- IKF/AIO-QUINTIS - Evaluating Fruquintinib in Combination With Tislelizumab in Microsatellite Stable / Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Cancer Without Active Liver Metastases

NCT ID: NCT06856837

Last Updated: 2025-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-27

Study Completion Date

2029-12-31

Brief Summary

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This is a prospective, randomized, open-label, multicenter phase II investigating the therapy of Fruquintinib in combination with Tislelizumab in patients with MSS/pMMR metastatic colorectal cancer without liver metastases.

Detailed Description

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Participants eligible for this trial will be randomized 1:1 into one of the two arms (Arm A and Arm B) stratified by: I) -Previous anti-angiogenic therapy (yes vs. no), II) BRAF/RAS mutation status (wildtype vs. mutation) or III) History of liver metastases (never vs. prior but treated).

Patients in Arm A (experimental arm) will receive Fruquintinib (orally, 5 mg once a day, at day 1-21 of each 28-day cycle \[Q4W\]) plus Tislelizumab (i.v., 400 mg, at day 1 of each 42-day cycle \[Q6W\]).

Patients in Arm B (control arm) will receive Trifluridine/tipiracil (orally, 35 mg/m2 twice a day, day 1-5 and day 8-12 of each 28-day cycle \[Q4W\]) plus Bevacizumab (i.v., 5 mg/kg, at day 1 of each 14-day cycle \[Q2W\]).

The treatment will be performed until disease progression, unacceptable toxicity, patients' request, or end of protocol-defined treatment time (maximum of 15 months).

All patients will be followed up for a maximum of 18 months after last patient in or until death, withdrawal of consent or loss to follow-up, whatever occurs first.

Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants eligible for this trial will be randomized 1:1 into one of the two arms (experimental Arm A and control Arm B) stratified by: I) Previous anti-angiogenic therapy (yes vs. no), II) BRAF/RAS mutation status (wildtype vs. mutation), III) History of liver metastases (never vs. prior but treated)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

* Fruquintinib (orally, 5 mg once a day, at day 1-21 of each 28-day cycle \[Q4W\]) plus
* Tislelizumab (i.v., 400 mg, at day 1 of each 42-day cycle \[Q6W\])

Group Type EXPERIMENTAL

Fruquintinib

Intervention Type DRUG

highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3

Tislelizumab

Intervention Type DRUG

humanized immunoglobulin G4 (IgG4)-variant monoclonal antibody (mAb) against human programmed cell death-1 (PD-1)

Arm B

* Trifluridine/tipiracil (orally, 35 mg/m2 twice a day, day 1-5 and day 8-12 of each 28-day cycle \[Q4W\]) plus
* Bevacizumab (i.v., 5 mg/kg, at day 1 of each 14-day cycle \[Q2W\])

Group Type ACTIVE_COMPARATOR

Trifluridine/tipiracil

Intervention Type DRUG

trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor

Bevacizumab

Intervention Type DRUG

recombinant humanized anti-VEGF monoclonal antibody composed of human IgG1 framework regions and antigen-binding, complementarity-determining regions from a murine monoclonal antibody (muMAb VEGF A4.6.1)

Interventions

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Fruquintinib

highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3

Intervention Type DRUG

Tislelizumab

humanized immunoglobulin G4 (IgG4)-variant monoclonal antibody (mAb) against human programmed cell death-1 (PD-1)

Intervention Type DRUG

Trifluridine/tipiracil

trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor

Intervention Type DRUG

Bevacizumab

recombinant humanized anti-VEGF monoclonal antibody composed of human IgG1 framework regions and antigen-binding, complementarity-determining regions from a murine monoclonal antibody (muMAb VEGF A4.6.1)

Intervention Type DRUG

Other Intervention Names

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Fruzaqla Tevimbra Lonsurf Avastin

Eligibility Criteria

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Inclusion Criteria

1. Patient\* provide signed informed consent form.
2. Patient is ≥ 18 years at the time of given informed consent.
3. Patient has been diagnosed with histologically or cytologically proven microsatellite stable (MSS)/proficient mismatch repair (pMMR) metastatic adenocarcinoma of the colon or rectum, which is not amenable to potentially curative resection.
4. Known RAS (KRAS or NRAS) and BRAF V600E mutational status. Note: These mutations are mutually exclusive. Therefore, if one of the factors is mutated, it is not required to determine the mutation status of the others, as they are then assumed to be wildtype.
5. Patient without liver metastases (NLM) defined as subjects without active liver metastases at screening as determined on baseline imaging of the liver as performed by CT scan with contrast or MRI. Definitively treated liver metastases (which includes surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) that were treated at least 3 months prior to enrollment with no evidence of radiologic progression on subsequent imaging are considered to be non-active liver metastases.
6. Patient received at least one line of previous treatment with a fluoropyrimidine, oxaliplatin, irinotecan, VEGF(R) and if indicated EGFR and/or BRAF inhibitors in the advanced setting, or the patient has been intolerable or ineligible to those treatments.
7. Patient has an ECOG performance status ≤ 1.
8. Patient has a life expectancy \> 16 weeks.
9. Patient has adequate hematological, hepatic and renal function.

1. Absolute number of neutrophils (ANC) ≥ 1.5 x 109/L
2. Platelets ≥ 100 x 109/L
3. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (or \< 2 x ULN in case of prior liver involvement or Gilbert's disease)
4. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN, AP ≤ 5 x ULN
5. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (measured by 24 h urine) ≥ 30 mL/min (i.e., if serum creatinine level is \> 1.5 x ULN, then a 24-hour urine test must be performed to check the creatinine clearance to be determined).
6. Urinary protein ≤2+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥3+, a 24-hour urine collection for protein must demonstrate \<2000 mg of protein in 24 hours to allow participation in this protocol)
10. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).
11. Female patients of childbearing potential or male patients in Arm B with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 6 months after the last trial treatment. Male patients in Arm B with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy. Female patients of child-bearing potential must have a negative pregnancy test within the last 7 days prior to the start of trial therapy.
12. Patient is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

* There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the trial gender-independently.

Exclusion Criteria

1. Patient has known allergic / hypersensitive reactions to at least one of the treatment components
2. Patient had previous malignancy other than that under study within 3 years or concomitant malignancy, except: those with a 5-year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer
3. Patient received previous treatment with Fruquintinib, trifluridine/tipiracil, regorafenib or an anti-PD-1/anti-PD-L1 antibodies.
4. Patient receives current treatment with any anti-cancer therapy, such as systemic immunotherapy, chemotherapy, or hormone therapy within ≤ 2 weeks prior to study treatment start.
5. Patient receives simultaneous treatment with a different anti-cancer therapy other than that provided for in the trial (excluding palliative radiotherapy for symptom control).
6. Patient has known untreated or symptomatic CNS or leptomeningeal metastases.
7. Patient has impaired cardiac function or clinically significant cardiac disease including unstable angina within 6 months before the first dose of study treatment, acute myocardial infarction \< 6 months prior to the first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure \> 160 mmHg or diastolic \> 100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiring antiarrhythmic therapy other than beta blockers or digoxin, active coronary artery disease or corrected QT interval (QTc) ≥ 470.
8. Patient has history of uncontrolled infection with human deficiency virus (HIV) or chronic infection with hepatitis B or C virus (HBV, HCV).
9. Patient has evidence of bleeding diathesis.
10. Patient has history of gastrointestinal perforation or fistulae in past 6 months or risk factors for perforation.
11. Patient has grade 3-4 gastrointestinal bleeding within 3 months prior to first dose of trial therapy.
12. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug (see Appendix 4 for examples).
13. Patient had a major surgery within 2 weeks prior to first dose of trial therapy.
14. Patient experienced severe, life-threatening, or recurrent (Grade 2 or higher) immune-mediated adverse events (AEs) or infusion-related reactions including those that led to permanent discontinuation while on treatment with immune-oncology agents.
15. Patient received prior immunosuppressive therapy: immunosuppressive doses of systemic medications of \> 10 mg/day of prednisone or equivalent must be discontinued ≥ 2 weeks before the first dose of study treatment. Short courses of high dose corticosteroids and/or continuous low dose of prednisone (\< 10 mg/day) are permitted. In addition, inhaled, intranasal, intraocular, and/or joint injections of corticosteroids are allowed.
16. Patient has active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.
17. Patient has history of solid organ transplantation .
18. Patient has history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or history of stroke and/or transient ischemic attack within the last 12 months.
19. Patients has evidence of any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect.
20. Female patient is pregnant or breast feeding or planning to become pregnant within and up to 6 months after end of treatment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Salah-Eddin Al-Batran, Prof. Dr.

Role: STUDY_DIRECTOR

Frankfurter Institut für Klinische Krebsforschung IKF GmbH

Alexander Stein, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Hämatologisch-Onkologische Praxis Eppendorf University Cancer Center Hamburg

Locations

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Ordensklinikum Linz GmbH

Linz, , Austria

Site Status NOT_YET_RECRUITING

SCRI CCCIT Ges.m.b.H.

Salzburg, , Austria

Site Status RECRUITING

Noe LGA Gesundheit Thermenregion GmbH

Wiener Neustadt, , Austria

Site Status NOT_YET_RECRUITING

Klinikum St. Marien Amberg

Amberg, , Germany

Site Status RECRUITING

HELIOS Klinikum Bad Saarow

Bad Saarow, , Germany

Site Status RECRUITING

Charite Universitaetsmedizin Berlin KöR

Berlin, , Germany

Site Status RECRUITING

HELIOS Emil von Behring Berlin

Berlin, , Germany

Site Status RECRUITING

Katholisches Klinikum Bochum gGmbH

Bochum, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Düsseldorf Klinik für Gastroenterologie, Hepatologie und Infektiologie Gastroonkologische Studienzentrale

Düsseldorf, , Germany

Site Status NOT_YET_RECRUITING

KEM | Klinik für Internistische Onkologie gGmbH

Essen, , Germany

Site Status RECRUITING

Universitätsklinikum Essen

Essen, , Germany

Site Status NOT_YET_RECRUITING

Goethe University Frankfurt

Frankfurt, , Germany

Site Status RECRUITING

Institut für Klinisch-Onkologische Forschung am Krankenhaus Nordwest

Frankfurt am Main, , Germany

Site Status RECRUITING

Hamburg Hämatologisch-Onkologische Praxis Eppendorf-Facharztzentrum Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Asklepios Kliniken Hamburg GmbH

Hamburg, , Germany

Site Status NOT_YET_RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Marienhospital Herne

Herne, , Germany

Site Status RECRUITING

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, , Germany

Site Status NOT_YET_RECRUITING

Klinikum der Universität München AöR

München, , Germany

Site Status RECRUITING

Klinikum rechts der Isar TU München

München, , Germany

Site Status RECRUITING

Leopoldina Krankenhaus Schweinfurt

Schweinfurt, , Germany

Site Status RECRUITING

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Ulm

Ulm, , Germany

Site Status RECRUITING

Countries

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Austria Germany

Central Contacts

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Alexander Stein, Prof. Dr.

Role: CONTACT

+494036035220

Martin Walker

Role: CONTACT

+4969589978772

Facility Contacts

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Bernhard Doleschal, Dr.

Role: primary

Lukas Weiss, Prof. Dr.

Role: primary

Birgit Grünberger, Prof. Dr.

Role: primary

Ludwig Fischer von Weikersthal, Dr.

Role: primary

Daniel Pink, MD

Role: primary

Arndt Stahler, PD Dr.

Role: primary

Börge Arndt, Dr.

Role: primary

Anke Reinacher-Schick, Prof. Dr.

Role: primary

Christoph Roderburg, Prof. Dr.

Role: primary

Christian Müller, Dr.

Role: primary

Stefan Kasper, Prof. Dr.

Role: primary

Christine Koch, PD Dr.

Role: primary

Thorsten Götze, Prof.

Role: primary

Alexander Stein, Prof. Dr.

Role: primary

Dirk Arnold, Prof. Dr.

Role: primary

Joseph Tintelnot, Dr.

Role: primary

Amin Turki, PD Dr.

Role: primary

Alexander Kolov, Dr.

Role: primary

Sabrina Opatz, Dr.

Role: primary

Sylvie Lorenzen, Prof. Dr.

Role: primary

Stephan Kanzler, Prof.

Role: primary

Ameen Aslan, Dr.

Role: primary

Thomas Ettrich, Dr.

Role: primary

Other Identifiers

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QUINTIS

Identifier Type: -

Identifier Source: org_study_id

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