Advanced non-resectable intrahepatic cholangiocarcinoma with positively confirmed FGFR2 fusion/rearrangements via NGS-Analysis MedDRA version: 27.0 Level: PT Classification code 10008593 Term: Cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts
Conditions
Interventions
Trade Name: Tecentriq® 1.200 mg
Pharmaceutical Form: Concentrate for solution for infusion
Product Name: Derazantinib
Product Code: Derazantinib•2HCl / BAL087 / BAL0000087-001
Pharmaceutical Form: Ca
Sponsors
Frankfurter Institut für Klinische Krebsforschung IKF GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be eligible for the study: 1. 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. 2. Patients*, age = 18 years at the time of signing the Informed Consent Form. 3. 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. 4. Performance status (PS) = 2 (ECOG scale). 5. 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. 6. 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. 7. Body weight > 30 kg AND BMI = 15. 8. At least one measurable site of disease as defined by RECIST 1.1 criteria. 9. 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);International normalized ratio (INR) between 0.8 × ULN to 1.0 × ULN OR = 3 × ULN for subjects receving anticoagulant therapy Creatinine = 1.5 × ULN OR CLCR = 50 mL/min (as calculated by the Cockcroft-Gault formula);serum phosphate = ULN;corrected serum calcium = 1.75 mmol/L (= 7.0 mg/dL) AND = 3.1 mmol/L (= 12.5 mg/dL); serum sodium = LLN. 10. Adequate hepatic function (with stenting for any obstruction, if required) including the following:Total bilirubin = 2 × ULN; AST or ALT = 3 × ULN (or = 5 × ULN for subjects with liver metastases); Prothrombin time = 60%; Albumin = 2.8 g/dL. 11. For patients with active hepatitis B virus (HBV): HBV DNA = 500 IU/mL obtained within 28 days prior to initiation of study treatment, AND Anti-HBV treatment (per local standard of care; e.g., entecavir) prior to study entry and willingness to continue treatment for the length of the study. 12. For patients with active hepatitis C virus (HCV): • Patients positive for hepatitis C virus (HCV) antibody are eligible, also if polymerase chain reaction testing is positive for HCV ribonucleic acid (RNA). • However, anti-viral therapy against HCV is only allowed prior to trial but not during the trial. 13. Negative HIV test. 14. Negative pregnancy test within 72 h prior to dosing. 15. Females 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 5 months or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) after the last study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (has not had = 12 continuous months of amenorrhea with no identified cause other than menopause), and has
Exclusion criteria
Exclusion criteria: 1. Mixed CCA and HCC. 2. 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). 3. 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. 4. Uncontrolled intercurrent illness (as described in the study protocol). 5. History of another primary malignancy (with a few exceptions, as described in the study protocol). 6. 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). 7. Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the product. 8. 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. 9. 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. 10. History of non-infectious pneumonitis requiring steroids, or patients with Grade = 2 pneumonitis. 11. History of active primary immunodeficiency. 12. History of allogeneic bone marrow transplantation or prior solid organ transplantation. 13. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment (with two exceptions, as described in the study protocol). 14. Administration of a live, attenuated vaccine within four weeks or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab. 15. Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmias, unstable angina, and/or concurrent and clinically significant abnormalities on electrocardiogram (ECG) at Screening, including QTcF > 450 ms for males or > 460 ms for females. 16. Clinically significant valvular defect. 17. Unable or unwilling to swallow the complete daily dose of derazantinib capsules. 18. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease > 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications). 19. Current evidence of clinically significant corneal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective of the study is to assess the efficacy of atezolizumab in combination with derazantinib by ORR (Objective Response Rate) after 9 months of study treatment as assessed by the local investigator according to RECIST 1.1 criteria.;Secondary Objective: - To assess the efficacy of atezolizumab in combination with derazantinib by ORR (Objective Response Rate) at EOT (End Of Treatment), PFSR (Progression Free Survival Rate) at 6, 8 and 10 months, PFS (Progression Free Survival) and OS (Overall Survival) - To evaluate the safety and tolerability of atezolizumab in combination with derazantinib - To evaluate biomarkers in tumor tissue and blood samples for their predictive and prognostic potential;Primary end point(s): Objective Response Rate (ORR) assessed every 8 weeks 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. ;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - ORR (Objective Response Rate) at EOT (End of Treatment) - PFSR (Progression Free Survival Rate) at 6, 8 and 10 months - PFS (Progression Free Survival) - OS (Overall Survival) - Safety endpoints: incidence of adverse events, serious adverse events and adverse events of special interest; severity of adverse events by CTCAE v5.0 grade; relationship of adverse events to atezolizumab and/ or derazantinib; frequency of clinically significant abnormal laboratory parameters - Serum Tumor Markers (CA19-9, CEA) as efficacy measurements - Exploratory endpoints: fecal samples for microbiom analysis and blood samples for accompanying research project;Timepoint(s) of evaluation of this end point: - End of study - Safety will be evaluated continuously and after end of study | — |
Countries
Germany
Contacts
Public ContactProject Management
Frankfurter Institut für Klinische Krebsforschung IKF GmbH
Outcome results
None listed