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

Key Inclusion Criteria:

• Adults, aged 18-75 years inclusive at the time of giving informed consent. Locallaws will be followed if the age at consent is older.

• Have a histologically confirmed diagnosis of WHO Grade IV GBM, IDH-wildtypeconsistent with WHO CNS 2021 criteria.

• Have recurrent supratentorial GBM who have received prior treatment with at leastradiotherapy and temozolomide.

• Have first recurrence documented by magnetic resonance imaging (MRI), with aninterval of at least 12 weeks after the end of prior radiotherapy unless there iseither: i) histopathologic confirmation of recurrent tumor, or ii) new enhancementon MRI outside of the radiotherapy treatment field.

• Have been clinically evaluated as having relapsed or progressed disease with atleast 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 studytreatment.

• 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 fivehalf-lives, whichever is longer) before starting the study treatment.

• PD(L)-1/VEGF bispecific antibodies, cluster of differentiation (CD)137 agonistsor other immune checkpoint blockade therapies including monotherapy with eithercategory or combinations thereof.

• Systemic corticosteroids (at a dosage greater than 2 mg/day of dexamethasone oran equivalent dose of other corticosteroids) within 7 days before starting thestudy treatment.

• Vaccinations with live attenuated vaccine(s) within 4 weeks before starting thestudy treatment.

• Broad-spectrum intravenous antibiotics therapy within 2 weeks before startingthe study treatment.

• Any non-study investigational medicinal product within five half-lives of thefirst dose or within 4 weeks, whichever is longer, before starting the studytreatment in this study or ongoing participation in the active treatment phaseof 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 startingthe study treatment to avoid inclusion of participants who have used plateletaggregation 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 lowgrade 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 orconvection-enhanced drug delivery. Participants who had prior treatment withGliadel® wafers and who had concurrent use of devices such as Tumor Treating Fieldsare excluded.

• Have uncontrolled hypertension or poorly controlled diabetic conditions as specifiedin the protocol before study enrollment.

• Are unable (due to existent medical condition, e.g., pacemaker or implantablecardioverter defibrillator device) or unwilling to have a head contrast-enhancedMRI.

• Have undergone major surgery, open biopsy, or significant traumatic injury within 28days before starting the study treatment, or a planned/anticipated need for majorsurgery during the study treatment period. Placement of vascular infusion devices isallowed. Note: If participant has had major surgery, they must have recoveredadequately from the toxicity and/or complications from the treatment prior to theinitiation of study treatment.

• Have received allogeneic hematopoietic stem cell transplantation or organtransplantation.

• 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 orsquamous-cell carcinoma of the skin, superficial or noninvasive bladder cancer,carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, andpapillary carcinoma of thyroid and early-stage prostate cancer).

• Have any of the following heart conditions within 6 months before starting the studytreatment:

• Myocardial infarction, unstable angina, acute coronary syndrome, coronaryartery 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 leftventricular ejection fraction <50%.

• Ventricular arrhythmias requiring clinical intervention, second- tothird-degree atrioventricular block, or congenital long QT syndrome.Participants with stable treated cardiac arrythmia/atrial fibrillation areallowed.

• Mean QTcF >480 ms (the electrocardiogram can be repeated at the discretion ofthe investigator).

• Cardiac troponin I or T >2 × upper limit normal.

• Have serious or non-healing wounds, ulcers, or (incompletely healed) bone fracture.This includes history (within 6 months before starting the study treatment) or riskof abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, orintra-abdominal abscess or esophageal and gastric varices, or acute gastrointestinalbleeding. In addition, the participant must have undergone correction (orspontaneous healing) of the perforation/fistula and/or the underlying processcausing the fistula/perforation.

• Have significant risk of hemorrhage (in the opinion of the investigator) or evidenceof major coagulation disorders.

• Have uncontrolled pleural effusion, pericardial effusion, or ascites requiringrecurrent drainage procedures (once monthly or more frequently). However,participants who are clinically stable following treatment for these conditions (including therapeutic thoracentesis or paracentesis or with indwelling catheters,e.g., PleurX) are allowed.

• Have adverse events from prior antitumor therapy that have not returned to Grade 1 (graded by CTCAE v5.0 criteria) or below (unless the investigator determines thatcertain adverse events pose no safety risk to participants, such as hair loss orstable hypothyroidism under hormone replacement therapy).

• Active colitis, including infectious, radioactive, ischemic enteritis, within 4weeks before starting the study treatment.

• History of serious allergic diseases, history of serious allergy to drugs (includingunlisted investigational drug) or known allergy or intolerance to any ingredient ofthe study treatment.

• Uncontrolled seizures after best medical therapy or other neurological conditionsincluding clinically significant autoimmune neurological disorders which canincrease risk for adverse effects or confound assessment of study outcomes asdetermined by the investigator.

• Have superior vena cava syndrome or symptoms of spinal cord compression.

• Have active, or a history of, pneumonitis requiring treatment with steroids, or haveactive or a history of interstitial lung disease.

• Have a known history of tuberculosis that was not successfully treated.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.