A Phase II Single-arm, Open-label Study of Atezolizumab and Derazantinib for Patients With Advanced Intrahepatic Cholangiocarcinoma With FGFR2
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Intrahepatic Cholangiocarcinoma
- Sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Enrollment
- 27
- Locations
- 17
- Primary Endpoint
- Primary Objective: Assessment of Efficacy
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
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
Detailed Description
The aim of this phase II study is to explore the safety and anti-tumor efficacy of the combination of atezolizumab and derazantinib in patients with advanced intrahepatic cholangiocarcinoma, with ORR as the primary endpoint. The primary endpoint is the Objective Response Rate (ORR \[assessed every 8 weeks (±7 days)\]): Objective response rate (ORR) according to investigator-based RECIST 1.1 assessment, defined as the proportion of allocated subjects with best response of complete or partial response within 9 months after the date of first administration of study treatment. The secondary endpoints are safety and efficacy and will be evaluated by * Incidence, treatment relationship, seriousness, and severity of all AEs, SAEs, AESIs according to CTCAE V5.0 * ORR@EOT: Objective response rate (ORR) according to investigator-based RECIST 1.1 assessment, defined as the proportion of allocated subjects with best response of complete or partial response within study treatment. • PFSR@6, 8 and 10 months: The proportion of patients known to be alive and without confirmed objective disease progression at 6, 8 and 10 months after first administration of study treatment, respectively. • PFS: Time from first administration of study treatment until the date of first objective disease progression or death. • OS: Time from first administration of study treatment until death of a patient due to any cause
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 ≥
Exclusion Criteria
- •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;
Arms & Interventions
Combined treatment with Atezolizumab and Derazantinib
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
Intervention: Atezolizumab
Combined treatment with Atezolizumab and Derazantinib
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
Intervention: Derazantinib
Outcomes
Primary Outcomes
Primary Objective: Assessment of Efficacy
Time Frame: up to 4 years, at EOS
Objective Response Rate (ORR) will be assessed every 8 weeks (+/- 7 days) according to RECIST 1.1 criteria
Secondary Outcomes
- Secondary Objective: Assessment of Safety(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 objection response rate at EOT(up to 4 years, at EOS)
- Secondary Objective: Assessment of Efficacy in relation to overall survival(4 years, at EOS)