Tinengotinib Shows Early Tolerability, Efficacy Signals in Heavily Pretreated mCRPC


Tinengotinib elicited responses with a manageable safety profile in heavily pretreated patients with metastatic castration-resistant prostate cancer.

María Teresa Bourlon, MD, MSc, MS

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The spectrum-selective multikinase inhibitor tinengotinib showed preliminary evidence of clinical benefit with a manageable toxicity profile when utilized as a monotherapy in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from 3 early-phase trials (NCT03654547, NCT04742959, NCT05253053) presented during the 2024 Genitourinary Cancers Symposium.1

In the 22 efficacy-evaluable patients, tinengotinib induced an objective response rate of 46.2%, with 6 of 13 patients achieving a partial remission. The disease control rate (DCR) achieved with the agent was 84.6%. Moreover, the median radiographic progression-free survival (PFS) was 5.6 months (95% CI, 3.29-7.29), and 43% out of 14 evaluable patients achieved a prostate-specific antigen (PSA) decline of at least 50% (PSA50) from baseline.

“Further study of tinengotinib as monotherapy or in combination for relapsed or refractory mCRPC is warranted,” lead study author Hongquian Guo, MD, of Nanjing Drum Tower Hospital in Nanjing, China, and colleagues, wrote in a poster of the data.

To participate in the phase 1 TT420X2101 (n = 1), phase 1b/2 TT420X1103 (n = 10), or the phase 1b/2 TT00420CN04 (n = 19) studies, which were conducted in the United States and China, patients were required to be at least 18 years of age, have mCRPC with no available standard treatment options, an ECOG performance status of 0 or 1, and acceptable organ function.

Participants were given continuous tinengotinib orally at daily doses ranging from 8 mg (n = 1), to 10 mg (n = 19), to 12 mg (n = 10). Treatment continued until disease progression or intolerable toxicity.

The primary outcome measure of the studies was to examine dose-limiting toxicities (DLTs). Efficacy measures included evaluating ORR, DCR, duration of response, PFS, and overall survival, among others. Investigators utilized serum PSA to examine PSA50 response, and Common Terminology Criteria for Adverse Events v.5 for safety assessments.

At a data cutoff date of August 28, 2023, a total of 30 patients had received tinengotinib. The median patient age was 67 years (range, 52-83). The majority of patients had an ECOG performance status of 1 (93.3%) and stage IV disease (93.3%). Moreover, 13.3% of patients received 2 prior lines of antineoplastic therapies and 86.7% received 3 or more prior lines. Previous treatment included docetaxel (76.7%), abiraterone acetate (Zytiga; 86.7%), and enzalutamide (Xtandi; 36.7%).

Treatment-emergent adverse effects (AEs) were experienced by 97% of patients; 93% of patients had treatment-related AEs (TRAEs). Grade 3 or 4 TRAEs occurred in 53.3% and 3.3% of patients, respectively. No grade 5 TRAEs occurred.

The most common TRAEs included increased blood thyroid-stimulating hormone (grade 1 or 2, 43.3%; grade 3 or 4, 0%), anemia (26.7%; 10.0%), hypertension (10.0%; 16.7%), decreased white blood cell count (20.0%; 0%), prolonged electrocardiogram QT (20.0%; 0%), and increased aspartate aminotransferase (26.7%; 10.0%).

TEAEs led to dose interruptions in 66.7% of patients and dose reductions in 3.3% of patients. TRAEs led to dose interruptions and reductions in 63.3% and 3.3% of patients, respectively. Notably, no patients discontinued tinengotinib because of TRAEs.


Hongqian G, Subudhi SK, Han W, et al. Efficacy and safety of tinengotinib in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2024;42(suppl 4):133. doi:10.1200/JCO.2024.42.4_suppl.133

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