Inlyta (axitinib)

P2, N=54, Recruiting, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Enrolling by invitation --> Recruiting | Trial completion date: Mar 2024 --> Dec 2027 | Trial primary completion date: Mar 2023 --> May 2027

P1, N=5, Terminated, Abramson Cancer Center at Penn Medicine | Phase classification: P1b --> P1 | N=25 --> 5 | Trial completion date: Dec 2024 --> Apr 2024 | Recruiting --> Terminated; failure to accrue

In brief, FPPT@Axi is prepared by utilizing an NRP-1-targeting chimeric peptide (Fmoc-K(PpIX)-PEG8-TKPRR) to encapsulate the antiangiogenic drug Axitinib (Axi)...Consequently, FPPT@Axi spatiotemporally restrains the tumor growth through blocking angiogenesis, destroying tumor vessels, and inducing tumor apoptosis. Such an NRP-1-mediated targeting codelivery system sheds light on constructing an appealing candidate with translational potential by using clinically approved PDT and chemotherapy.

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

Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.

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.

On the contrary, some patients with mucosal, acral or KIT-mutant melanoma may benefit from TKI-based therapies. Further studies focused on biomarker discovery and randomized trials are necessary to better understand the role of VEGFR1-3 as a therapeutic target in melanoma.

P2, N=41, Active, not recruiting, West China Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Mar 2025

P3, N=61, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=262 --> 61 | Trial completion date: May 2025 --> Sep 2026 | Trial primary completion date: May 2025 --> Sep 2026

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

By investigating the Genomics of Drug Sensitivity in Cancer (GDSC) database, we identified axitinib and taselisib as candidate compounds that could potentially target the KISS-high myeloblasts. Altogether, our findings suggest that KISS holds the potential to improve the current prognostic scheme of MDS and inform novel therapeutic opportunities.

P1/2, N=145, Recruiting, Incyte Corporation | Not yet recruiting --> Recruiting

P3, N=861, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Dec 2023 --> Dec 2025

Lastly, we identified RTN1 as a potential biomarker, exhibiting lower expression in sensitive rare-tumor PDX models prior to Axitinib and Vandetanib treatment.ConclusionsWith the multi-omics datasets comprising proteomics/phospho-proteomics, RNA-Seq and WES datasets from the NCI Patient Derived Models Repository cohort, we were able to query some important cancer biological processes at a higher resolution. In addition, we revealed gene- and pathway-level regulatory differences from various histologies. Overall, the multi-omics data from PDX models showed promising recapitulation of original tumor activity and should continue to serve as an amenable and scalable drug screening platform for pre-clinical trials.

P2, N=31, Active, not recruiting, Yana Najjar | Recruiting --> Active, not recruiting | Trial completion date: Jul 2026 --> Feb 2029

P1, N=30, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P1, N=72, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=20, Not yet recruiting, RenJi Hospital

The present study reveals the significance of NK cells in HNSC and their potential as prognostic biomarkers. The CFKZ score offers a promising approach for predicting patient outcomes and guiding personalized treatment decisions in HNSC. These findings contribute to our understanding of HNSC immunobiology and hold implications for precision medicine in HNSC management.

P3, N=262, Recruiting, Pfizer | Trial completion date: Dec 2025 --> May 2025 | Trial primary completion date: Dec 2025 --> May 2025

Axitinib-treated patients carrying the ACE deletion allele suffered more frequently from hand-foot syndrome and a deterioration in kidney function (p  = .045 and p =  0.005, respectively) whereas those carrying the NOS3 G allele suffered more frequently from proteinuria and multiple AEs (p  = .025 and p =  0.036, respectively). Our study found that the ACE deletion allele and the NOS3 G allele are associated with increased AEs.

In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.

This study analyzed the extensive regulatory mechanisms of m6A modification on oxidative stress, the tumor microenvironment, and immunity. Quantifying m6A scores may enhance immunotherapeutic effects and assist in developing more effective agents.

ICRTGs may be reliable biomarkers for the molecular typing of patients with OVC, enabling the prediction of prognosis and immunotherapy efficacy.

P2, N=65, Completed, Institute of Cancer Research, United Kingdom | Unknown status --> Completed

P2, N=72, Recruiting, Centre Leon Berard | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jul 2024 --> Oct 2024

P2, N=30, Not yet recruiting, Peking University Cancer Hospital & Institute

Our findings suggest that patients presenting higher STX4 levels may exhibit enhanced responsiveness to immunotherapy and higher sensitivity to the medications axitinib and everolimus. Finally, we propose STX4 expression assessment as a novel approach to predict patient response to respective immunotherapies and targeted treatments, hence potentially improving patient outcomes.

Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC.

P=N/A, N=171, Completed, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed

P2, N=31, Recruiting, Yana Najjar | Trial completion date: Dec 2025 --> Jul 2026 | Trial primary completion date: Sep 2023 --> Apr 2024

Besides, compared to the low-risk group, there were higher expressions of most immune checkpoint genes and HLA genes in the high-risk group, and the high-risk patients showed higher sensitivity to the chemotherapy and targeted drugs (axitinib, dasatinib, pazopanib, saracatinib, sunitinib and temsirolimus). The novel CRG signature may act as a reliable, efficient tool for prognostic prediction and treatment guidance in future clinical practice.

P1, N=88, Recruiting, Nanjing Leads Biolabs Co.,Ltd | Trial completion date: Apr 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

Other drugs, such as imatinib, figitumumab, axitinib, and eribulin, are also being tested. Definitive radiotherapy appears to be a promising therapeutic modality. Since standards for the treatment of advanced and metastatic diseases are not available, further investigation of novel agents is necessary.

TFEB-altered RCC is an extremely rare variant, exhibited mixed morphological characteristics. The radiological feature lack specificity, resembling clear cell RCC or papillary RCC. Genetic analyses including FISH analysis is crucial in the diagnosis of TFEB-altered RCC. For localized TFEB-altered RCC, both radical nephrectomy and partial nephrectomy conferred satisfactory prognosis. For metastatic TFEB-altered RCC, immunotherapy-based drug combinations could be a promising treatment strategy.

P1/2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=39 --> 23

For metastatic patients, 3 received first-line therapy (1 axitinib, 1 axitinib + sintilimab, 1 sunitinib), 2 received second-line therapy (1 axitinib + sintilimab, 1 axitinib + toripalimab), 1 received third-line therapy (axitinib + toripalimab + everolimus). MED15-TFE3 rRCC mainly present low-grade cystic renal neoplasm with favorable prognosis. For metastatic MED15-TFE3 rRCC, there is no standard therapy. And the transcriptomic evidence may provide insights for future research.

Angio TRS was then validated in a separate cohort of 86 patients with RCC treated with single agent systemic VEGFR TKI (median follow-up 29.2 months; 76% male, 77% clear cell, 14% with sarcomatoid features, 84% 1st line, and 71% treated with sunitinib, pazopanib or axitinib); 52% of patients were Angio TRS High. Angio TRS is a multivariate expression-based algorithm performed on FFPE tumor tissue, validated to be prognostic of clinical outcome for patients with RCC treated with single agent VEGFR TKI when controlling for clinical factors. Angio TRS may support individualized treatment decision making in patients with advanced RCC. Additional independent validation in a cohort of Kaiser Permanente patients will be presented.

Patients receiving 1L IO-IO (n = 471; nivolumab plus ipilimumab) or IO+TKI regimens (n = 353; pembrolizumab plus axitinib [63.7%], nivolumab plus cabozantinib [21.8%], pembrolizumab plus lenvantinib [14.4%]) had similar baseline characteristics with the exception of health plan type, body mass index, and risk score (Table 1)... The study described treatment patterns for mRCC and found patients receiving 1L IO-IO and IO+TKI regimens were similar demographically, though IO-IO patients started with poorer risk scores. Although IO-IO was associated with higher treatment costs in the first 3 months, the subsequent monthly costs were lower vs IO+TKI. Results also indicated that retreatment with IO in the 2L setting is occurring in real-world practice.aHierarchically selected IMDC (calculated with lab data) before MSKCC (calculated) and CCQP (as reported by providers) risk scores.

Clinical Trial Registration Number: NCT05817903 Sponsored by Pfizer Background: The combination of nivolumab plus ipilimumab (N+I) is able to increase the overall survival (OS), progression free survival (PFS) and overall response rate (ORR) compared to sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC) at intermediate or poor prognosis. However, the rate of pts with partial response to N+I (32%) is lower of that reported with the combination of axitinib plus pembrolizumab (51%)...The trial is actively recruiting. Clinical trial information: NCT05817903.

Background: In patients with previously untreated aRCC, A + Ax combination therapy has shown superior progression-free survival (PFS) and objective response rate (ORR) vs sunitinib across all International Metastatic RCC Database Consortium (IMDC) risk groups. In this UK-based real-world study of first-line A + Ax treatment in patients with aRCC, OS, PFS, ORR, and best response observed at 36 months were in line with findings from clinical trials, with no newly emerging AEs.