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Attend this session at the
2019 ASCO Annual Meeting!


Session: Pediatric Oncology II

Type: Oral Abstract Session

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

Location: S504

Identification of targetable molecular alterations in the NCI-COG Pediatric MATCH trial.

Sub-category:
Pediatric Solid Tumors

Category:
Pediatric Oncology

Meeting:
2019 ASCO Annual Meeting

Abstract No:
10011

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 10011)

Author(s): Donald Williams Parsons, Katherine A. Janeway, David Patton, Brent Coffey, Paul M. Williams, Stanley R. Hamilton, Anjan Purkayastha, Gregory J. Tsongalis, Mark Routbort, Julie M Gastier-Foster, Lauren Saguilig, Jin Piao, Todd Allen Alonzo, Stacey L. Berg, Elizabeth Fox, Peter C. Adamson, Margaret M. Mooney, Naoko Takebe, James V. Tricoli, Nita Seibel, NCI-COG Pediatric MATCH Team; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX; Dana-Farber Cancer Institute, Boston, MA; National Cancer Institute/Center for Biomedical Informatics & Information Technology, Rockville, MD; National Cancer Institute, Bethesda, MD; Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD; The University of Texas MD Anderson Cancer Center, Houston, TX; Frederick National Laboratory for Cancer Research, Rockville, MD; The Geisel School of Medicine at Dartmouth and Dartmouth Hitchcock Medical Center, Lebanon, NH; Nationwide Children's Hospital, Columbus, OH; Children's Oncology Group, Monrovia, CA; University of Southern California Children's Oncology Group, Arcadia, CA; Texas Childrens Cancer Center, Houston, TX; Children's Hospital of Philadelphia, Philadelphia, PA; National Cancer Institute, Rockville, MD; Developmental Therapeutics Clinic/Early Clinical Trials Development Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD

Abstract Disclosures

Abstract:

Background: The screening protocol for the NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial detects tumor alterations that are used to assign patients with treatment-refractory or recurrent cancers to phase 2 treatment arms of molecularly-targeted therapies. Methods: Patients age 1 to 21 years old with treatment-refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders treated at U.S. based COG sites are eligible. DNA and RNA extracted from FFPE tumor samples are sequenced using an Oncomine cancer gene panel for detection of mutations, amplifications, and fusions. Loss of SMARCB1, SMARCA4, and PTEN expression is detected by immunohistochemistry. Lists of actionable mutations (aMOIs) based upon available clinical and pre-clinical data are used a priori to determine eligibility for treatment arms. Results: Between 7/24/17 and 12/31/18, 422 patients with a median age of 13 years (range 1-21) were enrolled from 93 COG sites. Solid tumors comprised 71% (n = 300) of diagnoses, CNS tumors 24% (n = 101) and lymphomas/histiocytoses 5% (n = 21). A tumor sample was submitted for 390 patients, sequencing was attempted for 370 (95%), and results were confirmed for 357 (92%). Median turn-around time was 15 days. An aMOI for at least one of the 10 current treatment arms was identified in 112 patients (29%, 95% CI 24%-33%); 95 patients (24%, 95% CI 20%-29%) were assigned to a treatment arm with 39 patients (10%, 95% CI 7%-13%) enrolled to date. The aMOI rate was similar in patients less than 12 years of age (35%) compared to patients 12 years and older (25%). Actionable MAPK pathway alterations were found in 11% of patients (n = 41), most often HRAS/KRAS/NRAS mutations (n = 16), BRAF mutations or fusions (n = 14), or NF1 mutations (n = 11). Other genes with recurrent aMOIs included SMARCB1 (n = 14), ALK (n = 8), CDK4 (n = 8), PIK3CA (n = 7), PTEN (n = 7), FGFR1 (n = 5), and BRCA1/BRCA2 (n = 5). Conclusions: Approximately one-quarter of patients with tumor submitted for Pediatric MATCH screening have been assigned to an investigational therapy, facilitating the evaluation of molecularly-targeted agents in biomarker-positive pediatric cohorts through a collaborative nationwide study. Clinical trial information: NCT03155620

 
Other Abstracts in this Sub-Category:

 

1. Randomized phase 2 trial of the combination of vincristine and irinotecan with or without temozolomide, in children and adults with refractory or relapsed rhabdomyosarcoma (RMS).

Meeting: 2019 ASCO Annual Meeting Abstract No: 10000 First Author: Anne Sophie Defachelles
Category: Pediatric Oncology - Pediatric Solid Tumors

 

2. Temozolomide versus irinotecan-temozolomide for children with relapsed and refractory high risk neuroblastoma (RR-HRNB): Results of the BEACON-Neuroblastoma randomized phase 2 trial—A European Innovative Therapies for Children with Cancer (ITCC) - International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 10001 First Author: Lucas Moreno
Category: Pediatric Oncology - Pediatric Solid Tumors

 

3. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors.

Meeting: 2019 ASCO Annual Meeting Abstract No: 10009 First Author: Giles W. Robinson
Category: Pediatric Oncology - Pediatric Solid Tumors

 

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