Phase 2 Study of CTX-009 plus Paclitaxel in Patients with Advanced BTC

March 2023, Vol 4, No 1

Do-Youn Oh, MD, PhD

Many novel treatment options are being investigated in patients with advanced biliary tract cancer (BTC), including CTX-009, a bispecific antibody that simultaneously inhibits delta-like ligand 4/Notch-1 and VEGF, which play an important role in angiogenesis. Results from a phase 1b trial of CTX-009 in combination with paclitaxel in patients with BTC were encouraging, including durable partial responses (PRs) in 2 of 3 patients. Dr Do-Youn Oh 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. In all, 11 patients were treated in the second line, whereas 13 patients were treated in the third line. Of these, 9 patients had intrahepatic cholangiocarcinoma (iCCA), 3 had extrahepatic CCA (eCCA), 7 had gallbladder cancer, and 5 had ampullary carcinoma.


Dr Do-Youn Oh 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.

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 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 ≥1 any-grade 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%).

Overall, CTX-009 plus paclitaxel showed promising efficacy in patients with advanced BTC treated in the second- or third-line setting. This study warrants future investigation into the potential safety and efficacy of this regimen.

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.

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