Lutetium Lu 177 Dotatate Shows Promise in Advanced Intracranial Meningioma

Data from a single-arm, phase 2 study (NCT03971461) shared during the 2025 Society for Neuro-Oncology Annual Meeting showed that the radiopharmaceutical Lutetium Lu 177 dotatate (Lutathera; 177Lu-Dotatate) was generally safe and tolerable in patients with advanced intracranial meningioma, with a 6-month progression-free survival (PFS) rate that surpassed historical benchmarks.1

177Lu-Dotatate led to a 6-month PFS rate of 69%, which met the trial’s primary end point. When broken down by World Health Organization (WHO) grade, 71% of those with grade 1 tumors were progression free at the 6-month time point, as were 68% of those with grade 2/3 tumors. These data were noted to compare favorably with historical controls, with 6-month PFS rates ranging from 29% to 43.6% for those in the grade 1 population and rates ranging from 26% to 38% for those in the grade 2/3 population.2,3

Moreover, the best radiographic response by MRI and RANO criteria was partial response for 5 patients and stable disease for 20 patients; 7 patients had progressive disease. The median PFS with 177Lu-Dotatate was 12.8 months (95% CI, 5.8-15.3), and the median overall survival (OS) was 25.3 months (95% CI, 18.6-not reached).

“The key take-home message from the phase 2 clinical study...was that we were able to show significantly improved PFS with 177Lu-Dotatate at 6 months over [that of] historical controls,” Sylvia C. Kurz, MD, PhD, told OncLive® in an exclusive interview.4 Kurz was the presenting author of the data and the interim section chief for Neuro-oncology and co-director of the Chenevert Brain Tumor Center at Yale Cancer Hospital.

What was the design of the phase 2 study evaluating 177Lu-Dotatate?

The single-arm, open-label study enrolled adult patients with histologically confirmed, progressive WHO grade 1 to 3 meningioma who were at least 18 years of age and had a Karnofsky performance status (KPS) of at least 60.1,5 Patients needed to have measurable disease and evidence of SSTR2 expression, either by immunohistochemistry in a prior specimen or by 68Ga-Dotatate uptake on PET-MRI.

Participants received 177Lu-Dotatate for a total of four doses at 7.4 GBq, 8 weeks apart. In addition to the primary end point being 6-month PFS rate, secondary end points included safety, 12-month OS rate, objective response rate (ORR), median OS, and median PFS.

“The study completed enrollment earlier [in 2025],” Kurz noted in the presentation.1 Among the 32 patients enrolled, the median age was 65.5 years (range, 41-78), and 69% of patients were aged 60 or older. Most patients were female (66%) and had a KPS ranging from 70% to 80%. Regarding histopathology, 22%, 75%, and 3% of patients had WHO grade 1, 2, or 3 disease, respectively. Tumor locations included convexity (50%), skull base (38%), or both (13%), and half of patients had multiple tumors.

Moreover, 44% of patients had 1 prior biopsy/resection, and 56% had more than 1 prior surgical intervention. Forty-four percent of patients had previously received 1 course of radiation, and 56% and received 1 or more prior courses of radiation. The majority of patients had not received previous medical therapy, but 13% had. “This is a heavily pretreated patient population; more than 50% of those patients had gone through more than 1 surgical resection and more than 1 course of radiation,” Kurz noted.

What was the toxicity profile of 177Lu-Dotatate in advanced intracranial meningiomas?

“The drug was, overall, fairly well tolerated,” Kurz added.

The most common adverse effects (AEs) reported with the radiopharmaceutical included alopecia (grade 1, 19%; grade 2, 0%; grade 3, 0%); cytopenias (100%; 100%; 47%) such as anemia (53%; 6%; 0%), leukopenia (63%; 31%; 13%), lymphopenia (47%; 53%; 25%), neutropenia (13%; 9%; 6%), and thrombocytopenia (50%; 3%; 3%); nausea or vomiting (13%; 0%; 0%); anorexia (9%; 3%; 0%); elevated transaminase levels (34%; 6%; 0%); electrolyte abnormalities (66%; 9%; 3%) like reduced bicarbonate levels (3%; 0%; 0%), hypo/hyperkalemia (19%; 0%; 3%), hypo/hypermagnesemia (6%; 3%; 0%), hyponatremia (16%; 3%; 0%), hypo/hyperphosphatemia (16%; 3%; 0%), and hypo/hypercalcemia (6%; 0%; 0%); hyperuricemia (grade 1, 6%); elevated amylase levels (9%; 6%; 3%); elevated lactate dehydrogenase levels (13%; 0%; 0%); elevated creatinine levels (13%; 0%; 0%); diarrhea (3%; 0%; 0%); cardiac arrhythmic event (6%; 0%; 3%); and fatigue (31%; 3%; 0%).

“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,” Kurz said.

What’s next for 177Lu-Dotatate?

Kurz noted that because investigators were “encouraged by these results,” the study informed the development of the phase 2 MOMENTUM-1 trial (NCT06955169), “which is a national multicenter study that has activated this month and will enroll patients at 50 sites across the United States.”

The open-label, multicenter, phase 2 study will randomly assign patients with progressive WHO grade 1 to 3 intracranial meningioma in a 2:1 fashion to receive 177Lu-Dotatate or investigator’s choice of standard-of-care treatment, which could include bevacizumab (Avastin), everolimus (Afinitor), hydroxyurea (Hydrea; Hydroxycarbamide), or sunitinib (Sutent).6 “At time of progression, those patients who received SOC treatments will be allowed to cross over in the investigational treatment arm,” Kurz noted.1

PFS will serve as the trial’s primary end point, and secondary end points will include 6-month PFS rate, 12-month OS rate, OS, PFS after crossover, disease control rate, ORR, and safety.6

References

1. Kurz SC, Zan E, Peereboom D, et al. Results of a single-arm, open-label, multicenter phase 2 study of the radiopharmaceutical [177Lu]Lu-DOTA-TATE in adults with advanced intracranial meningioma. Presented at: 2025 SNO Annual Meeting; November 19-23, 2025; Honolulu, Hawaii. Abstract CTNI-41.
2. Kotecha R, Akdemir EY, Kutuk T, et al. Benchmarking the efficacy of salvage systemic therapies for recurrent meningioma: A RANO group systematic review and meta-analysis to guide clinical trial design. Neuro Oncol. 2025;27(7):1670-1685. doi:10.1093/neuonc/noaf009
3. Kaley T, Barani I, Chamberlain M, et al. Historical benchmarks for medical therapy trials in surgery- and radiation-refractory meningioma: a RANO review. Neuro Oncol. 2014;16(6):829-840. doi:10.1093/neuonc/not330
4. Kurz SC. Dr Kurz on the efficacy and safety of Lutetium Lu 177 dotatate in advanced intracranial meningioma. OncLive.com. November 22, 2025. Accessed November 23, 2025. https://www.onclive.com/view/dr-kurz-on-the-efficacy-and-safety-of-lutetium-lu-177-dotatate-in-advanced-intracranial-meningioma
5. Phase II study of 177Lu-DOTATATE radionuclide in adults with progressive or high-risk meningioma. ClinicalTrials.gov. Updated April 22, 2025. Accessed November 23, 2025. https://clinicaltrials.gov/study/NCT03971461
6. Comparing the radiopharmaceutical drug, [177Lu]Lu-DOTATATE, to standard of care treatment for patients with meningioma that has come back after prior treatment (MOMENTUM-1). ClinicalTrials.gov. Updated November 13, 2025. Accessed November 23, 2025. https://clinicaltrials.gov/study/NCT06955169