Cabometyx (cabozantinib tablet)

P2, N=40, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended

P=N/A, N=388, Completed, Takeda | Active, not recruiting --> Completed

P2, N=102, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025

P1, N=43, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting | N=21 --> 43

P3, N=1250, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

P2, N=109, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Sep 2024

P1, N=20, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=44, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

P3, N=1250, Not yet recruiting, Gustave Roussy, Cancer Campus, Grand Paris

When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting programed cell death protein 1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.

Cabozantinib shows promising activity in patients with MPPGs.

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2024 --> Sep 2024

P2, N=152, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Dec 2024 | Trial primary completion date: Oct 2020 --> Oct 2023

P1/2, N=6, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting | N=46 --> 6 | Trial completion date: Jul 2026 --> Jan 2027

P2, N=1500, Recruiting, Bristol-Myers Squibb | N=800 --> 1500 | Trial completion date: Aug 2025 --> Aug 2029 | Trial primary completion date: Aug 2025 --> Aug 2029

P2, N=29, Recruiting, University of Arizona | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=125, Active, not recruiting, National Cancer Institute (NCI)

P1, N=21, Suspended, M.D. Anderson Cancer Center | N=36 --> 21 | Recruiting --> Suspended

P2, N=90, Not yet recruiting, Ipsen

The factors described make it possible to predict the incidence of AEs, which allows for faster detection and easier management, especially in the high-risk group. AEs should be reported in detail in real-world studies, as their occurrence has a significant impact on prognosis.

P1, N=12, Active, not recruiting, University of California, Irvine | Trial completion date: Jan 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Aug 2023

P2, N=127, Active, not recruiting, Ipsen | Trial completion date: Nov 2024 --> Sep 2099

P3, N=522, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Mar 2024 --> Jun 2024

Among these, the trials administering drugs Alisertib or Cabozantinib, which target AURKA or receptor tyrosine kinases, respectively, appear to have promising results...Consequently, the landscape of successful treatment regimens for NEPC is extremely limited. These trial results and the literature on the topic emphasize the need for new preventative measures, diagnostics, disease specific biomarkers, and a thorough clinical understanding of NEPC.

Recently, several TKIs, for instance regorafenib and cabozantinib, have showed clinical interest in treating osteosarcoma and target both vascular endothelial growth factor receptor (VEGFR) and mesenchymal epithelial transition factor (c-MET)...More importantly, BMS-794833 and anlotinib exerted synergistic therapeutic effects against osteosarcoma in vivo. Altogether, this study reveals a new (VEGFR)-targeting drug that can be combined with anlotinib for the treatment of osteosarcoma, which provides an important theoretical basis for overcoming anlotinib resistance.

P2, N=50, Recruiting, Rana McKay, MD | Trial primary completion date: Feb 2024 --> May 2024

P2, N=35, Recruiting, National Cancer Institute, Naples | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

P3, N=187, Active, not recruiting, Exelixis | Trial completion date: Dec 2023 --> Dec 2024

P3, N=654, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P3, N=837, Active, not recruiting, Exelixis | Trial completion date: Dec 2023 --> Dec 2024

P2, N=20, Recruiting, University Health Network, Toronto | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

P2, N=48, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025

P2, N=66, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P=N/A, N=150, Recruiting, Ipsen | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Feb 2024 --> Dec 2024

P2, N=36, Active, not recruiting, University of Utah | Trial completion date: May 2026 --> May 2024 | Trial primary completion date: May 2024 --> Aug 2023

Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

P2, N=105, Active, not recruiting, Washington University School of Medicine | Trial completion date: Aug 2028 --> Jun 2029 | Trial primary completion date: Feb 2025 --> Jun 2024

We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

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.

P2, N=86, Recruiting, Fox Chase Cancer Center | N=49 --> 86 | Trial completion date: Feb 2025 --> Feb 2027 | Trial primary completion date: Feb 2024 --> Feb 2026

While c-MET inhibitors such as crizotinib, capmatinib, tepotinib and cabozantinib have garnered FDA approval for non-small cell lung cancer (NSCLC), their potential within breast cancer therapy is still undetermined...Furthermore, we highlight the pivotal role of c-MET-targeted therapies in breast cancer, offering a clinical perspective on this promising avenue of intervention. In this pursuit, we strive to unravel the potential of c-MET as a beacon of hope in the fight against breast cancer, unveiling new horizons for therapeutic innovation.

Sorafenib, lenvatinib, and cabozantinib are multikinase inhibitors approved for patients with metastatic RAI-refractory DTC, whereas vandetanib and cabozantinib are approved for patients with MTC. Management of thyroid carcinomas has evolved such that targeted therapies have become therapeutic options for patients with BRAF, RET, NTRK, ALK, and ROS1 alterations and even have reported efficacy in anaplastic thyroid carcinomas. In this article, we review the advances made over the years in the treatment of metastatic thyroid carcinoma and focus on the systemic therapies that have recently transformed the treatment landscape of advanced disease.