Evaluation of Sacituzumab Govitecan in Metastatic Esophagogastric Adenocarcinoma: A Phase Ib/II Single-Arm Multicenter Study

Trial ID: 2023-505257-40-00
Protocol: SAGA
Sponsor: Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

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Diseases & Conditions

Oesophageal adenocarcinoma

Objectives

The primary objective of this study is to evaluate the **efficacy** of sacituzumab-govitecan in patients with **metastatic esophagogastric adenocarcinoma**. This is clinically relevant as metastatic esophagogastric adenocarcinoma represents an advanced stage of cancer with limited treatment options, and assessing the efficacy of new therapeutic agents is crucial for improving patient outcomes. Sacituzumab-govitecan is a TROP-2 targeting antibody linked with SN38, and its potential to provide therapeutic benefits in this patient population is the focus of this investigation.

Participants

The clinical trial focuses on evaluating the efficacy of **sacituzumab-govitecan** for patients diagnosed with **metastatic esophagogastric adenocarcinoma (Stage IV)**. The study population includes both male and female participants, aged 18 years and older, who have been previously treated with a platinum compound and a fluoropyrimidine in the metastatic setting. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial includes individuals with adequate hematological, hepatic, and renal function, and an estimated life expectancy of at least 12 weeks. Participants must be willing to provide liquid biopsy samples for the translational research program. The sponsor has not provided information regarding the total number of participants in the trial. The trial population was selected based on specific inclusion criteria, ensuring that participants are capable of complying with the study protocol and have given written informed consent. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to contraceptive guidelines if applicable. The trial also includes a vulnerable population, although specific details are not disclosed.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **sacituzumab govitecan** in patients with **metastatic esophagogastric adenocarcinoma**. This is a phase Ib/II single-arm, multicenter study. The trial is not randomized, and it does not employ a double-blind or controlled design. The estimated duration of the trial is from September 1, 2023, to March 31, 2027. Participants will be involved in the study for the duration of their treatment, with the possibility of early termination if they do not comply with the study protocol or if they experience adverse effects that necessitate withdrawal.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, diagnosis, prior treatment history, and overall health status. Participants must have a histologically confirmed diagnosis of stage IV metastatic esophagogastric adenocarcinoma and meet specific hematological, hepatic, and renal function parameters. Following the screening, participants will undergo regular follow-up visits to monitor their response to the treatment and any side effects. The primary endpoint of the study is the overall response rate, which includes complete and partial responses. The end-of-study visit will occur after the completion of the treatment regimen or upon early termination from the study.

Participants are required to provide written informed consent and agree to use effective contraceptive methods during the study and for six months after the last treatment. The study involves the administration of sacituzumab govitecan via intravenous infusion, and participants must be willing to provide liquid biopsy samples for translational research purposes. The trial aims to explore the therapeutic potential of sacituzumab govitecan, a TROP-2 targeting antibody linked with SN38, in this patient population.

Treatment

The clinical trial involves the administration of **sacituzumab govitecan**, an investigational medication designed for the treatment of metastatic esophagogastric adenocarcinoma. Sacituzumab govitecan is a **TROP-2 targeting antibody** conjugated with SN38, a potent topoisomerase I inhibitor. The pharmaceutical form of sacituzumab govitecan is a powder for concentrate for solution for infusion. The medication is administered via **intravenous infusion**. The specific dosage, frequency of administration, and treatment duration are determined according to the study protocol, which is not detailed in the provided data. The investigational product is not a pediatric formulation and is labeled specifically for the study.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The study is a single-arm design, focusing solely on the efficacy of sacituzumab govitecan. Participant compliance with the dosing schedule is monitored as per the trial's standard operating procedures, although specific compliance measures are not detailed in the provided information. The investigational product is not classified as an orphan drug, and there are no additional medicinal products listed for use in conjunction with sacituzumab govitecan in this study.

Efficacy

The efficacy of **sacituzumab govitecan** in the treatment of metastatic esophagogastric adenocarcinoma will be assessed in this phase Ib/II clinical trial. The primary endpoint for evaluating efficacy is the Overall Response Rate (ORR), which includes both complete response (CR) and partial response (PR) to the treatment. This endpoint will provide a measure of the proportion of patients who experience a significant reduction in tumor size or complete disappearance of the tumor as a result of the therapy.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patient has given written informed consent.
Patient is, in the investigator’s judgement, willing and able to comply with the study protocol.
Patient is ≥ 18 years of age at time of signing the written informed consent.
Patient has been diagnosed with histologically confirmed metastatic (stage IV) esophagogastric adenocarcinoma.
Patient has received a prior therapy containing platinum compound and a fluoropyrimidine in the metastatic setting. Neoadjuvant/adjuvant platinum-fluoropyrimidine treatment is counted as first-line therapy if disease progression occurred within 6 months after completion of treatment.
Patient has an ECOG performance status ≤ 1.
Patient must have an estimated life expectancy of at least 12 weeks.
Patient has adequate hematological, hepatic and renal function as indicated by the following parameters: a. Leukocytes ≥ 2,500/μL, platelets ≥ 100,000/μL without transfusion, absolute neutrophil count (ANC) ≥ 1,500/μL without granulocyte colony-stimulating factor support, hemoglobin ≥ 90 g/L (9 g/dL) - Patients may be transfused to meet this criterion. b. Bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase and alanine transaminase ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases), alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases) c. Serum creatinine ≤ 1.5 x ULN, or glomerular filtration rate > 45 mL/min (calculated per institutional standard) d. Serum albumin ≥ 25 g/L (2.5 g/dL) e. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN; for patients receiving therapeutic anticoagulation: stable anticoagulant regimen
Patient must be willing to provide liquid biopsy samples for the translational research program.
Female patients of childbearing potential and male patients with female partners 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 6 months after the last study treatment. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.

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Exclusion Criteria

Patient has known hypersensitivity to any component of the Sacituzumab-govitecan formulation as well as a known history of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
Patient has received previously topoisomerase 1 inhibitors such as irinotecan, or nal-irinotecan
Patient has an active second malignancy. Note: patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (e.g., non-melanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll
Patient meets any of the following criteria for cardiac disease: a. Myocardial infarction or unstable angina pectoris within 6 months prior to initiation of study treatment b. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular bock, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation c. New York Heart Associated (NYHA) class III or greater congestive heart failure or left ventricular ejection fraction (LVEF) of < 40% if echocardiography has been performed
Patient has an active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months prior to initiation of study treatment
Patient has an active serious infection requiring antibiotic treatment
Patient has known history of human immune deficiency virus (HIV, or positive HIV antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism
Patient has active hepatitis B or C virus (HBV/HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded
Patient participated in another interventional clinical study ≤ 14 days prior to initiation of study treatment or at the same time as this study.
Patient has taken an investigational drug within 14 days or 5 half-lives (whichever is longer) prior to initiation of study treatment.
Patient received anticancer biologic agent within 28 days or targeted small molecule, radiation or chemotherapy within 14 days prior to initiation of the study treatment.
Patient has not recovered from AEs due to previously administered drug (i.e., ≥ grade 2 is concerned as not recovered) a. Patients with any grade of alopecia are an exception to this criterion and will qualify for the study b. If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.
Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.