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2019 ASCO Annual Meeting!


Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)

Type: Oral Abstract Session

Time: Monday June 3, 8:00 AM to 11:00 AM

Location: S406

Dabrafenib and trametinib in patients with tumors with BRAF V600E/K mutations: Results from the molecular analysis for therapy choice (MATCH) Arm H.

Sub-category:
Small Molecules

Category:
Developmental Therapeutics and Tumor Biology (Nonimmuno)

Meeting:
2019 ASCO Annual Meeting

Abstract No:
3002

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 3002)

Author(s): April K.S. Salama, Shuli Li, Erin Renee Macrae, Jong-In Park, Edith P. Mitchell, James A. Zwiebel, Helen X. Chen, Robert James Gray, Lisa McShane, Lawrence Rubinstein, David Patton, Paul M. Williams, Stanley R. Hamilton, Deborah Kay Armstrong, Barbara A. Conley, Carlos L. Arteaga, Lyndsay Harris, Peter J. O'Dwyer, Alice P. Chen, Keith Flaherty; Duke University, Durham, NC; E-A Biostatistical Center-Boston, Boston, MA; Columbus Oncology and Hematology Associates Inc, Columbus, OH; Medical College of Wisconsin, Milwaukee, WI; Thomas Jefferson Univ Hosp, Philadelphia, PA; Cancer Therapy Evaluation Program, Bethesda, MD; CTEP National Cancer Institute, Rockville, MD; Dana-Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA; Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; National Cancer Institute/Center for Biomedical Informatics & Information Technology, Rockville, MD; Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD; The University of Texas MD Anderson Cancer Center, Houston, TX; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX; Cancer Diagnosis Program, National Cancer Institute, Rockville, MD; University of Pennsylvania Abramson Cancer Center, Division of Medical Oncology, Philadelphia, PA; Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD; Dana-Farber Cancer Institute/Harvard Medical School and Massachusetts General Hospital, Boston, MA

Abstract Disclosures

Abstract:

Background: The NCI-MATCH precision medicine trial assigns patients (pts) with solid tumors, lymphomas, or multiple myeloma with progression on prior treatment to a targeted therapy based on genetic alterations identified in pre-treatment biopsies. Arm H (EAY131-H) evaluated the combination of the BRAF inhibitor (inh) dabrafenib (DAB), and the MEK inh, trametinib (TRM), in pts with BRAF V600E/K mutations. Methods: Pts with melanoma, thyroid, or colorectal cancer were excluded. Pts with NSCLC were excluded after the U.S. Food and Drug Administration (FDA) approved DAB/TRM for this indication. Pts received DAB 150 mg po BID and TRM 2 mg PO daily on 28 day cycles until disease progression or intolerable toxicity; restaging was performed every 2 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Results: A total of 35 pts were enrolled from 1/2016-2/2018; 2 were ineligible (CrCl below criteria; labs out of window). Over 17 distinct tumor histologies were represented. 58% of pts were female, median age was 63 (range 21-85), 94% were Caucasian, and 48% of pts had received at least 3 prior therapies (range 1- 8). The confirmed ORR was 33.3% (90% CI 19.9%, 49.1%), with a median duration of response (DoR) of 12 months (mon). Varied histologies had a DoR of > 12 mon: histiocytic sarcoma, cholangiocarcinoma and mixed adenoneuroendocrine carcinoma of unknown primary, among others. Median PFS was 9.4 mon; the 6 mon PFS rate was 70.6% (90% CI 58.2%-85.5%), and an additional 10 pts had a PFS > 5.5 mon. Median OS has not been reached. At the time of data cutoff (12/2018) 11 pts continue on treatment. Adverse events (AE) were comparable to previously reported profiles of DAB/TRM; no new AEs were identified. The most frequent grade 3 AEs were fatigue, neutropenia, hyponatremia, hypophosphatemia, and urinary tract infection; there was 1 grade 4 sepsis; no grade 5 AEs. Conclusions: In this pre-treated, mixed histology cohort, DAB and TRM showed promising activity outside of currently approved FDA indications warranting further investigations. Correlative analyses are planned. Clinical trial information: NCT02465060

 
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