A Clinical Trial Testing the Safety of the Investigational Drug Pumitamig (BNT327) and How Well it Works in Patients With Recurrent Glioblastoma

This multi-site Phase II study will enroll adults with histologically confirmed diagnosis of World Health Organization (WHO) Grade IV glioblastoma (GBM), isocitrate dehydrogenase (IDH)-wildtype consistent with WHO central nervous system (CNS) 2021 criteria who have received prior first-line treatment including with at least radiotherapy and temozolomide, with a Karnofsky performance status (KPS) ≥60, adequate organ function, and at least one measurable lesion according to the response assessment in neuro-oncology (RANO) 2.0 criteria.

Key Inclusion Criteria: * Adults, aged 18 to 75 years inclusive at the time of giving informed consent. Local laws will be followed in countries where adulthood is defined as older than 18 years. * Have a histologically confirmed diagnosis of WHO Grade IV GBM, IDH-wildtype consistent with WHO CNS 2021 criteria. * Have recurrent supratentorial GBM who have received prior treatment with at least radiotherapy and temozolomide. Exception: For participants who discontinued temozolomide or switched to an alternative treatment prior to disease recurrence due to temozolomide intolerance, an interval of ≥6 months between the completion of radiotherapy and first disease recurrence is acceptable. * Have first recurrence documented by magnetic resonance imaging (MRI), with an interval of at least 12 weeks after the end of prior radiotherapy unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field. * Have been clinically evaluated as having relapsed or progressed disease with at least one measurable lesion as the targeted lesion based on RANO 2.0 criteria. * Have KPS ≥60. * Can swallow the medication and maintain oral administration. * Have a baseline brain MRI, not more than 14 days before starting the study treatment. * Have a stable dose of steroids ≥7 days before the contrast-enhanced scan. * Have adequate organ function, as defined in the protocol. Key Exclusion Criteria: * Have received any of the following therapies or drugs before study enrollment: * Any anticancer therapies, including systemic, palliative, biologic, immunostimulatory, or immunosuppressive treatment within 4 weeks (or five half-lives, whichever is longer) before starting the study treatment. For bevacizumab, the washout period is 4 weeks before the first dose of study treatment. * Programmed death-1 / programmed death-ligand 1/vascular endothelial growth factor bispecific antibodies, cluster of differentiation 137 agonists or other immune checkpoint blockade therapies including monotherapy with either category or combinations thereof. * Systemic corticosteroids (at a dosage greater than 2 mg/day of dexamethasone or an equivalent dose of other corticosteroids) within 7 days before starting the study treatment. * Vaccinations with live attenuated vaccine(s) within 4 weeks before starting the study treatment. * Broad-spectrum intravenous antibiotics therapy within 2 weeks before starting the study treatment. * Any non-study investigational medicinal product within five half-lives of the first dose or within 4 weeks, whichever is longer, before starting the study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study. * Antiplatelet drugs, such as aspirin (\>325 mg/day), clopidogrel (\>75 mg/day), dipyridamole, ticlopidine or cilostazol, etc., within 10 days before starting the study treatment to avoid inclusion of participants who have used platelet aggregation inhibitors before the study. * Have had more than one recurrence of GBM. * Are allergic to dacarbazine and temozolomide. * Have known leptomeningeal disease, extracranial disease, or multicentric disease. * Have been diagnosed with secondary GBM (i.e., glioblastomas that progress from low grade diffuse astrocytoma or anaplastic astrocytoma). * Have previously received radiotherapy with anything other than standard radiotherapy (i.e., focally directed radiation). * Have received prior interstitial brachytherapy, interstitial thermal therapy, implanted chemotherapy, or therapeutics delivered by local injection or convection-enhanced drug delivery. Participants who had prior treatment with Gliadel® wafers and who had concurrent use of devices such as Tumor Treating Fields are excluded. * Have uncontrolled hypertension or poorly controlled diabetic conditions as specified in the protocol before study enrollment. * Are unable (due to existent medical condition, e.g., pacemaker or implantable cardioverter defibrillator device) or unwilling to have a head contrast-enhanced MRI. * Have undergone major surgery, open biopsy, or significant traumatic injury within 28 days before starting the study treatment, or a planned/anticipated need for major surgery during the study treatment period. Placement of vascular infusion devices is allowed. Note: If participant has had major surgery, they must have recovered adequately from the toxicity and/or complications from the treatment prior to the initiation of study treatment. * Have received allogeneic hematopoietic stem cell transplantation or organ transplantation. * Have had other malignant tumors within 5 years before starting the study treatment. Exception: those who have been cured with local treatment (such as basal cell or squamous-cell carcinoma of the skin, superficial or noninvasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary carcinoma of thyroid and early-stage prostate cancer). * Have any of the following heart conditions within 6 months before starting the study treatment: * Myocardial infarction, unstable angina, acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, cerebrovascular accident or other Grade 3 and above cardiovascular events. * New York Heart Association functional classification ≥II heart failure or left ventricular ejection fraction \