Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

LUD2015-005

This is an open-label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D/D2).

2016-06-24

2022-06-16

2022-06-16

Completed

Early phase I

73

Inclusion Criteria: 1. Histological diagnosis of oesophageal or gastrooesophageal cancer and have not received prior chemotherapy. * Cohorts A and B - metastatic/locally advanced cancer * Cohorts C/C-FLOT and D/D2 - deemed suitable for surgery with curative intent 2. Anticipated lifespan greater than 4 months. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and: * at least 8 weeks without tumour progression after any whole brain radiotherapy * at least 4 weeks since craniotomy and resection or stereotactic radiosurgery * at least 3 weeks without new brain metastases as evidenced by MRI/CT 5. Adequate normal organ and marrow function. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted. 6. Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements. 7. Age 18 years or older. Exclusion Criteria 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study. 2. Participation in another clinical study with an investigational product during the last 4 weeks. 3. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction. 4. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). 5. History of allogeneic organ transplant. 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. 7. Known history of previous clinical diagnosis of tuberculosis. 8. History of pneumonitis or interstitial lung disease.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 73, 'type': 'ACTUAL'}}

2024-03-22