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2019 ASCO Annual Meeting!

Session: Central Nervous System Tumors

Type: Poster Session

Time: Sunday June 2, 8:00 AM to 11:00 AM

Location: Hall A

Full enrollment results from an extended phase I, multicenter, open label study of marizomib (MRZ) with temozolomide (TMZ) and radiotherapy (RT) in newly diagnosed glioblastoma (GBM).

Central Nervous System Tumors

Central Nervous System Tumors

2019 ASCO Annual Meeting

Abstract No:

Poster Board Number:
Poster Session (Board #210)

J Clin Oncol 37, 2019 (suppl; abstr 2021)

Author(s): Warren P. Mason, Santosh Kesari, Roger Stupp, Dawit Gebremichael Aregawi, David Eric Piccioni, Patrick Roth, Annick Desjardins, Steven D. Reich, Marie-Laure Casadebaig, Ileana Elias, Benjamin Winograd, Nancy Levin, Daniela Annenelie Bota; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; John Wayne Cancer Institute, Santa Monica, CA; Northwestern University, Chicago, IL; Penn State Hershey Medical Center, Hershey, PA; University of California, San Diego, CA; University Hospital Zurich, Zurich, Switzerland; Duke University Medical Center, Durham, NC; Triphase Accelerator, San Diego, CA; Celgene International, Boudry, Switzerland; Celgene Corporation, Summit, NJ; University of California Irvine, Irvine, CA

Abstract Disclosures


Background: Proteasome inhibition sensitizes glioma cells to TMZ and RT, providing a novel therapeutic strategy for GBM. MRZ, an irreversible, brain-penetrant, pan-proteasome inhibitor with anti-glioma activity was combined with standard TMZ/RT → TMZ in newly diagnosed GBM (NCT02903069), to determine the recommended dose (RD). The primary endpoint of this expanded phase 1 trial was toxicity, with secondary endpoint of OS. Methods: Patients were enrolled in separate cohorts (TMZ/RT+MRZ→TMZ+MRZ, N=15; TMZ/RT→TMZ+MRZ, N=18) in dose-escalation (3+3 design), followed by dose-expansion (N=20) with TMZ/RT+MRZ at RD → TMZ+MRZ at RD. A separate cohort received TMZ/RT→TMZ+MRZ at RD with Tumor Treating Fields (Optune, N=13). MRZ was infused IV (10 min at 0.55, 0.7, 0.8, and 1.0 mg/m2) on Days 1, 8, 15, 29, 36 (42-day TMZ/RT+MRZ cycle) and Days 1, 8, 15 (28-day TMZ+MRZ cycle). Results: 66 patients treated; median age 58 years, 68% male, 50% receiving corticosteroid at baseline, 52% unmethylated MGMT. Dose-limiting toxicities (DLTs) in dose-escalation cohorts: 1 (fatigue) at 0.7 mg/m2 MRZ, 5 (ataxia/diarrhea; ataxia/confusion; myocardial infarction, delirium/ataxia; ataxia/fatigue) in 1.0 mg/m2 cohorts. MRZ demonstrated a steep dose-response with treatment-emergent adverse events (TEAEs)/DLTs predominately CNS AEs (Grade ≥3 TEAEs in 12 of 12 patients at 1.0 mg/m2 vs 22 of 41 patients at ≤0.8 mg/m2); the RD for MRZ was determined to be 0.8 mg/m2. Most common TEAEs (all grades): fatigue, nausea (both 70%), hallucination (54%), vomiting (53%), headache (47%), confusional state (33%), ataxia, constipation, muscular weakness (all 29%). Conclusions: CNS TEAEs were short-lasting, reversible and ameliorated by early dose reductions (29% patients dose-reduced), allowing patients to remain on treatment. For patients receiving MRZ with TMZ/RT→TMZ (N=35), the median OS was 14.8 months (17 deaths, median follow-up 14.3 months), and 7 patients remain active (Cycles 11-23). The MRZ RD + TMZ/Optune combination was tolerated, with 4 of 13 patients treated on this arm remaining active. An international Phase 3 trial (EORTC 1709-BTG/CCTG CE.8, NCT03345095) is ongoing. Clinical trial information: NCT02903069

Other Abstracts in this Sub-Category:


1. Second interim and first molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2000 First Author: Martin J. Van Den Bent
Category: Central Nervous System Tumors


2. Randomized phase IIb clinical trial of continuation or non-continuation with six cycles of temozolomide after the first six cycles of standard first-line treatment in patients with glioblastoma: A Spanish research group in neuro-oncology (GEINO) trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2001 First Author: Carmen Balana
Category: Central Nervous System Tumors


3. Updated predictive analysis of the WHO-defined molecular subgroups of low-grade gliomas within the high-risk treatment arms of NRG Oncology/RTOG 9802.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2002 First Author: Erica Hlavin Bell
Category: Central Nervous System Tumors