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Attend this session at the
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).

Sub-category:
Central Nervous System Tumors

Category:
Central Nervous System Tumors

Meeting:
2019 ASCO Annual Meeting

Abstract No:
2021

Poster Board Number:
Poster Session (Board #210)

Citation:
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

Abstract:

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

 

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