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Metastatic Biliary Tract CancerPhase 1NCT07107750

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

A Phase 1 study testing Emavusertib, Gemcitabine and Cisplatin in people with Metastatic Biliary Tract Cancer and Metastatic Biliary Tract Carcinoma, run by Washington University School of Medicine at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Emavusertib, Gemcitabine and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
27 Mar 2026to 31 May 2032
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Creatinine phosphokinase (CPK) elevation at screening < Grade 2 (CPK < 2.5 x IULN).
  • Patients on a cholesterol lowering statin must be on a stable dose with no dose changes within 3 weeks prior to study start.
  • The effects of emavusertib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 90 days after completion of the study.
  • Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Who cannot join

  • 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.
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  • 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.
  • Patients with known HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines and in line with contraindicated concomitant medications is recommended.
  • Participants with active, known, or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussion with the sponsor-investigator or site PI.
  • Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study treatment except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted. Inhaled intranasal, intra-articular, and topical steroid uses are permitted.
  • History of grade 3 or greater rhabdomyolysis that did not completely resolve.
  • Patients are unwilling to adhere to the lifestyle guidance

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

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

314-747-7509

oaranha@wustl.edu

United States1 site, 1 recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Olivia Aranha, M.D., Ph.D., 314-747-7509, oaranha@wustl.edu

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

    Recruiting

Other trials in United States

About this study

Official title: Phase I Trial of Emavusertib (CA-4948) in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer

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).

Read the detailed description

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.

Being tested
Emavusertib, Gemcitabine, Cisplatin, Durvalumab
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EmavusertibDrug

    Also called CA-4948

    Provided by Curis.

  • GemcitabineDrug

    Also called Gemzar

    Standard of care.

  • CisplatinDrug

    Also called Platinol

    Standard of care.

  • DurvalumabBiological

    Also called Imfinzi

    Standard of care.

Study groups in NCT07107750
Study groupRoleWhat they receive
Dose Escalation Dose Level 0 (starting dose): Emavusertib + Gemcitabine + Cisplatin + DurvalumabExperimental* 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 + DurvalumabExperimental* 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 + DurvalumabExperimental* 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).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

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

    Measured: Completion of cycle 1 (each cycle is 21 days)

Secondary outcomes (5)

  1. Progression-free rate (PFR)

    • Defined as the proportion of evaluable patients who are free of disease progression/recurrence at 6 months from the start of treatment.
    • Response and progression will be evaluated in this study using the revised international criteria (RECIST version 1.1) proposed by the RECIST committee as well as the modified iRECIST guidelines. Until radiographic progression based on RECIST 1.1, there is no distinct iRECIST assessment.

    Measured: At 6 months from start of treatment

  2. Disease control rate (DCR)

    • DCR is the proportion of patients with either complete response (CR), partial response (PR), or stable disease (SD) (with a duration of SD for 6 months).
    • Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: At 6 months from start of treatment

  3. Overall response rate (ORR)

    • ORR = number of patients with complete response or partial response
    • Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Through completion of treatment (estimated to be 14 months)

  4. Progression-free survival (PFS)

    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. The alive patients without progression are censored at the last follow-up.
    • Response and progression will be evaluated in this study using the revised international criteria (RECIST version 1.1) proposed by the RECIST committee as well as the modified iRECIST guidelines. Until radiographic progression based on RECIST 1.1, there is no distinct iRECIST assessment.

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

  5. Overall survival (OS)

    OS is defined as the duration of time from start of treatment to time of death from any cause. The alive patients are censored at the last follow-up.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2025
  2. Study start27 Mar 2026
  3. Primary completion30 Jun 2030 (estimated)
  4. Study completion31 May 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07107750
Sponsor's protocol ID
202512063
Status last verified
Mar 2026
First submitted
30 Jul 2025
Last updated
3 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Emavusertib, Gemcitabine and Cisplatin in people with Metastatic Biliary Tract Cancer and Metastatic Biliary Tract Carcinoma, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Olivia Aranha, M.D., Ph.D. (314-747-7509, oaranha@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: From consent through 30 days after last dose of study treatment (estimated to be 15 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07107750.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2026.

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