P1/2, N=180, Completed, Sun Yat-sen University Cancer Center; Haihe Biopharma Co.,Ltd.

Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer.

P2, N=100, Recruiting, GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. | Trial completion date: Jul 2025 --> Dec 2027 | Trial primary completion date: Jul 2025 --> Dec 2027

P2, N=15, Completed, Grupo Espanol de Investigacion en Sarcomas | Recruiting --> Completed | N=39 --> 15

P2, N=46, Active, not recruiting, National Cancer Institute, Naples | Trial completion date: Nov 2022 --> Nov 2024 | Trial primary completion date: Nov 2021 --> Nov 2024

P2, N=28, Recruiting, Sun Yat-sen University | Unknown status --> Recruiting | N=43 --> 28 | Trial completion date: Jul 2020 --> Jul 2023 | Trial primary completion date: Jul 2020 --> Feb 2023

In real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.

VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

No abstract available

Fruquintinib, regorafenib, trifluridine/tipiracil (TAS-102), panitumumab and cetuximab combined with single-agent chemotherapy regimens are currently recommended as third-line therapies for patients exhibiting disease progression...The mFOLFOX6 regimen was administered...Liver metastases (intestinal-type adenocarcinoma) were detected in November 2018, and second-line therapy with the FOLFIRI regimen was initiated in January 2019...Third-line therapy with fruquintinib, raltitrexed, and S-1 achieved a PR that permitted surgical resection and enabled a relatively long progression-free survival. The findings suggest that the three agents regimen might be clinically effective as late-line therapy for mCRC.

This analysis of real-world data found that OS was similar for patients with mCRC who were treated with TAS-102 compared with regorafenib. Median OS with both agents in a real-world setting was similar to that shown in the clinical trials that led to their approvals. A prospective trial comparing TAS-102 and regorafenib would unlikely change current management of patients with refractory mCRC.

AAV-shBcrp-treated mice showed higher M - 5 concentration in plasma and liver, but lower biliary excretion than the control mice, indicating the fundamental role of hepatic Bcrp in M - 5 disposition. This is the first application of AAV-knockdown strategy to clarify the pharmacokinetic role of xenobiotic efflux transporters in the liver.

P2, N=123, Completed, Academic and Community Cancer Research United | Trial completion date: Jun 2025 --> Mar 2023 | Active, not recruiting --> Completed

Our results demonstrated a different benefit from third-line anti-EGFR-based therapy according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T. At the same time, no difference was observed in R-sided tumor.

Patients with unresectable HCC receive systemic therapies, traditionally sorafenib or lenvatinib as first line therapy. Importantly, combined inhibition of EGFR and Lyn kinase in sorafenib resistant tumor spheroids are effective in inducing cell death. Our model proved to be an affordable and useful model to mimic drug resistant tumor microenvironment in HCC and provided novel insights into candidates for new combinational therapies.

Glioma m6A clusters and gene signatures have distinctive TME features. The m6A gene signature may guide prognostic assessments and promote the use of effective strategies.

The difference in the incidence of TRAEs between the two groups was not statistically significant (P> 0.05). Compared to regorafenib plus ICIs, regorafenib plus ICIs with TACE was tolerated and improved survival as the second-line treatment for patients with advanced HCC.

This report suggests that the analysis of multiple cytokines might identify a cytokine signature related to a patient's outcome that is able to recognize patients who will benefit from treatment. If confirmed, future studies, also based on different drugs, using this approach and including larger patient populations, might identify a signature allowing the a priori identification of patients to be treated.

The most common change was the use of sunitinib and regorafenib in patients with SDH-deficient GIST. The mutation testing rates at primary care centres continue to be low. Despite the hurdles, a large percentage of our patients underwent molecular testing, aiding in therapeutic decision-making.

Sunitinib and regorafenib are approved in the second- and third-line setting, respectively, with activity against certain secondary mutations with comparatively much lower response rates and survival increment compared to imatinib. Although the efficacy of ripretinib in this unselected patient population was not significantly different from that of sunitinib, the tolerability profile was better. This review article aims to review the efficacy and tolerability profile of ripretinib, together with its role in the setting of unresectable or metastatic GIST.

P2, N=0, Withdrawn, CytoDyn, Inc.

Notably, survival improved for patients with BRAF mutant as well as microsatellite unstable (MSI-H) tumors. Multivariate regression analysis identified surgical resection of liver metastasis (HR = 0.26, 95% CI, 0.19-0.37), use of immunotherapy (HR = 0.44, 95% CI, 0.29-0.67) and use of third line chemotherapy (regorafenib or trifluridine/tipiracil, HR = 0.74, 95% CI, 0.58-0.95), but not year of diagnosis (HR = 0.99, 95% CI, 0.98-1), as associated with better survival, suggesting that increased use of these therapies are the drivers of the observed improvement in survival.

The major grade 3 and4 toxicities were proteinurea (29%), hypertension (26%), hand-foot syndrome(15%), and platelet decrease (6%). Regorafenib after TFTD plus bevacizumab showed efficacy similar to that of the previous study, and no new adverse events were observed.

MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies.

P2, N=49, Active, not recruiting, Centre Hospitalier Universitaire de Besancon | Trial primary completion date: Jan 2023 --> Jul 2023

P2, N=425, Recruiting, Centre Leon Berard | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Feb 2024 --> Feb 2026

Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are second-line therapy. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

P2, N=90, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2022 --> Jan 2024 | Trial primary completion date: Jun 2022 --> Jan 2023

In addition, the study did not meet its primary endpoint. Analysis of circulating tumor DNA (ctDNA) dynamics during study treatment is ongoing.

P=N/A, N=300, Completed, Bayer | Active, not recruiting --> Completed

P2, N=49, Active, not recruiting, Centre Hospitalier Universitaire de Besancon | Recruiting --> Active, not recruiting

Manipulation of miR‑126‑3p either by enforced expression using pre‑miR‑126‑3p or by inhibition using antimiR‑126‑3p did not alter tumor cell viability, proliferation or sensitivity to either sorafenib or regorafenib. Within LC/HSC spheroids, ADAM9 and vascular endothelial growth factor expression was increased by silencing of miR‑126‑3p but diminished with the restoration of miR‑126‑3p. These studies implicate miR‑126‑3p in functional effects on migration, invasion and spheroid growth of tumor cells in the presence of HSCs, and thereby demonstrate functional EV‑RNA‑based intercellular signaling between HSCs and LC cells that is directly relevant to tumor‑cell behavior.

After ICIs, offering multikinase inhibitors is a widespread approach, either shifting forward sorafenib or lenvatinib, or choosing among regorafenib or cabozantinib, already approved in the refractory setting...Despite the tissue remaining a preferred source, biomarkers discovery could take advantage of liquid biopsy to overcome the matter of tissue availability and track tumor changes. Lastly, tumor genetic phenotypes, tumor microenvironment features, gut microbiome, and markers of immune response and systemic inflammation are all potential emergent predictors of response to ICIs, pending validation in the clinical setting.

Imatinib mesylate revolutionized the management of advanced/metastatic GIST, and remains the standard first-line therapy in this setting. Upon development of secondary resistance, sunitinib and regorafenib are used as subsequent treatments, although clinical benefit is often non-durable...Ripretinib is safe and effective therapy for the fourth-line setting in advanced/ metastatic GIST. Future studies should evaluate combination schedules and the identification of markers predictive of benefit from ripretinib.

KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

P2; N=120 --> 84 | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

P2, N=48, Recruiting, University of Miami | Trial completion date: Jan 2028 --> Apr 2028 | Initiation date: Jan 2023 --> Apr 2023 | Trial primary completion date: Jan 2026 --> Apr 2026

P2, N=40, Recruiting, Asan Medical Center | Unknown status --> Recruiting | Trial completion date: Aug 2021 --> Nov 2023 | Trial primary completion date: Aug 2021 --> Nov 2023

P1/2, N=39, Completed, Asan Medical Center | Recruiting --> Completed

Finally, we proposed five KG-guided repurposable drug molecules (imatinib, regorafenib, pazopanib, teniposide, and dexrazoxane) for TNBC through network pharmacology and molecular docking analyses. These drug molecules also showed significant binding performance with some cancer-related PTM-sites (phosphorylation, succinylation, and ubiquitination) of top-ranked four key proteins (EGFR, AURKB, BIRC5, and TOP2A). Therefore, the findings of this computational study may play a vital role in early diagnosis and therapies against TNBC by wet-lab validation.

The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment.

This activity is supported by educational grants from Bayer HealthCare Pharmaceuticals, Exelixis Inc, Lilly, Natera Inc, and Seagen Inc. Key data informing the rational incorporation of pembrolizumab, nivolumab and nivolumab/ipilimumab for microsatellite instability-high/mismatch repair-deficient mCRC Early results with and ongoing investigation of immune checkpoint inhibitors in combination with other systemic approaches (eg, chemotherapy, targeted therapy) for MSI-H/dMMR advanced CRC Biologic rationale for the investigation of immune checkpoint inhibition for microsatellite-stable (MSS) mCRC Clinical activity and safety observed with cabozantinib in combination with anti-PD-1/PD-L1 antibodies among patients with MSS mCRC in early-phase trials (eg, COSMIC-021 cohort 16, CAMILLA cohort 2) Pharmacologic and pharmacodynamic comparison of cabozantinib and XL092 Design, eligibility and efficacy and safety endpoints for the Phase III STELLAR-303 trial comparing XL092/atezolizumab to regorafenib for relapsed/refractory (R/R) MSS mCRC Available data with and ongoing investigation of other immune checkpoint inhibitor-based strategies (eg, lenvatinib/pembrolizumab, regorafenib/pembrolizumab) for MSS mCRC Available data with and ongoing investigation of other immune checkpoint inhibitor-based strategies (eg, lenvatinib/pembrolizumab, regorafenib/pembrolizumab) for patients with MSS mCRC