A multi-center Phase 2 study of neoadjuvant immunotherapy in combination with the anti-GDF-15 antibody visugromab (CTL-002) for the treatment of muscle invasive bladder cancer
- Conditions
- Muscle invasive bladder cancer set to undergo radical cystectomy who cannot receive orrefuse to receive cisplatin-based chemotherapyMedDRA version: 20.0Level: PTClassification code: 10005003Term: Bladder cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-513957-55-00
- Lead Sponsor
- CatalYm GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 30
Able to understand the purpose of the study, provide signed and dated informed consent prior to performing any protocol-related procedures (including Screening evaluations), and comply with the study procedures., If subject has Type II diabetes and receives metformin, metformin has to be replaced with other antidiabetic(s) prior to start of study treatment (at minimum 7 days prior to study baseline GDF-15 measurement) and for the whole study treatment duration., Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study treatment. Women of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression., All subjects, male and female, who are not surgically sterilized or postmenopausal as defined below, and subjects’ partners of childbearing potential must agree to use highly effective methods of contraception” during the study and for at least 5 months (5 times the predicted halflife of visugromab [CTL-002] in humans) after the last dose of study drug. Highly effective methods of contraception” are combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogenonly hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. The double-barrier method (synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, or postovulation), withdrawal (coitus interruptus), lactational amenorrhea method and spermicide only are NOT acceptable as highly effective methods of contraception.” Postmenopausal is defined as at least 12 months after last menstrual bleeding without an alternative medical cause (e.g., amenorrhea due to prior chemotherapy, anti-estrogens, or ovarian suppression), Age = 18 years, Histopathologically confirmed urothelial carcinoma. Subjects with mixed histologies are required to have a dominant (i.e., 50% at least) transitional cell pattern., Clinical stage T2-T4aN0M0 MIBC, as assessed by CT (mandatory), PET/CT, or mpMRI (both optional)., Ineligible for cisplatin therapy per modified Galsky criteria (Eastern Cooperative Oncology Group [ECOG] Performance Status 2 subjects are excluded): a. Subjects with CTCAE v4 grade = 2 audiometric hearing loss (Galsky Criteria). b. Subjects with CTCAE v4 grade = 2 peripheral neuropathy (Galsky Criteria). c. Creatinine clearance of < 60 mL/min but = 30 mL/min (measured by the Cockcroft Gault formula or 24-hour urine). d. New York Heart Association (NYHA) Class III heart failureOr, refuses cisplatin-based chemotherapy., Eligible for RC by the following: a. Fit and planned for RC according to local guidelines. b. Able to receive a minimum of 12 weeks of neoadjuvant treatment on study before date of scheduled RC., Pretreatment tumor material from TURBT (stored paraffin block) must be available for planned scientific analyses and stem from biopsy/removal of primary tumor within less than 3 months prior to study treatment initiation and contain at least 20% of tumor c
Pregnant or breastfeeding., QT interval corrected for heart rate using Fridericia’s formula interval = 470 ms regardless of sex., Any active autoimmune disease that requires systemic immunosuppressive treatments, for which (re-)activation may present a medical threat to the subject as per the Investigator’s assessment., Any history of non-infectious pneumonitis < 6 months prior to Screening., Any active inflammatory bowel disease such as Crohn’s disease or ulcerative colitis or active autoimmune thyroiditis, all present < 6 months prior to Screening., History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (< 6 months prior to Screening)., Active allergy requiring systemic treatment (with the exception of histamine H1 receptor blocker treatment) or active infections requiring systemic anti-infectious therapy., History of or clinical evidence of CNS primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, demonstrated no progression at least for 3 months before Screening, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before Screening – subjects with suspected brain metastases at Screening should undergo a CT/MRI of the brain prior to study entry., Systemic steroids at a daily dose of > 10 mg of prednisolone, > 2 mg of dexamethasone or equivalent, except non-systemic (inhaled, topical, nasal), for the last 28 days and ongoing., Major surgery within last 2 weeks prior to Screening (TURBT is not considered major surgery)., Known/expected hypersensitivity against visugromab (CTL-002) and/or anti-PD-1 agents or their ingredients or previously had a severe hypersensitivity (= Grade 3) reaction to treatment with monoclonal antibodies (including pembrolizumab, nivolumab etc.) and/or any of their excipients., Has received prior radiotherapy on the bladder tumor., Evidence for active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, tuberculosis, or severe acute respiratory syndrome coronavirus 2 as per adequate testing performed., Dementia or altered mental status that would prohibit informed consent, Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory abnormality giving reasonable suspicion of a disease or condition that in the opinion of the Investigator would contraindicate the use of an investigational drug or participation in a clinical study., Receipt of any organ transplantation, including hematopoietic cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant)., Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS., Vaccine administration within 4 weeks of investigational drug administration (exception: coronavirus disease 2019 [COVID-19] vaccination). Vaccination with live vaccines while on study is prohibited. Administration of inactivated vaccines like inactivated influenza vaccines or RNAvaccines is allowed, including COVID-19, Known active drug or alcohol abuse., Has received a partial cystectomy., Primary refusal to undergo RC., Has received any prior systemic anti-cancer therapy including investigational agents and immunotherapy., Has a known additional malignanc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method