Lutetium Lu 177 Dotatate Demonstrates Significant Efficacy in Advanced Intracranial Meningioma Phase 2 Trial
核心洞察
A phase 2 single-arm study of lutetium Lu 177 dotatate in 32 patients with advanced intracranial meningioma achieved a 6-month progression-free survival rate of 69%, significantly surpassing historical controls.
The radiopharmaceutical showed consistent efficacy across tumor grades, with 71% of grade 1 patients and 68% of grade 2/3 patients remaining progression-free at 6 months.
Treatment was generally well tolerated with manageable toxicities, primarily bone marrow suppression and electrolyte abnormalities, leading to advancement into the randomized phase 2 MOMENTUM-1 trial.
A phase 2 clinical trial evaluating lutetium Lu 177 dotatate (Lutathera) in patients with advanced intracranial meningioma has demonstrated significant efficacy, achieving a 6-month progression-free survival (PFS) rate of 69% that substantially exceeded historical benchmarks. The results, presented at the 2025 Society of Neuro-Oncology Annual Meeting, support the radiopharmaceutical's advancement into a larger randomized trial.
Study Design and Patient Population
The single-arm, open-label phase 2 study (NCT03971461) enrolled 32 adult patients with histologically confirmed, progressive WHO grade 1 to 3 meningioma. Participants were required to have a Karnofsky performance status of at least 60, measurable disease, and evidence of SSTR2 (搜索) expression demonstrated either by immunohistochemistry or 68Ga-Dotatate uptake on PET-MRI.
The patient population represented a heavily pretreated cohort, with a median age of 65.5 years and 69% of patients aged 60 or older. Most patients were female (66%), and tumor locations included convexity (50%), skull base (38%), or both (13%). Notably, 56% of patients had undergone more than one prior surgical intervention, and 56% had received multiple courses of radiation therapy.
Efficacy Results Exceed Historical Controls
Patients received lutetium Lu 177 dotatate at 7.4 GBq administered every 8 weeks for a total of four doses. The primary endpoint of 6-month PFS rate was met, with 69% of patients remaining progression-free at 6 months. When analyzed by WHO grade, the results showed consistent efficacy: 71% of patients with grade 1 tumors (n=7) and 68% of those with grade 2 tumors (n=25) achieved 6-month PFS.
"The key take-home message from the phase 2 clinical study was that we were able to show significantly improved PFS with lutetium Lu 177 dotatate at 6 months over [that of] historical controls," said Sylvia C. Kurz, MD, PhD, interim section chief for Neuro-oncology and co-director of the Chenevert Brain Tumor Center at Yale Cancer Hospital.
These results compare favorably to historical controls, which showed 6-month PFS rates ranging from 29% to 43.6% for grade 1 populations and 26% to 38% for grade 2/3 populations. The median PFS with lutetium Lu 177 dotatate was 12.8 months (95% CI, 5.8-15.3), and median overall survival was 25.3 months (95% CI, 18.6-not reached).
Response Rates and Safety Profile
Best radiographic response by MRI and RANO criteria included partial responses in 16% of patients (5 patients) and stable disease in 20% (20 patients), while 7 patients experienced progressive disease. The treatment was generally well tolerated, with the most common adverse events being bone marrow suppression and electrolyte abnormalities.
Cytopenias occurred in 100% of patients, with specific manifestations including anemia (53% grade 1, 6% grade 2), leukopenia (63% grade 1, 31% grade 2, 13% grade 3), and lymphopenia (47% grade 1, 53% grade 2, 25% grade 3). Electrolyte abnormalities affected 66% of patients at grade 1, 9% at grade 2, and 3% at grade 3. Other notable adverse events included alopecia (19% grade 1), elevated transaminase levels (34% grade 1), and fatigue (31% grade 1).
"The drug was, overall, fairly well tolerated," Kurz noted. "The main AEs that we saw were bone marrow suppression with cytopenias and electrolyte derangements, but there was 1 patient who discontinued treatment because of grade 4 cytopenia."
Advancement to Randomized Phase 2 Trial
Based on these encouraging results, lutetium Lu 177 dotatate is being evaluated in the phase 2 MOMENTUM-1 trial (NCT06955169), which activated in late 2025. This open-label, multicenter study will enroll patients with progressive WHO grade 1 to 3 intracranial meningioma at 50 sites across the United States.
The MOMENTUM-1 trial will randomly assign patients 2:1 to receive either lutetium Lu 177 dotatate or investigator's choice of standard-of-care therapy, which may include bevacizumab, everolimus, hydroxyurea, or sunitinib. Notably, patients assigned to standard-of-care treatment will be allowed to cross over to the investigational arm upon disease progression.
The primary endpoint will be PFS, with secondary endpoints including 6-month PFS rate, 12-month overall survival rate, overall survival, PFS after crossover, disease control rate, objective response rate, and safety. This randomized design will provide definitive evidence of lutetium Lu 177 dotatate's efficacy compared to current treatment options for this challenging patient population.