(P 417) EFFICACY AND SAFETY OF LAROTRECTINIB (LARO) IN PATIENTS (PTS) WITH TRK FUSION SARCOMAS

Author(s)

Noah Federman, MD (he/him/his)

Clinical Professor, Pediatrics and Orthopaedic Surgery
University of California, Los Angeles
Los Angeles, California, United States

Co-Author(s)

Cv

Cornelis M. van Tilburg, MD, PhD

Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Research Center (DKFZ)
Heidelberg, Baden-Wurttemberg, Germany
Daniel Orbach, MD, PhD (he/him/his)

Deputy Director
SIREDO Oncology Center (Care, Innovation and Research for Children and AYA With Cancer), Institut Curie
Paris, Ile-de-France, France
CQ

Changsong Qi, MD, PhD

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute
Beijing, Beijing, China (People's Republic)
SD

Steven G. DuBois, MD, MS (he/him/his)

Associate Professor
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Boston, Massachusetts, United States
LM

Leo Mascarenhas, MD, MS

Cedars-Sinai Medical Center
Los Angeles, California, United States
MD

Miranda P. Dierselhuis, MD, PhD

Prinses Máxima Centrum
Utrecht, Utrecht, Netherlands
Catherine M. Albert, MD (she/her/hers)

Dr
Seattle Children's Hospital, University of Washington, Fred Hutchinson Cancer Center
Seattle, Washington, United States
CB

Claudia Blattmann, MD

Olgahospital
Stuttgart, Baden-Wurttemberg, Germany
Birgit Geoerger, MD, PhD

Faculty
Gustave Roussy Cancer Center, Université Paris-Saclay, INSERM U1015
Villejuif, Ile-de-France, France
HT

Helen Toledano, MBChB (she/her/hers)

Head Pediatric Neurooncology Unit
Schneider Children's Medical Center, Petah Tikva, Israel
Petach Tikva, HaMerkaz, Israel
DB

Domnita-Ileana Burcoveanu, MD, MSc

Bayer HealthCare Pharmaceuticals, Inc.
Basel, Basel-Stadt, Switzerland
NN

Natascha Neu, MSc

Chrestos GmbH
Essen, Nordrhein-Westfalen, Germany
NB

Nicoletta Brega, MD

Bayer HealthCare Pharmaceuticals, Inc.
Basel, Basel-Stadt, Switzerland
Alexander Drilon, MD

medical oncologist
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College
New York, New York, United States
TL

Theodore W. Laetsch, MD

The Children’s Hospital of Philadelphia, University of Pennsylvania Philadelphia
Philadelphia, Pennsylvania, United States
Rui-Hua Xu, MD, PhD

Professor
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China (People's Republic)

Co-Author(s)

Esther De La Cuesta, MD, MBA

Pediatric Advisor/ Senior Clinical Development Leader, Oncology
Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA
Whippany, New Jersey, United States

Objective: Laro is a first-in-class, highly selective TRK inhibitor approved for tumor-agnostic use in pts with TRK fusion cancer. We report efficacy and safety of laro in pts with TRK fusion sarcomas.

Methods: Pts enrolled in 3 laro clinical trials (NCT02122913, NCT02576431 [NAVIGATE], NCT02637687 [SCOUT]) were included. Responses were independent review committee-assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Pts in SCOUT could pause laro in the absence of on-treatment progression (“wait-and-see”). Data cutoff was July 20, 2024.

Results: At cutoff, 129 pts (38 adult; 91 pediatric) were enrolled (49 [38%] infantile fibrosarcoma [IFS]; 72 [56%] non-IFS soft tissue sarcoma [STS]; 5 [4%] gastrointestinal stromal tumors [GIST]; 3 [2%] bone sarcoma). NTRK gene fusions were identified by next-generation sequencing (NGS) in 99 (77%) pts. In the metastatic/unresectable setting, 49 (38%) pts received no prior therapies; 39 (30%) received ≥2.
Overall response rate (ORR) was 78% (95% confidence interval [CI] 69–84); 58 (45%) pts had complete response (CR; including 15 pathological CR [pCR]), 42 (33%) had partial response (PR), 16 (12%) had stable disease (SD), and 10 (8%) had progressive disease. Response could not be assessed in 3 pts. Highest ORR was in pts with IFS (94% [95% CI 83–99]; 63% had CR/pCR). Other efficacy outcomes are reported in the Table. At cutoff, 50 pts (39%) remained on treatment.
Of 93 pts enrolled in SCOUT, 51 (20 non-IFS STS; 31 IFS) entered a first “wait-and-see” period of median duration 33 (range 1–72) months. Of these, 16 (31%) restarted treatment; 11 (69%) had an investigator-assessed response (6 CR, 5 PR), 4 had SD, and 1 could not be assessed. Twelve (24%) pts exited the period and were alive at cutoff. Grade 3/4 treatment-related adverse events occurred in 33 (26%) pts.

Conclusion: Laro shows durable long-term responses and manageable safety in pts with TRK fusion sarcomas. This supports the wider adoption of NGS panels including NTRK gene fusions.

Table. Response to treatment
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