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CholangiocarcinomaPhase 1/2NCT05874414

Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutated Cholangiocarcinoma

A Phase 1/2 study testing GNS561 + Trametinib in people with Cholangiocarcinoma, run by Genfit at 11 sites in 2 countries.

Recruiting

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

Sites and contacts
Official record
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Trial summary

This is an open-label, multicenter Phase 1b/2a study to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of GNS561 in combination with trametinib in Advanced KRAS Mutated Cholangiocarcinoma after failure of standard-of-care first line therapy Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma
What is being tested?
GNS561 + Trametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
11 sitesin 2 countries
Study dates
21 Aug 2023to Jun 2028
Phase
Phase 1/2
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

  • Histologically confirmed intrahepatic CCA with a documented KRAS mutation.
  • Patients greater than or equal to 18 years of age.
  • Patients must have disease progression that is not amenable to potentially curative treatment.
  • Patients must have received one or two lines of chemotherapy.
  • Patients must have at least one measurable disease by RECIST v1.1.
  • Performance status (ECOG) 0-1.
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  • Adequate organ baseline function defined as follows: absolute neutrophil count ≥1000 cells/μL, platelet count ≥75,000 cells/μL, hemoglobin ≥9 g/dL, aspartate aminotransferase or alanine aminotransferase less than or equal to 3 × upper limit of normal, estimated glomerular filtration rate ≥60 mL/min, corrected QT interval by Fridericia's (QTcF) interval ≤470 msec.
  • Women of childbearing potential must present with a negative serum pregnancy test and agree to use adequate contraception during the study and until 6 months after the end of treatment. Male patients with women partners of childbearing potential must agree with the contraception procedures of the study protocol.
  • Patients must be able to understand and be willing to comply with the requirements of the study protocol.
  • Patients participate voluntarily and sign informed consent form(s).

Who cannot join

  • Previous treatment with a MEK inhibitor or autophagy inhibitor.
  • Previous treatment with three or more lines of prior chemotherapy.
  • Extrahepatic CCA with recent (within 6 weeks) placement of a stent or episodes of unstable biliary stents (manifest as obstruction, migration of the stent, infevtion or mechanical failure of the stent) within 6 weeks according to investigator's judgement.
  • Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders: congestive heart failure New York Heart Association ≥ class 2 or left ventricular ejection fraction (LVEF) <50%, arrythmias or cardiac conduction abnormalities. Uncontrolled arterial hypertension or inadequately controlled arterial hypertension, at the discretion of the investigator, based on an average of = >3 BP readings over = >2 sessions.
  • Patients who have retinal condition (retinal tear, exudate, hemorrhage) or history of retinal vein occlusion or central serous retinopathy or retinal pigment epithelial detachment.
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  • History of interstitial lung disease or pneumonitis.
  • Patients who have clinically significant pleural effusion or ascites.
  • Patients who have neurological condition (e.g., tremor, ataxia, hypotension, confusion), history of seizures or active central nervous system metastases.
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., diarrhea, active ulcer disease, history of gastrointestinal perforation/hemorrhage, malabsorption or other conditions that under the judgment of the principal investigator (PI) may impair absorption of study drugs).
  • Patients who are taking antineoplastic drugs for concomitant cancer or history of malignancy other than CCA within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%) such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
  • Any other condition that would, in the Investigator s judgment, contraindicate the patients' participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection, unable to swallow medication, social/psychological issues, etc).
  • Known active viral hepatitis, including HBV and HCV.
  • Patients with known allergic reaction to quinoline derivatives (e.g., quinine, chloroquine, mefloquine) and/or hypersensitivity to study drugs.
  • Patients who have not recovered for certain AEs due to previous lines of therpay.
  • Female patients who are pregnant or lactating at the time of enrollment.

Trial locations and contacts

11 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Pejvack MOTLAGH, CMO contact

+33320164092

contact@genfit.com

Pejvack MOTLAGH, CMO contact

+33320164092

pejvack.motlagh@genfit.com

11 sites in 2 countries

United States10 sites, 8 recruiting

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

    Terminated

  • University of Virginia Comprehensive Cancer Center

    Charlottesville, Virginia, 22908

    University of Virginia Health System

    Recruiting

  • University Of Chicago Medical Center

    Chicago, Illinois, 60637

    University Of Chicago Medical Center

    Recruiting

  • University of Texas, MD Anderson Cancer Center

    Houston, Texas, 77030

    The University of Texas, MD Anderson Cancer Center

    Recruiting

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

    USC Norris Comprehensive Cancer Center

    Recruiting

  • LACN Aneheim Flagship Office

    Los Angeles, California, 92805

    LACN Aneheim Flagship Office

    Recruiting

  • Froedtert Hospital and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Medical College of Wisconsin

    Recruiting

  • Orlando Health

    Orlando, Florida, 32806

    Orlando Health

    Recruiting

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Terminated

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Moffitt Cancer Center

    Recruiting

Other trials in United States

Puerto Rico1 site, 1 recruiting

  • Pan American Center for Oncology Trials, LLC

    Rio Piedras, Puerto Rico, 00935

    Pan American Center for Oncology Trials, LLC

    Recruiting

Other trials in Puerto Rico

About this study

Official title: Phase 1b/2a Study of GNS561 in Combination With Trametinib in Advanced KRAS Mutated Cholangiocarcinoma

This is an open-label, multicenter Phase 1b/2a study to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of GNS561 in combination with trametinib in Advanced KRAS Mutated Cholangiocarcinoma after failure of standard-of-care first line therapy

Being tested
GNS561 + Trametinib
Keywords
GNS561, Cholangiocarcinoma, Trametinib, Phase1b/2a, Bile Duct cancer
Medical subject headings
Cholangiocarcinoma, Bile Duct Neoplasms

What participants receive

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

  • GNS561 + TrametinibDrug

    Also called Ezurpimtrostat (GNS561)

    GNS561: 50mg, 100mg, 150mg, 200mg and trametinib: 1mg, 1.5mg and 2mg

Study groups in NCT05874414
Study groupRoleWhat they receive
GNS561+TrametinibExperimentalPhase 1b Dose Finding Patients will receive GNS561 (50mg QD; 100mg QD; 150mg; 200mg QD) and trametinib (2mg QD; 1.5mg QD; 1mg QD) in a dose escalation/de-escalation design to determine the maximum tolerated dose (MTD) of the combination. Experimental: Phase 2a Patients will receive GNS561 and trametinib at the recommended dose of the combination determined during Phase 1b
Receives: Drug: GNS561 + Trametinib

What is being measured

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

  1. Incidence of dose limiting toxicity (DLT) of GNS561 with trametinib (Phase 1b)

    Defined as Treatment Emergent Adverse Event (TEAE) being at least possibly related to study drug: With Grade ≥ 3 (using NCI CTCAE Version 5.0 or higher as applicable) such as specified in the protocol

    Measured: At the end of Cycle 1 (each Cycle is 21 days)

  2. Objective response rate (ORR) of the combination of GNS561 with trametinib (Phase 2a)

    Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

    Measured: Up to 11 months (estimated)

Secondary outcomes (9)

  1. Duration of response (DoR)

    Defined as the duration between first documentation of CR or PR to first documentation of disease progression or death using RECIST v1.1

    Measured: Up to 11 months (estimated)

  2. Progression-free survival (PFS)

    Defined as the time from the date of first dose of study drug to the date of first documented disease progression or death

    Measured: Up to 11 months (estimated)

  3. Time To Progression (TTP)

    Defined as the time from first dose of study drug to the date of first documented disease progression.

    Measured: Up to 11 months (estimated)

  4. Disease Control Rate (DCR)

    defined as the proportion of patients with a best overall response of CR or PR or stable disease (SD) using RECIST v1.1

    Measured: Up to 11 months (estimated)

  5. Time To Response (TTR)

    Defined as the time from first dose of study drug to first documentation of CR or PR using RECIST v1.1

    Measured: Up to 11 months (estimated)

  6. Overall Survival (OS) time

    Defined as the time from the date of first dose of study drug to the date of death due to any cause.

    Measured: Up to approximately 42 months

  7. Incidence and severity of treatment emergent adverse event (TEAEs), incidence of serious adverse events (SAEs), incidence of TRAEs, incidence of adverse events of special interest (AESIs), rate of treatment discontinuation or interruption for TRAEs

    graded according to NCI CTCAE v5.0

    Measured: Up to 11 months (estimated)

  8. Incidence of clinically significant changes or abnormalities from physical examinations, ophthalmologic assessments, vital signs, performance scores, laboratory results, ECGs, echocardiograms or multigated acquisition scans

    Measured: Up to 11 months (estimated)

  9. Drug concentration in plasma for GNS561 and trametinib

    Measured: Predose to Day 21 of Cycle 1 and predose to Day 21 of Cycle 2 (each Cycle is 21 days)

Timeline

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

  1. First posted24 May 2023
  2. Study start21 Aug 2023
  3. Primary completionDec 2027 (estimated)
  4. Study completionJun 2028 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
98 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05874414
Sponsor's protocol ID
GNS561-222-1
Status last verified
May 2026
First submitted
27 Apr 2023
Last updated
13 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GNS561 + Trametinib in people with Cholangiocarcinoma, run by Genfit at 11 sites in 2 countries.

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 10 inclusion and 16 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 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Puerto Rico. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Pejvack MOTLAGH, CMO (+33320164092, contact@genfit.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicity (DLT) of GNS561 with trametinib (Phase 1b) (time frame: At the end of Cycle 1 (each Cycle is 21 days)). 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 NCT05874414.

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 13 Jul 2026.

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