and 95.8% of patients experienced a grade ≥3 treatment-emergent AE (TEAE). Six patients discontinued treatment due to a TEAE. The most common grade ≥3 TEAEs were decreased neutrophil count (83.3%), anemia (20.8%), and hypertension (16.7%).

Patients with advanced BTC treated in the second- or third-line setting showed promising efficacy with CTX-009 plus paclitaxel. Future studies of this regimen’s safety and efficacy are warranted.

Source:

Oh DY, Park JO, Kim JW, et al. CTX-009 (ABL001), a bispecific antibody targeting DLL4 and VEGF A, in combination with paclitaxel in patients with advanced biliary tract cancer (BTC): a phase 2 study. Poster presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA. Abstract 540.