Abstracts CTIM-19. RANDOMIZED PHASE II OPEN-LABEL STUDY OF NIVOLUMAB PLUS STANDARD-DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW-DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM): FINAL REPORT Manmeet Ahluwalia1, Atulya Khosla1, yasmeen Rauf2, David Peereboom3, Patrick Y. Wen4, and David A. Reardon5; 1Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA, 2University of North Carolina, North Carolina, USA, 3Cleveland Clinic - Richard E. Jacobs Health Center, Cleveland, OH, USA, 4Dana-Farber Cancer Institute, Boston, MA, USA, 5Dana-Farber Cancer Insitute, Boston, MA, USA BACKGROUND: Anti-PD1 therapy alone in rGBM is of limited efficacy seen in three randomized trials. VEGF is upregulated proangiogenic growthfactor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF is promising approach. METHODS: 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performancestatus, and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: 90 patients (Median age 60.6 years, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall survival was similar between arm A and arm B (1 year: 41.1 vs 37.7%, p = 0.14), while OS was better for arm A in age > 60 compared to arm B (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P = 0.046). OS was not statistically different in the two arms for patients with age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P = 0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS: Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared bevacizumab monotherapy. Nivolumab with standard bevacizumab benefits patients older than 60 years old. Biomarkers of response data will be presented. CTIM-20. PROSPECTIVE RANDOMIZED PHASE II PLACEBOCONTROLLED TRIAL OF SURVAXM PLUS ADJUVANT TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA (SURVIVE) Manmeet Ahluwalia1, michael J Ciesielski2, Ajay Abad3, David A. Reardon4, Robert Aiken5, marissa barbaro6, kaylyn sinicrope7, David Peereboom8, yazmin odia1, andrew brenner9, vyshak venur10, Ahmed belal2, Jingxin qiu2, Atulya Khosla1, cathy schilero11, danielle casucci12, laszlo mechtler2, and Robert Fenstermaker3; 1Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA, 2Roswell Park, Buffalo, USA, 3Roswell Park, Buffalo, NY, USA, 4Dana-Farber Cancer Insitute, Boston, MA, USA, 5Rutgers, new jersey, NJ, USA, 6NYU, new york, USA, 7harvard, boston, USA, 8Cleveland Clinic - Richard E. Jacobs Health Center, Cleveland, OH, USA, 9UT Health, texas, USA, 10UW, seattle, USA, 11Cleveland Clinic, Cleveland, USA, 12Mimivax, Buffalo, USA BACKGROUND: Newly diagnosed glioblastoma (nGBM) has a dismal prognosis with survival of 15-18 months. Tumor associated “survivin” protein is expressed in >95% of nGBM and is targetable with the use of vii64 NEURO - O N C O L O G Y • Nov e m be r 2 0 2 2 SurVaxM, shown to be effective at generating cytotoxic T lymphocytes. METHODS: nGBM patients are being enrolled in this randomized placebocontrolled trial phase II study. Eligibility Criteria includes age ≥ 18, KPS ≥ 70, IHC confirmed survivin-expression, and residual contrast enhancement of ≤1 cm3 by MRI, within 72 hours of surgical resection. Patients are randomized 3:2 into two arms A:B to treatment with SurVaxM in emulsion with Montanide plus sargramostim (local injection) and standard-of-care TMZ (Arm A), or placebo (saline in emulsion with Montanide) plus saline (local injection) and standard-of-care TMZ (Arm B). There are three active treatment phases in the study with vaccine priming (VP) phase; adjuvant TMZ phase; and Vaccine Maintenance (VM) phase. A total of four (4) priming doses of SurVaxM in Montanide plus sargramostim (“SurVaxM/ sargramostim”) or placebo in Montanide/saline (“Placebo/Placebo”) will be administered every two weeks ( ± 3 days) during the priming phase, with subsequent dosing every 8 weeks ( ± 1 week) during the vaccine maintenance phase. After priming doses, SurVaxM/sargramostim or Placebo/Placebo will be administered every 8 weeks ( ± 1 week) until tumor progression or for a maximum of 24 months. The total sample size is of 265 patients, with 159 patients in the SurVaxM arm and 106 patients in the control arm. The primary objective is to determine the overall survival (OS), and the secondary objectives include progression-free survival (PFS), OS at pre-specified time points (OS-15, OS-18 and OS-24), PFS at pre-specified time points (PFS-3, PFS-6 and PFS-12) and evaluation of toxicities. Study duration is expected at 36 months, with enrollment ongoing at several centers and planned for total of 20 participating centers. CTIM-21. NRG-BN010: A SAFETY RUN-IN AND PHASE II STUDY EVALUATING THE COMBINATION OF TOCILIZUMAB, ATEZOLIZUMAB, AND FRACTIONATED STEREOTACTIC RADIOTHERAPY IN RECURRENT GLIOBLASTOMA – TRIAL IN PROGRESS Stephen Bagley1, Mei-Yin Polley2, Rupesh Kotecha3, Steven Brem4, Ranjini Tolakanahalli3, Fabio Iwamoto5, Mark Gilbert6, Minhee Won7, and Minesh Mehta8; 1Hospital of the University of Pennsylvania, Philadelphia, PA, USA, 2NRG Oncology, Chicago, IL, USA, 3Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA, 4Hospital of the University of Pennsylvania, Philadelphia, USA, 5Division of Neuro-Oncology, New York-Presbyterian/Columbia University Medical Center, New York, NY, USA, 6Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, 7NRG Oncology, Philadelphia, PA, USA, 8Baptist Health South Florida, Miami, FL, USA BACKGROUND: The glioblastoma (GBM) tumor microenvironment (TME) is characterized by a paucity of effector T cells and massive infiltration of immunosuppressive tumor-associated macrophages (TAMs). Inhibition of the interleukin-6 receptor (IL6R) has been demonstrated in preclinical models to repolarize TAMs toward an immunostimulatory phenotype, rendering GBM more susceptible to PD-1/PD-L1 inhibition. Additional preclinical data suggest that fractionated stereotactic radiotherapy (FSRT) can stimulate the release and presentation of tumor-specific antigens, acting as an in-situ vaccine and potentially converting a “cold” TME to a T cell-inflamed state. We designed a safety run-in and phase II study to evaluate the efficacy, safety, and impact on the TME of the combination of IL6R inhibition (tocilizumab), PD-L1 inhibition (atezolizumab), and FSRT in patients with recurrent GBM (rGBM). METHODS: NRG-BN010 (NCT04729959) is open to enrollment for adults with rGBM following prior radiotherapy and has 3 components: a safety run-in to determine the recommended phase II dose (RP2D) of the treatment regimen, a phase II single-arm nonsurgical cohort to assess efficacy of the treatment regimen at the RP2D, and a window-of-opportunity surgical cohort. Once the safety run-in (n=12, 3 + 3 design) has determined the RP2D, the phase II and surgical cohorts will open. Phase II patients (n=25, Simon 2-stage design, primary endpoint objective radiographic response) receive an initial pre-FSRT cycle of tocilizumab (plus atezolizumab if included in the RP2D). Within 3-7 days later, the patient receives FSRT (8 Gy x 3 fx), followed by resumption of systemic therapy. Surgical cohort patients (n=16, 1:1 randomization) receive a neoadjuvant cycle of atezolizumab with (n=8) vs. without (n=8) tocilizumab, then FSRT 3-7 days later, then surgical resection 7-14 days after FSRT. Post-operatively, all patients resume systemic therapy at the RP2D. Fresh tumor tissues will be subjected to deep immune profiling to understand the impact of tocilizumab on TAMs in the GBM TME. CTIM-22. THE COMBINATION OF LOMUSTINE AND THE IMMUNOCYTOKINE L19TNF IS A PROMISING TREATMENT FOR RECURRENT GLIOBLASTOMA Thomas Look1, Emanuele Puca2, Riccardo Stucchi2, Roberto De Luca2, Patrick Roth3, Dario Neri2, Michael Weller4, Teresa Hemmerle2, and Tobias Weiss5; 1Department of Neurology and Clinical Neuroscience Center, University Hospital and University of Zurich, Switzerland, Zurich, Switzerland, 2Philogen S.p.A.,, Siena, Italy, 3University Hospital Zurich, Zurich, Switzerland, 4Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland, 5Department of Neurology and Downloaded from https://academic.oup.com/neuro-oncology/article/24/Supplement_7/vii64/6826159 by guest on 16 November 2022 day and were ≥ 6 months from initial conventional radiation therapy were eligible. Cohort A (bevacizumab [BEV]-naïve) had ≤ 2 prior progressions while cohort B (BEV-refractory) allowed unlimited progressions but only one on prior BEV. Re-irradiation included 35 Gy over 10 fractions to residual enhancing (cohort A) as well as enhancing + non-enhancing (cohort B) disease. Pembrolizumab was administered at 200 mg every three weeks beginning within one week of re-irradiation start. BEV was administered at 15 mg/kg every three weeks for cohort B only. RESULTS: Sixty patients enrolled (n = 30 per cohort) with a median age of 61 years (range 20-76), 47% were female and 53% enrolled after 2 or more progressions. Grade 3 events deemed at least possibly related to study therapy in > one patient for cohort A included headache (n = 2) and for cohort B included elevated ALT (n = 2) and hypertension (n = 5). No grade 4 events occurred in more than single patients per cohort and no grade 5 events occurred. Median PFS and PFS-6 were 4.9 months (95% CI: 3.5, 5.6) and 26.0% (95% CI: 12.3%, 43.0%) for cohort A and 4.14 months (95% CI: 3.45, 5.42) and 16.9% (95% CI: 5.4, 33.7) for cohort B. Median survival for cohorts A and B were 11.5 months (95% CI: 9.6, 14.1) and 7.6 months (95% CI 5.5, 9.3), respectively. CONCLUSIONS: Re-irradiation with pembrolizumab was overall well tolerated and achieved comparable efficacy to historical salvage therapy established with lomustine.