Journal article
ACTR-39. PAMIPARIB IN COMBINATION WITH RADIATION THERAPY (RT) AND/OR TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED OR RECURRENT/REFRACTORY (R/R) GLIOBLASTOMA (GBM); PHASE 1B/2 STUDY UPDATE
- Piotrowski, Anna Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Puduvalli, Vinay The Ohio State University, Columbus, OH, USA
- Wen, Patrick Dana-Farber Cancer Institute, Boston, MA, USA
- Campian, Jian Washington University School of Medicine, St. Louis, MO, USA
- Colman, Howard Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
- Pearlman, Michael Sarah Cannon Research Institute at Health One, Denver, CO, USA
- Butowski, Nicholas University of California San Francisco, San Francisco, CA, USA
- Battiste, James Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Glass, Jon Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
- Cloughesy, Timothy University of California Los Angeles, Los Angeles, CA, USA
- Schiff, David University of Virginia Health Systems Emily Couric Clinical Cancer Center, Charlottesville, VA, USA
- van den Bent, Martin Erasmus University Medical Center, Rotterdam, Netherlands
- Walbert, Tobias Henry Ford Health System, Detroit, MI, USA
- Ahluwalia, Manmeet Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
- Badruddoja, Michael Center for Neurosciences, Tucson, AZ, USA
- Kalra, Amandeep Sarah Cannon Cancer Institute at Menorah Medical Center, Overland Park, KS, USA
- Aregawi, Dawit Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
- Weller, Michael Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
- Ramakrishnan, Vanitha BeiGene USA, Inc., Emeryville, CA, USA
- Zhang, Kathy BeiGene USA, Inc., Emeryville, CA, USA
- Wood, Katie BeiGene USA, Inc., Emeryville, CA, USA
- Mellinghoff, Ingo Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Shih, Kent Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA
- 2019-11-11
Published in:
- Neuro-Oncology. - Oxford University Press (OUP). - 2019, vol. 21, no. Supplement_6, p. vi21-vi22
English
Abstract
Pamiparib, an investigational, selective PARP1/2 inhibitor that has demonstrated potent PARP trapping and ability to cross the blood-brain barrier, showed synergistic cytotoxicity with TMZ preclinically. We report updated safety and antitumor effects from a phase 1b/2 study of pamiparib + RT and/or TMZ in patients with newly diagnosed or R/R GBM (SNO 2018, ACTR-30). The dose-escalation/expansion study has 3 arms: Arm A, pamiparib (2, 4, or 6 weeks) + RT in newly diagnosed GBM patients with unmethylated MGMT promoter (unmethylated-GBM); Arm B, pamiparib (6 weeks) + RT and increasing TMZ dosed in weeks 1 and 5 of RT in newly diagnosed, unmethylated-GBM patients; and Arm C, pamiparib + increasing TMZ doses in methylated/unmethylated R/R-GBM patients. Arm A and B patients receive maintenance treatment post-RT rest period at the Arm C expansion dose/schedule. As of 10 April 2019, accrual was completed for Arms A and C dose-escalation (A: n=20; C: n=17) and continues in the dose expansion (A: n=28/40; C: n=28/30); accrual was completed in dose escalation for B (n=9). Recommended phase 2 doses were established for Arms A (pamiparib 60 mg BID×6 weeks + 6–7 weeks RT) and C (pamiparib 60 mg BID d1–28 + TMZ 60 mg d1–7/28-d cycle). One dose-limiting toxicity (grade 3 febrile neutropenia) was reported in Arm B. Treatment-related adverse events (≥10%) were (overall/grade 3 [no grade 4/5]): Arm A, nausea (23%/2%); B, decreased WBC count (11%/11%); C (none). Of patients with tumor assessment post-RT: Arm A (n=17), 1 had cPR, 1 uPR, and 9 SD (disease control rate, 64.7% [95% CI, 38.3–85.8]); C (n=26), 1 had cPR (sustained 12 cycles), 1 uPR, and 5 SD (objective response rate, 7.7% [95% CI, 0.9–25.1]). Pamiparib 60 mg BID + RT/TMZ was generally well tolerated in patients with newly diagnosed or R/R GBM. Clinical trial ID: NCT03150862
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1093/neuonc/noz175.081
- ISSN 1522-8517
- Persistent URL
- https://sonar.ch/global/documents/41760
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