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

NCT06856837 | Recruiting Phase 2 DMC

• 1 other identifier: QUINTIS
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 23

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of Fruquintinib in combination with the PD-1 inhibitor Tislelizumab in MSS/pMMR metastatic colorectal cancer without liver metastases.

  Progression-free survival (PFS), defined as time from randomization until date of progression acc. to RECIST v1.1 or death due to any cause.

  up to 54 month

Secondary Outcomes (6)

• Overall survival

  up to 54 month

• Objective response rate

  up to 54 month

• Disease control rate

  up to 54 month

• Duration of response

  up to 54 month

• To evaluate the safety and tolerability of Fruquintinib in combination with the PD-1 inhibitor Tislelizumab in MSS/pMMR metastatic colorectal cancer without liver metastases.

  up to 54 month

Other Outcomes (1)

• Exploratory Translational Objectives

  up to 54 month

Study Arms (2)

Arm A

EXPERIMENTAL

* 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 \[Q6W\])

Drug: Fruquintinib; Drug: Tislelizumab

Arm B

ACTIVE COMPARATOR

* 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 \[Q2W\])

Drug: Trifluridine/tipiracil; Drug: Bevacizumab

Interventions

Fruquintinib DRUG

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

Also known as: Fruzaqla

Arm A

Tislelizumab DRUG

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

Also known as: Tevimbra

Arm A

Trifluridine/tipiracil DRUG

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

Also known as: Lonsurf

Arm B

Bevacizumab 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)

Also known as: Avastin

Arm B

Eligibility Criteria

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

You may qualify if:

• Patient\* provide signed informed consent form.
• Patient is ≥ 18 years at the time of given informed consent.
• 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.
• 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.
• 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.
• 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.
• Patient has an ECOG performance status ≤ 1.
• Patient has a life expectancy \> 16 weeks.
• Patient has adequate hematological, hepatic and renal function.
• Absolute number of neutrophils (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• 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)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN, AP ≤ 5 x ULN
• 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).
• 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)

You may not qualify if:

• Patient has known allergic / hypersensitive reactions to at least one of the treatment components
• 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
• Patient received previous treatment with Fruquintinib, trifluridine/tipiracil, regorafenib or an anti-PD-1/anti-PD-L1 antibodies.
• 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.
• Patient receives simultaneous treatment with a different anti-cancer therapy other than that provided for in the trial (excluding palliative radiotherapy for symptom control).
• Patient has known untreated or symptomatic CNS or leptomeningeal metastases.
• 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.
• Patient has history of uncontrolled infection with human deficiency virus (HIV) or chronic infection with hepatitis B or C virus (HBV, HCV).
• Patient has evidence of bleeding diathesis.
• Patient has history of gastrointestinal perforation or fistulae in past 6 months or risk factors for perforation.
• Patient has grade 3-4 gastrointestinal bleeding within 3 months prior to first dose of trial therapy.
• 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).
• Patient had a major surgery within 2 weeks prior to first dose of trial therapy.
• 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.
• 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.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (23)

Ordensklinikum Linz GmbH

Linz, Austria

NOT YET RECRUITING

SCRI CCCIT Ges.m.b.H.

Salzburg, Austria

RECRUITING

Noe LGA Gesundheit Thermenregion GmbH

Wiener Neustadt, Austria

NOT YET RECRUITING

Klinikum St. Marien Amberg

Amberg, Germany

RECRUITING

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

RECRUITING

Charite Universitaetsmedizin Berlin KöR

Berlin, Germany

RECRUITING

HELIOS Emil von Behring Berlin

Berlin, Germany

RECRUITING

Katholisches Klinikum Bochum gGmbH

Bochum, Germany

NOT YET RECRUITING

Universitätsklinikum Düsseldorf Klinik für Gastroenterologie, Hepatologie und Infektiologie Gastroonkologische Studienzentrale

Düsseldorf, 40225, Germany

NOT YET RECRUITING

KEM | Klinik für Internistische Onkologie gGmbH

Essen, 45136, Germany

RECRUITING

Universitätsklinikum Essen

Essen, 45147, Germany

NOT YET RECRUITING

Goethe University Frankfurt

Frankfurt, Germany

RECRUITING

Institut für Klinisch-Onkologische Forschung am Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

RECRUITING

Hamburg Hämatologisch-Onkologische Praxis Eppendorf-Facharztzentrum Eppendorf

Hamburg, 20246, Germany

RECRUITING

Asklepios Kliniken Hamburg GmbH

Hamburg, Germany

NOT YET RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

Marienhospital Herne

Herne, Germany

RECRUITING

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, 76137, Germany

NOT YET RECRUITING

Klinikum der Universität München AöR

München, Germany

RECRUITING

Klinikum rechts der Isar TU München

München, Germany

RECRUITING

Leopoldina Krankenhaus Schweinfurt

Schweinfurt, Germany

RECRUITING

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; tislelizumab; trifluridine tipiracil drug combination; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

• Alexander Stein, Prof. Dr.

  Hämatologisch-Onkologische Praxis Eppendorf University Cancer Center Hamburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Stein, Prof. Dr.

CONTACT

+494036035220; stein@hope-hamburg.de

Martin Walker

CONTACT

+4969589978772; walker.martin@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: March 4, 2025
• Study Start: October 27, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); DE (20)