Emavusertib (CA-4948) in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer

NCT07107750 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202512063
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Metastatic Biliary Tract Carcinoma; Metastatic Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• To determine the safety of emavusertib in combination with gemcitabine, cisplatin, and durvalumab in patients with BTC as measured by incidences and types of adverse events

  Graded using CTCAE version 5.0.

  From consent through 30 days after last dose of study treatment (estimated to be 15 months)

• Dose escalation only: To determine an expansion dose for emavusertib in combination with gemcitabine, cisplatin, and durvalumab in patients with BTC.

  Completion of cycle 1 (each cycle is 21 days)

Secondary Outcomes (5)

• Progression-free rate (PFR)

  At 6 months from start of treatment

• Disease control rate (DCR)

  At 6 months from start of treatment

• Overall response rate (ORR)

  Through completion of treatment (estimated to be 14 months)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 38 months)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 38 months)

Study Arms (3)

Dose Escalation Dose Level 0 (starting dose): Emavusertib + Gemcitabine + Cisplatin + Durvalumab

EXPERIMENTAL

* Treatment will be administered on a 21-day cycle. * Emavusertib will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with emavusertib as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9).

Dose Escalation Dose Level -1: Emavusertib + Gemcitabine + Cisplatin + Durvalumab

EXPERIMENTAL

* Treatment will be administered on a 21-day cycle. * Emavusertib will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with emavusertib as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9).

Dose Expansion: Emavusertib + Gemcitabine + Cisplatin + Durvalumab

EXPERIMENTAL

* Treatment will be administered on a 21-day cycle. * Emavusertib will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with emavusertib as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9).

Interventions

Emavusertib DRUG

Provided by Curis.

Also known as: CA-4948

Gemcitabine DRUG

Standard of care.

Also known as: Gemzar

Cisplatin DRUG

Standard of care.

Also known as: Platinol

Durvalumab BIOLOGICAL

Standard of care.

Also known as: Imfinzi

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• No prior systemic treatment for advanced unresectable or metastatic BTC with the following exceptions:
• 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.
• ECOG performance status 0, 1, or 2
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x IULN or ≤ 3 x IULN in patients with documented Gilbert's syndrome
• AST(SGOT)/ALT(SGPT) ≤ 2 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN
• Creatinine clearance ≥ 35 mL/min by Cockcroft-Gault
• INR ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤1.5 x IULN

You may not qualify if:

• Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment. Use of medical marijuana is permitted.
• A history of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease; 2) or known indolent malignancies that do not require treatment and will likely not alter the course of treatment of BTC in the opinion of the investigator
• History of allogeneic organ or stem cell transplant.
• Currently receiving any other investigational therapeutic agents. Investigational tracers related to imaging studies are allowed with a 7 day-washout.
• Clinically active CNS metastasis; treated and asymptomatic metastasis allowed at the discretion of the sponsor/investigator or site PI. Radiotherapy to the brain must be completed \> 10 days prior to planned C1D1.
• Chemoradiation with curative intent within 6 months prior to C1D1 of study therapy.
• Palliative radiation therapy within 10 days prior to C1D1 of study therapy.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to emavusertib, gemcitabine, cisplatin, durvalumab, or other agents used in the study.
• Concomitant use of drugs with a known risk of causing prolonged QTc (with exception of Zofran if needed for supportive care) and/or Torsades de Pointes or a history of risk factors for Torsades de Pointes.
• Presence of interstitial lung disease or pneumonitis ≥ G2 at time of screening.
• Administration of a live attenuated vaccine within 30 days prior to C1D1
• QTc (Fridericia) \>470ms on screening EKG.
• Gastrointestinal condition which could impair absorption of emavusertib or inability to ingest emavusertib in the opinion of the investigator.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia in the opinion of the investigator.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of C1D1.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Curis, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

CA-4948; Gemcitabine; Cisplatin; durvalumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Olivia Aranha, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivia Aranha, M.D., Ph.D.

CONTACT

314-747-7509; oaranha@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 6, 2025
• Study Start: March 31, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): May 31, 2032
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)