A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent.

A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Radiotherapy With or Without Temozolomide and in Recurrent Glioblastoma as Single Agent

A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Standard of Care and in Recurrent Glioblastoma as a Single Agent

The study for each participant consists of a Screening period, a Treatment period and a 12-month Follow-up period.

During the screening period of up to 6 weeks before starting GBM treatment, each participant will be assessed for somatostatin receptor (SSTR) expression by [68Ga]Ga-DOTA-TATE imaging PET/scan.

Eligible participants with newly diagnosed glioblastoma will be assigned to Group 1 :

• Participants in Group 1 (concomitant radiotherapy + temozolomide and temozolomide maintenance) will receive treatment with [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days, up to 6 administrations. Radiotherapy and temozolomide will be administered 7 to 10 days after the first administration of [177Lu]Lu-DOTA-TATE. Temozolomide will be administered orally at a dose of 75 mg/m2/day during the concomitant period, concurrently with radiotherapy. Radiotherapy will be delivered at a dose of 2 Gray (Gy)/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks with a total dose of 60 Gy (without interruption). During the maintenance period, there is an intra-patient dose escalation in temozolomide treatment. The dosage of temozolomide is 150 mg/m2 in Cycle 1 of maintenance period, and then to 200 mg/m2 in Cycle 2 and beyond in the maintenance period, if 150 mg/m2 temozolomide treatment is well tolerated in Cycle 1.

Eligible participants with recurrent glioblastoma will be assigned to Group 3 and will receive [177Lu]Lu-DOTA-TATE as single agent treatment every 3 weeks +/- 2 days.

An infusion of sterile 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each [177Lu]Lu-DOTA-TATE dose for renal protection.

Key Inclusion Criteria:

Common Criteria:

• Participant is >= 18 years on the day of signing informed consent form
• Histologically confirmed glioblastoma
• Adequate bone marrow, organ function and electrolyte values

Newly diagnosed glioblastoma (Group 1):

• Presence of Gadolinium enhancing tumor in pre-surgery magnetic resonance imaging (MRI)
• Karnofsky Performance Score (KPS) >= 70 %

Recurrent glioblastoma (Group 3 dose Escalation only):

• Participant has experienced first or second recurrence of their glioblastoma, after standard or experimental therapy that includes prior EBRT

Recurrent glioblastoma (Group 3 dose escalation and expansion):

• Evidence of recurrent disease demonstrated by disease progression using modified Response Assessment in Neuro-Oncology (mRANO) criteria

• KPS >= 60 %

• [68Ga]Ga-DOTA-TATE uptake by positron emission tomography/computed tomography (PET/CT) or PET/MRI at the tumor region

• Presence of Gadolinium enhancement in the tumor region in MRI at the time of diagnosis of tumor recurrence

• A second surgery for glioblastoma is allowed provided that the following criteria are met:

  1. Residual and measurable disease post-surgery is not required but surgery must have confirmed the diagnosis of recurrence

  2. Surgery completed at least 2 weeks prior to study treatment initiation, with post-surgery recovery without any complications related to surgical procedure

     Recurrent glioblastoma (Group 3 Dose Expansion only):

• Patients experiencing first recurrence of their glioblastoma, after standard or experimental therapy that includes prior EBRT

Key Exclusion Criteria:

Common Criteria:

• Participant is receiving additional, concurrent, active therapy for glioblastoma outside of the trial
• Extensive leptomeningeal disease
• History of another active malignancy in the previous 3 years prior to study entry
• Prior administration of a radiopharmaceutical unless 10 or more effective half-lives have elapsed before injection of [68Ga]Ga-DOTA-TATE or [177Lu]Lu-DOTA-TATE

Newly diagnosed glioblastoma (Group 1):

• Any prior treatment for glioma of any grade

Recurrent glioblastoma (Group 3 dose escalation and expansion):

• Early disease progression prior to 3 months from the completion of radiotherapy
• Previous treatment with bevacizumab for the treatment of glioblastoma with therapeutic intent, or with bevacizumab as supportive therapy (e.g. edema reduction) within 60 days of initiation of study treatment

Recurrent glioblastoma (Group 3 dose escalation only):

• More than 2 prior lines for systemic therapy

Recurrent glioblastoma (Group 3 dose expansion only):

• More than 1 prior line for systemic therapy