IMMUWHY

Phase 1

Recruiting

• Conditions: Advanced stage intrahepatic biliary tract cancer (BTC); MedDRA version: 20.0Level: LLTClassification code: 10073077Term: Intrahepatic cholangiocarcinoma Class: 10029104; MedDRA version: 20.0Level: LLTClassification code: 10008594Term: Cholangiocarcinoma non-resectable Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508314-42-00
• Lead Sponsor: Institut fuer Klinische Krebsforschung IKF GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-19
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Fully-informed written consent and locally required authorization (European Union [EU]: General Data Privacy Regulation (GDPR)) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations., Adequate hepatic function (with stenting for any obstruction, if required) including the following: o Serum bilirubin = 1.5 x institutional upper limit of normal (ULN); o AST (SGOT) / ALT (SGPT) = 2.5x institutional ULN (NOTE: if liver metastases are present AST / ALT must be = 5x institutional ULN; o prothrombin time ?60%; o albumin ?30 g/L., Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial., Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: o Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). o Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)., The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations., Must have a life expectancy of at least 12 weeks., If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria: - Patients with HBV or HCV infection should be monitored for viral levels during study participation. - Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA < 100 IU/ml and should be managed per local treatment guidelines. Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the time point of enrollment into the study by the latest and treatment is continued during study participation and for = 6 months after end of study treatment. - HCV patients with advanced BTC are mostly not treated for their HCV infection. However, patients treated for HCV are considered suitable for inclusion if antiviral therapy has been completed = 30 days prior to first administration of study drug., Age = 18 years., Histologically documented diagnosis of locally-advanced OR limited metasized intrahepatic BTC not amenable to curative treatment (tumor resection or ablation), specified as • Tumor being confined to the liver or • In case of presence of extrahepatic lesions, metastasis must be stable AND of limited extent*AND patient must have a potential benefit from study participation in comparison to standard of care systemic therapy per local tumor board evaluation. *Limited extent is defined in this protocol as presence of o EITHER =3 malignant extrahepatic lymph nodes (short axis diamete

Exclusion Criteria

Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study., Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, , 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 non-infectious pneumonitis requiring steroids, or patients with Grade = 2 pneumonitis., History of another primary malignancy except for: o Malignancy treated with curative intent and with no known active disease = 5 years before the first dose of IP and of low potential risk for recurrence o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease o Adequately treated carcinoma in situ without evidence of disease, History of leptomeningeal carcinomatosis, Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry., History of active primary immunodeficiency, History of allogenic organ transplantation., Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies) or active hepatitis B/hepatitis C co-infection., Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion: o Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection) o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent o Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication), Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of durvalumab., Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment., 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., Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG., Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG]., Receipt of live attenuated vaccine within 30 days prior to the first administration of any of the IMPs and without need to receive any live attenuated vaccines during study conduct and for up to 30 days after end of Durvalumab treatment or 90 days after end of Tremelimumab treatment respectively., Prior immun

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the anti-tumor activity of durvalumab or durvalumab and tremelimumab administered after standard-of-care SIRT in patients with unresectable intrahepatic biliary tract cancer as measured by the objective response rate (ORR).;Secondary Objective: To assess safety of the combined treatment in the two treatment arms., To assess the efficacy of durvalumab or durvalumab and tremelimumab administered after standard-of-care SIRT in patients with unresectable intrahepatic biliary tract cancer as measured by duration of response (DoR), progression free survival (PFS) and overall survival (OS)., Exploratory objective: To assess predictive biomarkers for ORR, DoR, PFS and OS in tumor tissue and blood samples.;Primary end point(s): Objective response rate (ORR) [according to RECIST 1.1]

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Safety (rate of adverse events);Secondary end point(s):Duration of response (DoR);Secondary end point(s):Progression free survival (PFS);Secondary end point(s):Overall survival (OS);Secondary end point(s):Exploratory: Predictive biomarkers for ORR, DoR, PFS, OS