A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma.
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Wen Patrick Y, Manzanera Andrea, Duault Caroline, Gonzalez-Kozlova Edgar, Lopez Lenika, Grossman Stuart A, Ye Xiaobu, Fisher Joy, Lee Ian, Walbert Tobias, Snyder James, Brem Steven, Desai Arati, Bagley Stephen J, Kakani Chandana, Strowd Roy, Tatter Stephen, Laxton Adrian, Lesser Glenn, Amankulor Nduka, Lieberman Frank, Drappatz Jan, Mantica Megan, Triggs Dan, Haymaker Cara, Wistuba Ignacio I, Al-Atrash Gheath, Mendoza Perez Julia, Futreal Andrew, Little Latasha D, Islam M D Habibul, Duose Dzifa, Jiang Peixin, Reuben Alexandre, Lawler Sean E, Pichavant Mina, Gentles Andrew, Bendall Sean, Kong Alex, Camacho Christine, Del Valle Diane, Kim-Schulze Seunghee, Gnjatic Sacha, Sharon Elad, Nowicki M Oskar, Peruzzi Pierpaolo, Lane Doug, Aguilar-Cordova Estuardo, Aguilar Laura K, Nichols Garrett, Dwyer Jessica, Tak Paul Peter, Maecker Holden, Barone Francesca, Chiocca E Antonio
Аннотация
METHODS: Forty-one patients with suspected newly diagnosed GBM by imaging were enrolled in this multi-institutional, open-label, phase 1b clinical trial before surgical resection. Frozen section confirmation of high-grade glioma was required for administration of CAN-2409. This was then followed with chemoradiation and adjuvant nivolumab. Tumor and blood were assayed for genetic and immune markers before and during treatment.
RESULTS: The regimen was well tolerated and generated measurable immune activation. Factors linked to survival were identified, such as baseline mutated gene pairs (eg, MED15/HRC), tumor immune cell composition, and changes in systemic cytokine, immune cells, and T-cell diversity. The most significant serial systemic immune changes were observed in a long-term survivor subset of patients with gross total resection (GTR)/methylated methylguanine methyltransferase (MGMT) promoter tumors. Median overall survival (mOS) in these patients was 30.6 months, while it was less for patients with unmethylated or subtotal resections.
CONCLUSIONS: These findings suggest the opportunity for patient stratification and the potential for more durable antitumor immune responses in future clinical trials of this multimodal standard of care and combined immunotherapy regimen. ClinicalTrials.gov identifier: NCT03576612.