P1/2, N=12, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Oct 2024

P1, N=128, Recruiting, Xuanzhu Biopharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P1/2, N=133, Recruiting, Beijing Konruns Pharmaceutical Co., Ltd. | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Apr 2024 --> Oct 2025

P1, N=207, Recruiting, Beijing Konruns Pharmaceutical Co., Ltd. | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Jul 2023 --> Oct 2025

P1, N=43, Active, not recruiting, FindCure Biosciences (ZhongShan) Co., Ltd. | Recruiting --> Active, not recruiting

P1, N=78, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Apr 2025 --> Oct 2025

P1, N=0, Withdrawn, Washington University School of Medicine | N=36 --> 0 | Not yet recruiting --> Withdrawn

Patients taking MERTK inhibitors should be monitored by an ophthalmologist while on the drug. If toxicity develops, discussion of whether to continue the medication should take place between the patient, ophthalmologist, and oncologist, with consideration of the risks of vision loss versus benefits of taking the medication from a cancer perspective.

Altogether, we suggest that pioglitazone treatment exerts an anti-leukemic effect but concomitantly triggers a stroma-mediated resistance mechanism involving the Gas6/AXL axis. We demonstrate that a combination of pioglitazone with an AXL inhibitor overcomes this mechanism in primary cultures and AML cell lines and exerts potent anti-leukemic activity requiring further evaluation in vivo through murine xenograft pre-clinical models.

P1/2, N=22, Completed, Everfront Biotech Co., Ltd. | Active, not recruiting --> Completed | N=36 --> 22 | Trial completion date: Dec 2024 --> Sep 2024

AXL knockdown or AXL inhibition by bemcentinib reduces HR efficiency in HCC cells, and AXL plays its role in HR repair through its kinase activity...Mechanistically, AXL promotes the tyrosinization of RPA2 at tyrosine 9, promoting the phosphorylation of CHK1, thereby strengthens the HR repair ability in HCC cells to resist DNA damage. In conclusion, our results reveal that AXL is a promising therapeutic biomarker for HCC patients, and present that targeting AXL-RPA2-CHK1 pathway together with PARP inhibitor will be effective therapeutic strategy in HCC.

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2024 --> Aug 2025

Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.

UNC2025 was effective in both tumour types with superior efficacy over BGB324. Finally, we found that TAMs are expressed by tumour-associated macrophages in meningioma and schwannoma tumours and that UNC2025 strongly depleted macrophages in both tumour types.

P2, N=30, Recruiting, Beijing Konruns Pharmaceutical Co., Ltd.

"BerGenBio ASA...announced today a collaboration with Tempus...to advance the clinical development of BerGenBio's selective AXL inhibitor bemcentinib in first line (1L) Non-Small Cell Lung Cancer (NSCLC) patients with STK11 mutations (STK11m). BerGenBio's on-going BGBC016 Phase 1b/2a trial is designed to assess the benefit of adding bemcentinib to the current standard of care treatment (immunotherapy + doublet chemotherapy) in 1L STK11m patients, a population with poor outcomes and no specific therapies today.....Upon conclusion of the BGBC016 study, the parties intend to present insights derived from the resulting data to appropriate regulatory agencies as a next step in the further development of bemcentinib."

P1/2, N=92, Recruiting, SignalChem Lifesciences Corporation | Trial completion date: Dec 2027 --> Sep 2028 | Trial primary completion date: Dec 2025 --> Sep 2026

P1, N=87, Recruiting, Ono Pharmaceutical Co. Ltd

P1, N=78, Active, not recruiting, Ono Pharmaceutical Co. Ltd

Cell-based assays showed that triple therapy with osimertinib, ONO-7475, and the FGFR inhibitor BGJ398 significantly increased apoptosis by increasing expression of proapoptotic factor Bim and reduced cell viability compared with that observed for the osimertinib-ONO-7475 therapy. Xenograft models showed that triple therapy considerably suppressed tumor regrowth. A novel therapeutic strategy of additional initial FGFR1 inhibition may be highly effective in suppressing the emergence of osimertinib- and ONO-7475-resistant cells.

P1/2, N=44, Not yet recruiting, The University of Texas Health Science Center at San Antonio

P1/2, N=33, Not yet recruiting, FindCure Biosciences (ZhongShan) Co., Ltd.

P1, N=40, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Trial primary completion date: Dec 2025 --> Dec 2029

More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.

P1, N=6, Completed, BerGenBio ASA

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Aug 2024 | Trial primary completion date: Feb 2025 --> Aug 2024

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Jan 2034 --> Jun 2034 | Trial primary completion date: Jan 2029 --> Jun 2029

P1, N=32, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=12, Recruiting, University of Wisconsin, Madison | Trial completion date: Aug 2026 --> Jul 2027

P1, N=12, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting

Batiraxcept effectively reduced serum GAS6 levels at 1-h post-treatment, resulting in trough levels below the limit of detection in all cases but one. In conclusion, the combination of batiraxcept and durvalumab was safe and tolerable but did not demonstrate anti-tumor activity in a heterogenous population of patients with recurrent PROC.

Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.

The objective of this study is to assess the anti-cancer efficacy of trichostatin C (TSC), an analogue of trichostatin A sourced from the fermentation of Streptomyces sp...When combined with the DNMT inhibitor decitabine, TSC exhibits a synergistic anti-cancer effect...In conclusion, our findings suggest TSC as a promising anti-cancer agent with HDAC inhibitory activity. Furthermore, our results highlight the potential utility of TSC in combination with DNMT inhibitors for cancer treatment.

P1, N=67, Active, not recruiting, Pfizer | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

Its target engagement and selectivity were also confirmed by NanoBRET and cell-based MERTK and AXL phosphorylation assays. Compound 43 had excellent pharmacokinetic properties (large AUC and long half-life) and mediated antitumor activity against lung cancer cell lines, indicating its potential as a therapeutic agent.

P1, N=12, Not yet recruiting, University of Wisconsin, Madison

Instead, pharmacological blockade with the AXL inhibitors bemcentinib (BGB324), cabozantinib and NPS-1034 rapidly killed RMS cells in an AXL-independent manner, and augmented the efficacy of the chemotherapeutics vincristine and cyclophosphamide. In vivo administration of the combination of bemcentinib and vincristine exerted strong anti-tumoral activity in a rapidly progressing PDX mouse model, significantly reducing tumor bruden compared to single-agent treatment. Collectively, our data identify bemcentinib as a promising drug to improve chemotherapy efficacy in RMS patients.

P1/2, N=120, Recruiting, Qurient Co., Ltd. | Phase classification: P1b/2 --> P1/2

P3, N=490, Recruiting, Beijing Konruns Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.

Glesatinib had an acceptable safety profile in patients with advanced, pre-treated NSCLC with MET activating alterations. Modest clinical activity was observed, which likely reflects suboptimal drug bioavailability suggested by previously reported Phase I data, and pharmacodynamic findings of lower than anticipated increases in circulating soluble shed MET ectodomain (s-MET).

P1, N=23, Completed, University of Texas Southwestern Medical Center | Active, not recruiting --> Completed | Trial completion date: May 2027 --> Apr 2023