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There are additional TRK inhibitors in clinical development, either multikinase inhibitors with anti-TRK activity or drugs that are specifically TRK-directed. Most of these include drugs with multiple potential targets and not all trials require patients to have tumours with NTRK gene fusion. Results from these clinical trials of these agents have not yet been reported (as of 6 June 2019).

Table 17: Additional TRK Inhibitors in Clinical Development

Drug

Company

Molecular target

Phase

Tumour type

Trial identifier

Cabozantinib

Exelixis

Multikinase
inhibitor (c-MET, VEGFR2, AXL and RET), TRKA, TRKB

2

NSCLC with NTRK fusion

NCT01639508

Merestinib

Eli Lilly

Multikinase inhibitor, including TRKA, TRKB, TRKC

2

Biliary tract cancer, NSCLC, solid tumours with NTRK
rearrangements, AML (phase 1), bone metastases (phase 1)

NCT02711553
NCT02920996
NCT03125239
NCT03292536

Sitravatinib (MGCD516) [1, 2]

Mirati Therapeutics

Multikinase inhibitor, including Trk family

1/2

NSCLC, head and neck cancer, liposarcoma, prostate
cancer, urothelial carcinoma

NCT02219711
NCT02954991
NCT02978859
NCT03015740
NCT03575598
NCT03606174

DS-6051b [3]

Daiichi Sankyo

ROS1 and TRKA, TRKB, TRKC

1

Phase 1 expansion cohorts: NSCLC, CRC, or other
solid tumours with ROS1, NTRK1, NTRK2, or NTRK3
rearrangement.
PR obtained in a patient with NTRK
fusion thyroid cancer

NCT02279433
NCT02675491

These data are current as of 6 June 2019 ( clinicaltrials.gov)

AML, acute myeloid leukaemia; CRC, colorectal cancer; NSCLC, non-small cell lung cancer; PR, partial response; RCC, renal cell carcinoma; ROS1, ROS proto-oncogene 1; TRKA, tropomyosin receptor kinase A; TRKB, tropomyosin receptor kinase B; TRKC, tropomyosin receptor kinase C.

References

  1. Leal TA, Horn L, Velastegui K et al. PS02.08 Evidence of Clinical Activity of Sitravatinib in Combination with Nivolumab in NSCLC Patients Progressing on Prior Checkpoint Inhibitor Therapy. Journal of Thoracic Oncology 2017; 12: S1567.
  2. Pant S, Spira AI, Cho BC et al. Evaluation of the spectrum selective RTK inhibitor sitravatinib in clear cell renal cell carcinoma (ccRCC) refractory to anti-angiogenic therapy (AAT). Journal of Clinical Oncology 2018; 36: 4568-4568.
  3. Papadopoulos KP, Gandhi L, Janne PA et al. First-in-human study of DS-6051b in patients (pts) with advanced solid tumors (AST) conducted in the US. Journal of Clinical Oncology 2018; 36: 2514-2514.

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