ABC-08 Clinical Study

Phase Ib combination Acelarin + cisplatin in patients with locally advanced or metastatic biliary tract cancer

  • Locally advanced or metastatic biliary tract cancer
  • Front-line treatment
  • Combination Acelarin + cisplatin
  • Dose escalation: 3 + 3
    • Cohort 1: Acelarin 625 mg/m2 + cisplatin 25 mg/m2 (n=8)
    • Cohort 2: Acelarin 725 mg/m2 + cisplatin 25 mg/m2 (n=6)
  • Expansion Cohort at selected dose: Acelarin 625 mg/m2 + cisplatin 25 mg/m2 (n=6)
  • Primary Objective: Dose selection
ABC-08 study image of lady
Demographic Cohort 1 + Cohort 2
Patients 14
Evaulable Patients (≥1 cycle) 11
Age
(median)
61
(range 48-78)

Interim Results
(Cohort 1)

In January 2018, NuCana announced interim results from the multi-center ABC-08 study. A complete response was achieved in one patient, partial responses in three patients, and stable disease in another patient, resulting in an objective response rate of 50% and a disease control rate of 63% on an intent-to-treat basis. This is an improved response rate compared to that seen with the current standard treatment for inoperable biliary tract cancer. The combination of Acelarin and cisplatin was well-tolerated with no unexpected adverse events and no dose-limiting toxicities. The optimal dose combination was determined to be Acelarin at 625 mg/m2 with cisplatin at 25 mg/m2.

(Cohort 2)

In October 2018, NuCana announced additional interim results from this study. Acelarin combined with cisplatin was observed to continue to achieve approximately a doubling of the response rate expected with the standard of care, gemcitabine plus cisplatin. In addition, results showed the combination was well-tolerated and several patients achieved significant reductions in their tumour volume as well as further tumour shrinkage over time. Fourteen patients with advanced/metastatic biliary tract cancer received Acelarin (625 mg/m2 or 725 mg/m2) and cisplatin (25 mg/m2) on days one and eight of a three-week cycle. In the intent-to-treat group of patients, a Complete Radiological Response was achieved in one patient and a Partial Response in six patients, resulting in an Objective Response Rate of 50%. In the eleven Efficacy Evaluable patients (defined as those patients who received at least one cycle of therapy), an Objective Response Rate of 64% was achieved.

Based on these encouraging interim results, we plan to initiate a Phase III study of Acelarin and cisplatin as a front-line treatment of patients with locally advanced or metastatic biliary tract cancers in 2018.

Comparison of the response rate data from the ABC-08 and ABC-02 studies

ABC-08 ABC-021
Acelarin + cisplatin
625 mg/m2 or 725 mg/m2
+ 25 mg/m2
gemcitabine + cisplatin
1000 mg/m2
+ 25 mg/m2
Complete Response 7% (1/14) 0.6% (1/161)
Partial Response 43% (6/14) 25.5% (41/161)
Objective Response Rate 50% (7/14) 26.1% (42/161)

1. Valle et al.N Engl J Med 2010 Apr 8;362(14):1273-81