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Cited by 113Lung Cancer Treatments and MutationsCancer Mechanisms and TherapySarcoma Diagnosis and Treatment

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

U.S. Phase I First-in-human Study of Taletrectinib (DS-6051b/AB-106), a ROS1/TRK Inhibitor, in Patients with Advanced Solid Tumors

Papadopoulos, Kyriakos P., Borazanci, Erkut, Shaw, Alice T., Katayama, Ryohei, Shimizu, Yuki, Zhu, Viola W., Sun, Thomas Yang, Wakelee, Heather A., Madison, Russell, Schrock, Alexa B., Senaldi, Giorgio, Nakao, Naoki, Hanzawa, Hiroyuki, Tachibana, Masaya, Isoyama, Takeshi, Nakamaru, Kenji, Deng, Chenhui, Li, Meijing, Fan, Frank, Zhao, Qinying, Gao, Yanfei, Seto, Takashi, Jänne, Pasi A., Ou, Sai-Hong Ignatius·2020·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-20-1630

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Abstract

Purpose: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human U.S. phase I results of taletrectinib. Patients and Methods: Patients ≥18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation with overdose control was used (50–1,200 mg once daily or 400 mg twice daily). Primary objectives were safety/tolerability, and MTD determination. Secondary objectives were food-effect pharmacokinetics and antitumor activity. Results: A total of 46 patients were enrolled. Steady-state peak concentration (Cmax) and exposure (AUC0-8) increased dose dependently from 50-mg to 800-mg once-daily doses. The ratio of the geometric mean of AUC0-24 between low-fat-diet-fed/fasted state was 123% (90% confidence interval, 104%–149%). Dose-limiting toxicities (grade 3 transaminases increase) occurred in two patients (1,200-mg once-daily dose). MTD was 800 mg once daily. Most common treatment-related adverse events were nausea (47.8%), diarrhea (43.5%), and vomiting (32.6%). Pain score reductions were observed in the 800-mg once-daily dose cohort. Confirmed objective response rate was 33.3% among the six patients with RECIST-evaluable crizotinib-refractory ROS1+ NSCLC. One patient with TPM3-NTRK1 differentiated thyroid cancer achieving a confirmed partial response of 27 months at data cutoff. We identified a cabozantinib-sensitive ROS1 L2086F as an acquired taletrectinib-resistance mutation. Conclusions: Taletrectinib has manageable toxicities at the MTD of 800 mg daily. Preliminary efficacy was observed in patients with crizotinib-refractory ROS1+ NSCLC.

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Crossref · 10.1158/1078-0432.ccr-20-1630

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27 of 27 references verified0 citation errors · 0 not checkable

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  • Population PK of taletrectinib is similar in US and Japanese phase I studies.

    “A pooled population pharmacokinetics (PK) analysis indicated that population PK of taletrectinib is similar in US and Japanese phase I studies.21”

    From Taletrectinib in ROS1 + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [21]

  • The recommended phase II dose of taletrectinib is 600 mg once daily.

    “The recommended phase II dose (600 mg once daily) was established in two phase I trials conducted in the United States and Japan21,22 and confirmed during the safety lead-in of TRUST-I.20”

    From Taletrectinib in ROS1 + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [21]

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Metadata

Authors
Papadopoulos, K. P., Borazanci, E., Shaw, A. T., Katayama, R., Shimizu, Y., Zhu, V. W., Sun, T. Y., Wakelee, H. A., Madison, R., Schrock, A. B., Senaldi, G., Nakao, N., Hanzawa, H., Tachibana, M., Isoyama, T., Nakamaru, K., Deng, C., Li, M., Fan, F., Zhao, Q., Gao, Y., Seto, T., Jänne, P. A., & Ou, S.-H. I.
Affiliations
  • South Texas Accelerated Research Therapeutics (US)
  • HonorHealth (US)
  • Harvard University (US)
  • Japanese Foundation For Cancer Research (JP)
  • University of California, Irvine (US)
  • Stanford Medicine (US)
  • Foundation Medicine (United States) (US)
  • Daiichi Sankyo (United States) (US)
  • Daiichi Sankyo RD Novare (Japan) (JP)
  • Daiichi-Sankyo (Japan) (JP)
  • 12Linking Truth Technology Co, Ltd, Beijing, China.
  • 13AnHeart Therapeutics (Hangzhou) Company Ltd, Hangzhou, Zhejiang province, China.
  • National Hospital Organization Kyushu Cancer Center (JP)
  • 15Dana-Faber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2020-09-15
Volume
26
Issue
18
Pages
4785-4794
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-20-1630
OpenAlex
W3037915143
Cited by
113
References
27
Citations by year
2026: 10 · 2025: 17 · 2024: 22 · 2023: 15 · 2022: 25 · 2021: 17 · 2020: 7
FWCI
9.15
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Daiichi Sankyo, USA (DS6051-A-U101)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
  • Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Keywords
taletrectinib, tyrosine kinase inhibitors, acquired drug resistance, cabozantinib, neuroendocrine tumors, dose-limiting toxicity, maximum tolerated dose, objective response rate, first-in-human
MeSH terms
Adult, Aged, Female, Humans, Imidazoles, Male, Middle Aged, Neoplasm Staging, Neoplasms, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Pyridazines, Food-Drug Interactions, Maximum Tolerated Dose, Receptor, trkA, Protein Kinase Inhibitors, Young Adult, Response Evaluation Criteria in Solid Tumors

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