A Study to Evaluate the Safety and Efficacy of the Tumor-targeting Human Antibody-cytokine Fusion Protein L19TNF Plus Lomustine in Patients With Glioblastoma at First Progression
Glioblastomas are the most common and most aggressive primary brain tumors in adults. The prognosis is poor despite multimodal therapy with surgery, radiotherapy and chemotherapy. Therefore, novel treatments are urgently needed. L19TNF is a fully human fusion protein consisting of human tumor necrosis factor (TNF)-α fused to the L19 antibody in scFv format, specific to the extra-domain B of fibronectin. TNF not only induces apoptosis or necrosis in certain target cells, but also exerts inflammation and immunity. L19TNF selectively delivers TNF to the tumor site to spare normal tissues from undesired toxicity. Preclinical experiments with L19TNF have demonstrated tumor growth retardation in various mouse tumor models including models of glioma.
• Male or female, age ≥18.
• Patients with histologically confirmed glioblastoma at unequivocal first recurrence or progression according to RANO criteria.
• MGMT promotor methylation status known
• IDH wildtype.
• Patients may have undergone surgery for recurrence.
• For operated patients: The histological report must document glioblastoma recurrence and a new MRI will need to be done at 3-5 weeks after surgery (directly before study treatment start). Study treatment will need to start minimum 4 weeks to maximum 6 weeks after surgery.
• Karnofsky Performance Status (KPS) ≥ 70%.
• Documented negative test for HIV-HBV-HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required. For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
• Female patients: female patients must be either documented not Women Of Childbearing Potential (WOCBP)\* or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to 6 months following the last study drug administration, highly effective contraception methods, as defined by the Recommendations for contraception and pregnancy testing in clinical trials issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner.
• Male patients: male subjects able to father children must agree to use two acceptable methods of contraception throughout the study (e.g. condom with spermicidal gel). Double-barrier contraception is required.
⁃ Personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
⁃ Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
‣ Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).