TT-00420 Monotherapy in Refractory Cholangiocarcinoma: Phase 1 Results

At the ESMO 23rd World Congress on Gastrointestinal Cancer (ESMO GI 2021), Dr. S. Piha-Paul and colleagues from MD Anderson Cancer Center presented the results of a Phase 1 clinical trial evaluating the novel multikinase inhibitor TT-00420.

Study Design: TT-00420 Phase 1 Trial

The study evaluated TT-00420 as a monotherapy in patients with advanced refractory solid tumors, including a specific cohort of patients with cholangiocarcinoma (bile duct cancer).

• Cholangiocarcinoma Cohort (N=9):
  • Median of 3 prior lines of therapy.
  • 88.9% had intrahepatic cholangiocarcinoma.
  • 77.8% (N=7) were positive for FGFR2 fusions or rearrangements.

Patients received oral TT-00420 at doses ranging from 1 mg to 5 mg in 28-day cycles.

Key Efficacy Results

In the subset of patients with FGFR2-positive cholangiocarcinoma (N=5 evaluable):

• Partial Response (PR): 2 patients.
• Stable Disease (SD): Observed in several patients, with one patient continuing treatment for 9 months before undergoing surgical resection.
• Overall, antitumor activity was observed across all evaluable patients in this cohort.

Safety Profile

The most common adverse events (incidence >20%) included:

• Hypertension
• Diarrhea and Vomiting
• Hand-Foot Syndrome
• Nausea

These side effects were generally manageable through dose reductions or standard supportive care.

Conclusion

The researchers concluded that TT-00420 monotherapy shows encouraging preliminary efficacy in patients with heavily pretreated, FGFR2-positive advanced cholangiocarcinoma. These findings support further clinical investigation to determine the drug's role in the evolving treatment landscape for bile duct cancers.

Source: Annals of Oncology - TT-00420 Phase 1 Results

#BiliaryTractCancer #Cholangiocarcinoma #TT00420 #FGFR2 #MultikinaseInhibitor #CancerResearch #ESMOGI2021

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