Treatment of Atezolizumab and Derazantinib in Patients With Advanced iCCA With FGFR2 Fusions/Rearrangements

NCT05174650 | Active Not Recruiting Phase 2

• 1 other identifier: ADVANCE_2020
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 17

Brief Summary

The study trial is a open-label, single-arm, multicenter phase II trial investigating the combined treatment of atezolizumab and derazantinib in patients with advanced intrahepatic cholangiocarcinoma with FGFR2 fusions/rearrangements

Conditions

Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Primary Objective: Assessment of Efficacy

  Objective Response Rate (ORR) will be assessed every 8 weeks (+/- 7 days) according to RECIST 1.1 criteria

  up to 4 years, at EOS

Secondary Outcomes (4)

• Secondary Objective: Assessment of Safety

  up to 4 years, at EOS

• Secondary Objective: Assessment of Efficacy in relation to objection response rate at EOT

  up to 4 years, at EOS

• Secondary Objective: Assessment of Efficacy in relation to progression free survival

  up to 4 years, at EOS

• Secondary Objective: Assessment of Efficacy in relation to overall survival

  4 years, at EOS

Other Outcomes (2)

• Tertial Objective: Exploratory Biomarker Objective in Blood Samples

  4 years, at EOS

• Tertial Objective: Exploratory Biomarker Objective in Fecal Samples

  4 years, at EOS

Study Arms (1)

Combined treatment with Atezolizumab and Derazantinib

EXPERIMENTAL

Treatment with Atezolizumab 1200 mg i.v. every 3 weeks and Derazantinib 300 mp p.o. once daily for a maximum of 60 weeks or until disease progression or unacceptable toxicity or study termination

Drug: Atezolizumab; Drug: Derazantinib

Interventions

Atezolizumab DRUG

Infusion i.v. of atezolizumab on day 1 of a 3-week cycle, first infusion rate over 60 minutes, subsequent infusion rates 30 minutes if tolerated for a maximum of 20 cycles in total

Also known as: Tecentriq

Combined treatment with Atezolizumab and Derazantinib

Derazantinib DRUG

Oral intake of 300 mg derazantinib continuously on day 1 to day 21 of a 3-week cycle for a maximum of 20 cycles in total

Also known as: ARQ 087

Combined treatment with Atezolizumab and Derazantinib

Eligibility Criteria

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

You may qualify if:

• Patients must meet all of the following criteria to be eligible for the study:
• Fully informed written consent and locally required authorization (European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Patients\*, age ≥ 18 years at the time of signing the Informed Consent Form.
• Histologically documented diagnosis of non-resectable iCCA with positively confirmed FGFR2 fusion/rearrangement via NGS-Analysis.
• Note: Only CE-IVD marked NGS-tests are applicable which cover FGFR2 fusions and rearrangements.
• Performance status (PS) ≤ 2 (ECOG scale).
• At maximum one previous line of systemic anti-cancer therapy, (chemotherapy, hormonal, targeted therapy, experimental therapy) for which treatment was discontinued at least 4 weeks before the first dose of study treatment, or five half-lives of the respective anti-cancer therapy, whichever is the longer period.
• Note: For mABs in previous therapy the restriction to five half-lives does not apply.
• No prior treatment with any FGFR or immune checkpoint inhibitor (including but not limited to antiCTLA-4, antiPD-1, and antiPD-L1 therapeutic antibodies) apart from Durvalumab as PD-L1 inhibitor in first line therapy.
• Body weight \> 30 kg AND BMI ≥ 15.
• At least one measurable site of disease as defined by RECIST 1.1 criteria.
• Adequate bone marrow and renal function including the following:
• Hemoglobin ≥ 9.0 g/dL (previous transfusion permitted);
• Absolute neutrophil count (ANC) ≥ 1.500 per µL (1.5×109/L);
• Platelet count ≥ 75,000 per µL (75 × 109/L);

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Mixed cholangiocarcinoma and HCC.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) study or a study without a medical intervention (specifically the PLATON registry \[ClinicalTrials.gov identifier: NCT04484636\] is allowed).
• Note: After the Safety Follow-up (28 days post treatment discontinuation) participation in another clinical study is allowed.
• Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery.
• Note: Local non-major surgery for palliative intent (e.g. surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious active, uncontrolled, gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of IMP and of low potential risk for recurrence;
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
• Adequately treated carcinoma in situ without evidence of disease.
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 5 months after the last dose of combination therapy or for a period of at least 5 half-lives of the respective drug/IMP after the last dose of combination therapy (whichever is longer).
• Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the product.
• Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study.
• Active or History of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

Sponsors & Collaborators

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

Study Sites (17)

HELIOS KLinikum Bad Saarow

Bad Saarow, Germany

Location

MVZ am Oskar-Helene Heim Berlin

Berlin, Germany

Location

Universitätsmedizin Berlin Charité

Berlin, Germany

Location

Vivantes Klinikum Berlin Friedrichshain

Berlin, Germany

Location

Johanniter Krankenhaus Bonn

Bonn, Germany

Location

Uniklinikum Köln

Cologne, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, Germany

Location

Krankenhaus Nordwest gGmbH

Frankfurt, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Alexianer Krefeld GmbH

Krefeld, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Germany

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

LMU München Großhadern

Munich, Germany

Location

Klinikum rechts der Isar, Technische Universität München

München, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Marienhospital Wesel

Wesel, Germany

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

atezolizumab; derazantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

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

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: January 3, 2022
• Study Start: April 20, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (17)