Multikinase Inhibition with Tinengotinib in Advanced Solid Tumors: Results from a Multicenter Phase Ib/II Trial
10 affiliations
- 1Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- 2Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
- 3Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, California.
- 4Department of Oncology, Gabrail Cancer Center, Canton, Ohio.
- 5Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
- 6Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California.
- 7TransThera Sciences (US), Inc., Gaithersburg, Maryland.
- 8TransThera Sciences (Nanjing), Inc., Nanjing, China.
- 9Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- 10Department of Medical Oncology, Rutgers Cancer Center Institute, New Brunswick, New Jersey.
Abstract
Purpose:: Tinengotinib, a multikinase inhibitor targeting Aurora kinases A/B, fibroblast growth factor receptors (FGFRs) 1 to 3, vascular endothelial growth factor receptor 2, and Janus kinases 1 to 2, was evaluated in this phase Ib/II study to assess safety, pharmacokinetics (PK), efficacy, and genomic correlates of response and resistance in patients with advanced solid tumors.
Patients and Methods:: Patients with advanced/metastatic solid tumors lacking standard treatment options were enrolled at 7 sites in the United States (NCT04742959). Tinengotinib was administered at 12 mg once daily in arm A and at multiple dose levels/dosing schedules in arm C.
Results:: Among 197 patients receiving tinengotinib, treatment-related treatment-emergent adverse events occurred in 160 (81.2%) patients, with hypertension being the most common. Hyperphosphatemia and ocular toxicities were uncommon. Clinical benefit was achieved by 43 of 159 (27.0%) evaluable patients, including 1 complete response, 20 partial responses, and 22 stable diseases ≥6 months. Antitumor activity was most pronounced with 10-mg and 12-mg dose levels. The objective response rates were 33.3%, 30%, and 13% in prostate cancer (n = 15), breast cancer (n = 20), and cholangiocarcinoma (n = 23), respectively. PK analyses supported the 10-mg once-daily regimen. Exploratory genomic analyses identified potential molecular correlations of response, including FGFR2 fusions in cholangiocarcinoma responders. Additional observations in breast cancer, including ROS1 alterations, were exploratory and should be considered hypothesis generating. Exploratory analyses also suggested associations between EGFR or MLL mutations in cholangiocarcinoma and MYC alterations in prostate cancer with shorter progression-free survival, consistent with emerging evidence linking MYC-driven lineage plasticity to androgen receptor–independent disease biology. Reductions in circulating tumor DNA variant allele frequency further supported pharmacodynamic target engagement.
Conclusions:: Tinengotinib demonstrated manageable toxicity with antitumor activity across advanced solid tumors, with infrequent hyperphosphatemia and ocular toxicities. Integrated PK–biomarker analyses support the continued clinical development of tinengotinib and the exploration of biomarker-informed precision oncology strategies.
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BibTeX
@article{pihapaul2026multikinase,
title = {{Multikinase Inhibition with Tinengotinib in Advanced Solid Tumors: Results from a Multicenter Phase Ib/II Trial}},
author = {Sarina A. Piha-Paul and Chih-Yi Liao and Farshid Dayyani and Nashat Y. Gabrail and Syed Mohammad Ali Kazmi and Sayeh Moazami Lavasani and Katie Hennessy and Shumao Ni and Caixia Sun and Hui Wang and Peng Peng and Frank Wu and Milind M. Javle and Jean Fan and Sanjay Goel},
journal = {Clinical Cancer Research},
year = {2026},
month = jul,
doi = {10.1158/1078-0432.ccr-26-1076},
url = {https://doi.org/10.1158/1078-0432.ccr-26-1076},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multikinase Inhibition with Tinengotinib in Advanced Solid Tumors: Results from a Multicenter Phase Ib/II Trial
AU - Sarina A. Piha-Paul
AU - Chih-Yi Liao
AU - Farshid Dayyani
AU - Nashat Y. Gabrail
AU - Syed Mohammad Ali Kazmi
AU - Sayeh Moazami Lavasani
AU - Katie Hennessy
AU - Shumao Ni
AU - Caixia Sun
AU - Hui Wang
AU - Peng Peng
AU - Frank Wu
AU - Milind M. Javle
AU - Jean Fan
AU - Sanjay Goel
PY - 2026
DA - 2026/07/23
JO - Clinical Cancer Research
DO - 10.1158/1078-0432.ccr-26-1076
UR - https://doi.org/10.1158/1078-0432.ccr-26-1076
AB - Purpose:: Tinengotinib, a multikinase inhibitor targeting Aurora kinases A/B, fibroblast growth factor receptors (FGFRs) 1 to 3, vascular endothelial growth factor receptor 2, and Janus kinases 1 to 2, was evaluated in this phase Ib/II study to assess safety, pharmacokinetics (PK), efficacy, and genomic correlates of response and resistance in patients with advanced solid tumors. Patients and Methods:: Patients with advanced/metastatic solid tumors lacking standard treatment options were enrolled at 7 sites in the United States (NCT04742959). Tinengotinib was administered at 12 mg once daily in arm A and at multiple dose levels/dosing schedules in arm C. Results:: Among 197 patients receiving tinengotinib, treatment-related treatment-emergent adverse events occurred in 160 (81.2%) patients, with hypertension being the most common. Hyperphosphatemia and ocular toxicities were uncommon. Clinical benefit was achieved by 43 of 159 (27.0%) evaluable patients, including 1 complete response, 20 partial responses, and 22 stable diseases ≥6 months. Antitumor activity was most pronounced with 10-mg and 12-mg dose levels. The objective response rates were 33.3%, 30%, and 13% in prostate cancer (n = 15), breast cancer (n = 20), and cholangiocarcinoma (n = 23), respectively. PK analyses supported the 10-mg once-daily regimen. Exploratory genomic analyses identified potential molecular correlations of response, including FGFR2 fusions in cholangiocarcinoma responders. Additional observations in breast cancer, including ROS1 alterations, were exploratory and should be considered hypothesis generating. Exploratory analyses also suggested associations between EGFR or MLL mutations in cholangiocarcinoma and MYC alterations in prostate cancer with shorter progression-free survival, consistent with emerging evidence linking MYC-driven lineage plasticity to androgen receptor–independent disease biology. Reductions in circulating tumor DNA variant allele frequency further supported pharmacodynamic target engagement. Conclusions:: Tinengotinib demonstrated manageable toxicity with antitumor activity across advanced solid tumors, with infrequent hyperphosphatemia and ocular toxicities. Integrated PK–biomarker analyses support the continued clinical development of tinengotinib and the exploration of biomarker-informed precision oncology strategies.
SN - 1078-0432
SN - 1557-3265
ER -