Emavusertib + Gemcitabine, Cisplatin and Durvalumab

The first part of the study will be dose escalation of emavusertib in combination with standard of care (SOC) cisplatin, gemcitabine, and durvalumab. Once the expansion dose of emavusertib is determined, the expansion part of the study will open. All patients will be treated with emavusertib in combination with SOC cisplatin, gemcitabine, and durvalumab for up to 8 total cycles. Patients may receive no more than 8 total cycles of gemcitabine and cisplatin for BTC.

Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore, some patients may only receive 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. After 8 cycles, patients will discontinue cisplatin and gemcitabine and continue maintenance emavusertib and durvalumab.

Based on preclinical data from the Lim lab (WUSM), the investigators hypothesize that IRAK4 inhibition cripples tumor-intrinsic survival signaling and effectively overcomes the desmoplastic and immune-suppressive tumor microenvironment (TME) to render chemo- and immunotherapies effective in GI malignancy.

Therefore, this trial is designed to evaluate the combination of emavusertib (CA-4948) and standard chemoimmunotherapy in untreated advanced or metastatic biliary tract cancer (BTC).

Live record on ClinicalTrials.gov →

• Advanced unresectable or metastatic histologically or cytologically confirmed adenocarcinoma of the biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma. Patients whose tumor have mixed histology but predominantly (>50%) adenocarcinoma are allowed.
• Measurable defined by RECIST v1.1.
• Neoadjuvant or adjuvant systemic therapy completed > 6 months from planned C1D1.
• Up to two prior cycles of gemcitabine/cisplatin/anti-PD1 with no evidence of disease progression is allowed
• At least 18 years of age.

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.