NCT05874414

Brief 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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
74

participants targeted

Target at P75+ for phase_1

Timeline
5mo left

Started Aug 2023

Typical duration for phase_1

Geographic Reach
2 countries

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress87%
Aug 2023Oct 2026

First Submitted

Initial submission to the registry

April 27, 2023

Completed
27 days until next milestone

First Posted

Study publicly available on registry

May 24, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

August 21, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2026

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2026

Expected
Last Updated

January 22, 2026

Status Verified

April 1, 2025

Enrollment Period

2.7 years

First QC Date

April 27, 2023

Last Update Submit

January 21, 2026

Conditions

Cholangiocarcinoma

Keywords

GNS561CholangiocarcinomaTrametinibPhase1b/2aBile Duct cancer

Outcome Measures

Primary Outcomes (2)

  • 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

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

  • 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)

    Up to 11 months (estimated)

Secondary Outcomes (9)

  • Duration of response (DoR)

    Up to 11 months (estimated)

  • Progression-free survival (PFS)

    Up to 11 months (estimated)

  • Time To Progression (TTP)

    Up to 11 months (estimated)

  • Disease Control Rate (DCR)

    Up to 11 months (estimated)

  • Time To Response (TTR)

    Up to 11 months (estimated)

  • +4 more secondary outcomes

Study Arms (1)

GNS561+Trametinib

EXPERIMENTAL

Phase 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

Drug: GNS561 + Trametinib

Interventions

GNS561 + TrametinibDRUG

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

Also known as: Ezurpimtrostat (GNS561)
GNS561+Trametinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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).

You may not qualify if:

  • Previous treatment with a MEK inhibitor or autophagy inhibitor.
  • Previous treatment with three or more lines of prior chemotherapy.
  • Extrahepatic CCA with
  • 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.
  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

LA Cancer Network

Los Angeles, California, 92801, United States

RECRUITING

Orlando Health

Orlando, Florida, 32806, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University Of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

TERMINATED

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

TERMINATED

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Pan American Center for Oncology Trials, LLC

Rio Piedras, Puerto Rico, 00935, Puerto Rico

RECRUITING

MeSH Terms

Conditions

CholangiocarcinomaBile Duct Neoplasms

Interventions

trametinib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsBiliary Tract NeoplasmsDigestive System NeoplasmsNeoplasms by SiteBile Duct DiseasesBiliary Tract DiseasesDigestive System Diseases

Study Officials

  • Peter Lichten, M.D.

    Genfit

    STUDY DIRECTOR

Central Study Contacts

Peter LICHTLEN, M.D.

CONTACT

+41 (0)76 349 12 22contact@genfit.com

Peter Lichten, M.D.

CONTACT

866-899-1477pdl@lbpd-consulting.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2023

First Posted

May 24, 2023

Study Start

August 21, 2023

Primary Completion

May 1, 2026

Study Completion (Estimated)

October 1, 2026

Last Updated

January 22, 2026

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

US(10)PR(1)