famitinib (SHR 1020)

P2, N=620, Recruiting, Fudan University | N=140 --> 620

P2, N=0, Withdrawn, Jiangsu Province Nanjing Brain Hospital | N=28 --> 0 | Recruiting --> Withdrawn

P2, N=716, Recruiting, Fudan University | Phase classification: P1/2 --> P2

P2, N=130, Not yet recruiting, Fudan University

We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023...The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

Lastly, murine experiments and scRNA-seq analysis of a treated patient's tumor demonstrated that Famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. Conclusively, we displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

P2, N=40, Not yet recruiting, Harbin Medical University

P3, N=424, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P3, N=185, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=304 --> 185 | Recruiting --> Terminated; R&D strategy adjustment

These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway.

P2, N=28, Recruiting, Qian Chu

P2; Trial completion date: Nov 2023 --> Dec 2024 | Trial primary completion date: Nov 2023 --> May 2023

Adverse events were limited and manageable. This is the first report of such a treatment regimen being applied in a clinical setting, suggesting that the SHR-1701 and famitinib combination may be a promising immunotherapeutic approach for patients with refractory advanced GBC.

This trial was registered at http://www.chinadrugtrials.org.cn/index.html. (Registration number: CTR20201824.).

P2, N=28, Recruiting, Qian Chu | Trial primary completion date: Jun 2023 --> Dec 2023

However, the role of angiogenesis inhibitors, such as bevacizumab, in these patients (pts) is controversial...Our phase Ib/II trial (NCT05176080, ChiCTR2100053950) aims to evaluate the safety and efficacy of a novel anti-angiogenesis TKI famitinib (F) added to dalpiciclib (D) and ET in advanced HR-positive and HER2-negative BC... The anti-angiogenesis multi-targeted receptor TKI famitinib combined with CDK4/6i and fulvestrant has shown antitumor effects in advanced HR-positive and HER2-negative BC, and no new safety signals were observed.

P2, N=233, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

P3, N=424, Not yet recruiting, Fudan University

P1, N=3, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=76 --> 3 | Trial completion date: Oct 2023 --> Jun 2023 | Recruiting --> Terminated; Sponsor R & D Strategy Adjustment

To our knowledge, this is the best over survival reached in first-line treatment of advanced TNBC. A randomized controlled FUTURE-Super trial (NCT04395989) is ongoing to further validate these findings.

Treatment-related death was reported in two pts (1.9%) in cohort A (acute coronary syndrome, infection and sepsis). Table: LBA44 Summary of efficacy Cohort A (n=105) Cohort B (n=54) Cohort C (n=35) BICR-assessed CR 9 (8.6) 3 (5.6) — PR 34 (32.4) 10 (18.5) — ORR 41.0 (31.5-51.0) 24.1 (13.5-37.6) — DCR 75.2 (65.9-83.1) 55.6 (41.4-69.1) — PFS (mo) 7.2 (6.1-12.4) 4.0 (2.1-6.1) — Investigator-assessed CR 4 (3.8) 2 (3.7) 1 (2.9) PR 41 (39.0) 10 (18.5) 4 (11.4) ORR 42.9 (33.2-52.9) 22.2 (12.0-35.6) 14.3 (4.8-30.3) DCR 74.3 (64.8-82.3) 53.7 (39.6-67.4) 42.9 (26.3-60.7) PFS (mo) 8.1 (6.2-12.4) 4.1 (2.1-5.1) 2.9 (2.0-6.2) 12-months OS rate 80.3 (70.7-87.0) 71.9 (55.8-83.0) 59.7 (40.9-74.3) Conclusions CAM plus FAM showed improved antitumor activity than CAM alone or investigator's choice of chemo in pts with R/M CC, with a tolerable safety profile.

Camrelizumab plus famitinib demonstrated encouraging clinical activity with manageable safety profile in previously treated patients with advanced NSCLC. The results warranted further validation.

Further studies are needed to confirm and expand these findings. Jiangsu Hengrui Pharmaceutical Co., Ltd.

P1, N=70, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

P2, N=0, Withdrawn, Jiangsu HengRui Medicine Co., Ltd. | N=168 --> 0 | Not yet recruiting --> Withdrawn

P1, N=28, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

P2, N=139, Active, not recruiting, Fudan University | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2022 --> Nov 2023

P1/2, N=65, Active, not recruiting, Henan Cancer Hospital | Recruiting --> Active, not recruiting

P2, N=35, Active, not recruiting, Tianjin Medical University Cancer Institute and Hospital | Recruiting --> Active, not recruiting | Trial completion date: Aug 2022 --> Sep 2023 | Trial primary completion date: May 2022 --> Aug 2022

P3, N=223, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P3, N=223, Not yet recruiting, Fudan University

P2, N=46, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P2, N=46, Not yet recruiting, Fudan University

P2, N=140, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P2, N=194, Active, not recruiting, Jiangsu HengRui Medicine Co., Ltd. | Recruiting --> Active, not recruiting

P2, N=140, Not yet recruiting, Fudan University

Famitinib can synergize with radioimmunotherapy by regulating the tumor immune microenvironment in murine lung cancer.

Co-administration of rifampin considerably reduces plasma concentration of famitinb due to CYP3A4 induction. Concomitant administration of famitinib and strong CYP3A4 inducers should be avoided, whereas when simultaneous use with inducers of CYP3A4, dose adjustment of famitinb is recommended.

We investigated the safety and efficacy of famitinib, a tyrosine kinase inhibitor (TKI) of angiogenesis, combined with the bifunctional fusion protein SHR-1701 targeting PD-L1 and TGF-β in patients (Pts) with chemotherapy-refractory sarcoma. Pts were eligible if they were aged 12 years or older, and had histologically confirmed advanced or metastatic sarcomas; the presence of measurable disease according to RECIST 1.1; an ECOG performance status of 0-1; progressive disease after at least one line of adriamycin containing chemotherapy; MSI-H or TMB>5 or PD-L1≥1% except for alveolar soft-part sarcoma (ASPS) and undifferentiated pleomorphic sarcoma (UPS). Famitinib plus SHR-1701 has manageable toxicity and preliminary activity in pts with advanced sarcomas, warranting further investigation.

P2, N=265, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Unknown status --> Recruiting | Trial completion date: Jun 2021 --> Dec 2022 | Trial primary completion date: Jun 2020 --> Dec 2022

P=N/A, N=38, Completed, Peking University People's Hospital | Recruiting --> Completed | Trial completion date: Sep 2021 --> Dec 2021 | Trial primary completion date: Jul 2021 --> Oct 2021

P2, N=124, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Recruiting