Phase I, Open Label, Dose Escalating Study to Investigate Safety and Tolerability of Intravesical Application of Trifunctional Anti-EPCAM x Anti-CD3 Antibody Catumaxomab in Patients With Non-muscle Invasive Bladder Cancer (NMIBC)

Lindis Biotech GmbH1 site in 1 country30 target enrollmentJuly 7, 2020

ConditionsUrinary Bladder Neoplasms

InterventionsCatumaxomab

DrugsCatumaxomab

Overview

Phase: Phase 1
Intervention: Catumaxomab
Conditions: Urinary Bladder Neoplasms
Sponsor: Lindis Biotech GmbH
Enrollment: 30
Locations: 1
Primary Endpoint: Incidence and severity of treatment related adverse events
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of the study is to investigate the safety, tolerability, and preliminary efficacy of the monoclonal bispecific trifunctional antibody Catumaxomab in patients with non-muscle invasive bladder cancer (NMIBC).

Detailed Description

The present Phase I dose escalation study (CATUNIBLA) in patients with non-muscle invasive bladder cancer (NMIBC) of high and intermediate risk for progression aims at investigating the therapeutic potential of Catumaxomab applied as intravesical instillation. Catumaxomab is an intact trifunctional bispecific monoclonal antibody and has the molecular targets EpCAM and CD3. It mediates antibody-dependent cellular cytotoxicity against human epithelial tumor cells including bladder cancer. The study consists of two parts: Part I is dose finding and will investigate 3 sequential cohorts consisting of 3 patients to be enrolled at the specified dose levels. After determination of the dose for Part II an additional number (n=X) of patients will be included at this dose level. Part I and part II have a screening period, 6 week treatment phase and a follow-up phase.

Registry

clinicaltrials.gov

Start Date

July 7, 2020

End Date

December 30, 2023

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Lindis Biotech GmbH

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients will be enrolled in this Phase I study only if they meet all of the following criteria:
•Male or non-pregnant, non-breastfeeding female, age 18 years or older at date of consent.
•Any of the following histologically confirmed non-muscle invasive urothelial carcinoma of the bladder:
•High-risk tumors according to EAU guidelines:
•G3 HG tumors
•Multiple, recurrent and large (\>3cm) pTa G1-G2 LG tumors (all features must be present)
•Patients of the subgroup of highest risk tumours (T1G3/HG associated with concurrent bladder CIS, multiple- and/or large T1G3/HG and/or recurrent T1G3/HG, T1G3/HG with CIS in the prostatic urethra, some forms of variant histology of urothelial carcinoma, lymphovascular invasion) will be only enrolled if they have already failed BCG-treatment or they cannot tolerate it and are ineligible or refuse cystectomy. In the Part II of the study a minimal expression of EpCAM in the tumor tissue may be required, based on preliminary evidence from the Part I of the study
•Previous therapies must be discontinued at least 2 weeks prior to administration of Catumaxomab and all treatment related toxicities must have resolved or decreased to common toxicity criteria (CTCAE) grade
•Time period from primary resection to antibody treatment start must be at least one week and should not exceed 2 weeks.
•Any investigational agent must be discontinued at least 4 weeks or 5 half-lives, whichever is longer, prior to antibody treatment start.

Exclusion Criteria

•Patients will not be enrolled in this Phase I study if they meet any of the following criteria:
•The female patient is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
•Low risk or intermediate risk tumors according to EAU guidelines
•History or signs (obstruction of upper urinary tract or cross hematuria in the ureteral orifice) of urethral or upper tract transitional cell carcinoma (TCC). Patients with T1 disease of the bladder must have no evidence of upper or lower tract disease or a more advanced stage of disease by either computed tomography (CT) urography or magnetic resonance imaging (MRI) urography of the abdomen and pelvis performed within 8 weeks before the first application of study treatment. If intravenous contrast medium for CT and MRI is contraindicated, retrograde ureteropyelography, or CT or MRI without intravenous contras tmedia may be performed.
•Patients with hydronephrosis.
•Any intravesicular or other chemotherapy treatment within 2 weeks or any investigational agent within 4 weeks or 5 half-lives of the agent whatever is longer prior to the initial dose of study drug
•History of recurrent severe urinary tract infections (UTIs) per investigator judgment.
•Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the opinion of the investigator, would predispose the patient to the development of complications from the administration of intravesical therapy.
•A diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy within the next 2 years i.e., while the patient may be taking study treatment or is in the follow up period of this study.
•Patients with a history of cancer who have completed treatment and are free from disease since at least 5 years can be enrolled.

Arms & Interventions

Catumaxomab

intravesical Catumaxomab instillation

Intervention: Catumaxomab

Outcomes

Primary Outcomes

Incidence and severity of treatment related adverse events

Time Frame: approximately 2.5 years after study start

Incidence and severity of treatment related adverse events during intravesical instillation with catumaxomab are observed according to NCI CTCAE, Version 5.0

Dose escalation phase to evaluate DLT incidence

Time Frame: approximately 1 year after study start

Dose Limited Toxicity

Secondary Outcomes

Anti-drug antibodies (ng/ml)(approximately 2.5 years after study start)
Number of EpCAM-positive tumor cells in the urine(approximately 2.5 years after study start)
Number of immune cells in the urine(approximately 2.5 years after study start)
Cmin (ng/ml)(approximately 2.5 years after study start)
Tmax (hours)(approximately 2.5 years after study start)
Cytokines (pg/mL)(approximately 2.5 years after study start)
AUC (day * ng/ml)(approximately 2.5 years after study start)
Cmax (ng/ml)(approximately 2.5 years after study start)
t1/2 (days)(approximately 2.5 years after study start)
Local progression free interval(approximately 2.5 years after study start)
Identification and quantification of tumor cells in urine(approximately 2.5 years after study start)
Complete response(approximately 2.5 years after study start)
EpCAM expression(approximately 2.5 years after study start)
Antitumor activity(approximately 2.5 years after study start)
Recurrence-free interval(approximately 2.5 years after study start)