A phase Ib/II single-arm, multicenter study of sacituzumab-govitecan, a TROP-2 targeting antibody linked with SN38, for patients with metastatic esophagogastric adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut fuer Klinische Krebsforschung IKF GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Apr 2024 → 7 Jan 2026

Decision date (initial)

2024-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GILEAD

External identifiers

EU CT number

2023-505257-40-00

ClinicalTrials.gov

NCT06123468

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The objective of the trial is to evaluate the efficacy of sacituzumab-govitecan for metastatic esophagogastric adenocarcinoma

Conditions and MedDRA coding

metastatic esophagogastric adenocarcinoma (Stage IV)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient has given written informed consent.
2. Patient is, in the investigator’s judgement, willing and able to comply with the study protocol.
3. Patient is ≥ 18 years of age at time of signing the written informed consent.
4. Patient has been diagnosed with histologically confirmed metastatic (stage IV) esophagogastric adenocarcinoma.
5. 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.
6. Patient has an ECOG performance status ≤ 1.
7. Patient must have an estimated life expectancy of at least 12 weeks.
8. 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
9. Patient must be willing to provide liquid biopsy samples for the translational research program.
10. 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.

Exclusion criteria 14

1. 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.
2. Patient has received previously topoisomerase 1 inhibitors such as irinotecan, or nal-irinotecan
3. 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
4. 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
5. 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
6. Patient has an active serious infection requiring antibiotic treatment
7. 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
8. 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
9. Patient participated in another interventional clinical study ≤ 14 days prior to initiation of study treatment or at the same time as this study.
10. Patient has taken an investigational drug within 14 days or 5 half-lives (whichever is longer) prior to initiation of study treatment.
11. 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.
12. 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
13. 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.
14. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR; complete response [CR] + partial response [PR])

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut fuer Klinische Krebsforschung IKF GmbH

Sponsor organisation

Institut fuer Klinische Krebsforschung IKF GmbH

Address

Steinbacher Hohl 2-26, Praunheim Praunheim

City

Frankfurt Am Main

Postcode

60488

Country

Germany

Scientific contact point

Organisation

Institut fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical Trial project manager

Public contact point

Organisation

Institut fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical Trial project manager

Third parties 3

Locations

2 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications