Stivarga (regorafenib) / Amgen, Bayer - LARVOL DELTA

SED-RO-ICC: Second-line Regimen Combined With Radiotherapy Versus Without Radiotherapy in Patients With Locally Advanced/Oligometastatic ICC After Failure of First-line Treatment：an Open-label, Randomized, Controlled Phase II Clinical Study (clinicaltrials.gov) - P2 | N=76 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P2 trial • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Stivarga: Expiry of patents related to active ingredients in Japan in 2026 (Bayer AG) - Annual Report 2024: Expiry of patents related to active ingredients in Germany, France, Italy, Switzerland, Spain and UK in 2028; Expiry of patents related to active ingredients in US in 2031

Patent • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hepatocellular Cancer • Liver Cancer • Oncology • Rectal Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Effects of first‑line therapies in patients with locally advanced gastrointestinal stromal tumors with KIT and PDGFRα gene mutations: A single‑center study. (PubMed, Oncol Lett) - "Treatment regimens included imatinib, with subsequent therapies, such as sunitinib and regorafenib, administered upon imatinib failure. The present study elucidated the effects of first-line therapy on LAGISTs with genetic mutations, underscoring the effectiveness of imatinib treatment and the value of continual patient monitoring. Additional studies with long-term follow-up are required to evaluate treatment outcomes."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Gene Therapies • Oncology • Sarcoma • PDGFRA

Cost-effectiveness analysis of regorafenib dose optimization for refractory metastatic colorectal cancer. (PubMed, J Med Econ) - "BackgroundNew regimens have emerged as third-line or later therapies for metastatic colorectal cancer (mCRC), including regorafenib dose optimization (ReDO), trifluridine/tipiracil and bevacizumab (TAS-BEV) combination therapy, and fruquintinib. Sensitivity and scenario analyses were conducted to address these limitations.ConclusionReDO was cost-effective compared with TAS-BEV from the US payer's perspective despite a higher QALY gain associated with TAS-BEV. ReDO was dominant over fruquintinib, consistently having a higher QALY gain and lower cost."

HEOR • Journal • Colorectal Cancer • Oncology • Solid Tumor

TGRX-3544 is a highly potent and mutant-selective degrader of oncogenic KIT with oral activity (AACR 2025) - "The cellular activity of TGRX-3544 against the E11, E17 and E11/E17 mutants was superior to that of all the currently approved KIT inhibitors imatinib, sunitinib, regorafenib, avapritinib and ripretinib. In summary, we have developed a highly mutant-selective, event-driven, scaffold-eliminating KIT degrader with superior cellular potency and in vivo oral activity. The balanced preclinical profile of TGRX-3544 supports its further clinical investigation in KIT-driven malignancies such as GIST and SM."

Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • ABL1 • BCR • EGFR • FLT3 • PDGFRA • STAT5

Real-world evidence of fruquintinib (Fruq) efficacy after regorafenib (Rego) and trifluridine–tipiracil (TAS-102) in refractory metastatic colorectal cancer (mCRC). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor

Evaluating the efficacy of fruquintinib versus regorafenib and trifluridine/tipiracil in treating advanced metastatic colorectal cancer: A match-adjusted indirect comparison. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

EMB-01, an EGFR/cMET bispecific antibody, in metastatic colorectal cancer: Results from an international phase Ib/II study (AACR 2025) - P1/2 | "The median lines of prior systemic therapies were 3 (range 1-11), with 66.7% having received prior anti-EGFR therapy, 79.2% anti-VEGF therapy, and 27.1% fruquintinib, regorafenib, or trifluridine/tipiracil (TAS-102). EMB-01 demonstrated promising efficacy in heavily pretreated mCRC, including those with prior progression on anti-EGFR, with an acceptable safety profile at 1600 mg, warranting further investigation in larger cohorts.References: 1. Ren et al. Cancer Res 2020; 80(16 Suppl): Abstract 528."

Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor

Sex differences in toxicities among patients receiving regorafenib or trifluridine/tipiracil for refractory metastatic colorectal cancer: A subgroup analysis from the multicenter retrospective ReTrITA study. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Metastases • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor

Baseline biomarker analyses of patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) from the phase 3 CodeBreaK 300 study (AACR 2025) - P3 | "In CodeBreaK 300 (NCT05198934), sotorasib (soto) 960 mg plus panitumumab (pani) showed significant improvement in progression-free survival (PFS) compared with trifluridine/tipiracil (T/T) or regorafenib (rego) (hazard ratio, 0.48 [95% CI, 0.30-0.78]; P = 0.005) in patients with chemorefractory KRAS G12C-mutated mCRC. Genetic alteration rates in CodeBreaK 300 were similar across all treatment arms and comparable to those observed in CodeBreaK 100 and 101 and KRAS G12C+ cases in AACR Genie BPC v1.1. Soto 960 mg plus pani demonstrated consistent clinical benefits compared with T/T or rego across various molecularly defined subgroups. While no additional strong biomarkers associated with response were identified, this study supported the potential association of ARID1A alterations with shorter PFS as previously reported in CodeBreaK 101."

Biomarker • Clinical • Metastases • P3 data • Colorectal Cancer • Oncology • Solid Tumor • ARID1A • DNMT3A • KRAS • PIK3CA • SMAD4 • TET2 • TGFB1 • TP53

Overall survival based on sequencing of fruquintinib, regorafenib, and TAS-102 with or without bevacizumab in treatment-refractory metastatic colorectal cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

Fibroblast growth factor receptor (FGFR) inhibition demonstrates anti-tumor activity in succinate dehydrogenase deficient gastrointestinal stromal tumor (SDHd GIST) (AACR 2025) - P2 | " FGFRi rogaratinib (R) and pemigatinib (P) were evaluated separately in SDHd GIST PDX (PG-20) and compared to vehicle, sunitinib, and regorafenib. FGFR inhibition demonstrates notable activity in SDHd GIST. Preclinical data suggest this is a class effect of drugs which inhibit FGFRs. This work supports targeting aberrant FGFR signaling arising from epigenetic alterations in pts with SDHd GIST."

Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • FGF3 • FGF4 • FGFR • FGFR1 • SDHA • SDHC • SDHD

Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Results of a multicenter, phase II trial (TRAP) (AACR 2025) - P2 | "TRAP (NCT04483219) aims to explore the efficacy and safety of antiangiogenic TKIs combined with PD-1 blockade in TKI-responsive MSS/pMMR mCRC pts refractory to standard treatment. Eligible pts were given 1 cycle of TKIs (fruquintinib 5mg or regorafenib 120mg, d1-21, q4w) and grouped by tumor response according to RECIST v1.1: arm A: reduction of target lesion to CR, PR or shrunken SD, or cavitation in metastatic lung lesions, or decrease in the density of liver metastatic target lesions ≥15%; arm B: enlarged SD; arm C: PD...Pts in arm A then received TKIs plus anti-PD-1 antibody (toripalimab 240mg, or sintilimab 200mg, i.v.gtt, q3w, until PD or up to 2 years), pts in arm B continued with TKIs until PD... TKIs combined with PD-1 blockade has shown encouraging efficacy with acceptable toxicities in MSS/pMMR mCRC pts responsive to TKI treatment. The regimen could be a preferred approach in pretreated MSS/pMMR mCRC."

Clinical • IO biomarker • Metastases • P2 data • pMMR • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Predictive biomarkers and immune dynamics in MSS metastatic colorectal cancer treated with regorafenib, ipilimumab, and nivolumab (AACR 2025) - "The RIN regimen can reshape the immunological landscape of MSS mCRC by modulating the TME and systemic immunity. Distinct immune profiles between responders and non-responders, especially in patients with liver metastases, highlight the importance of predictive biomarkers for personalized therapy. Addressing immune senescence and metabolic dysregulation may be key to overcoming resistance in this challenging patient population."

Biomarker • IO biomarker • Metastases • Colorectal Cancer • Oncology • Solid Tumor • CD8 • STING

Personalized treatment for hepatocellular carcinoma (HCC) patients (AACR 2025) - "Anticancer agents such as sorafenib and regorafenib were found to increase drug resistance in 3D cell culture models of HCC...Drug resistance profiles varied among HCC patients, with some demonstrating sensitivity to sorafenib and lapatinib, while others showed resistance to tivantinib...In particular, one individualized HCC patient showed the best drug response to lenvatinib and sunitinib. Furthermore, our prediction model revealed that lapatinib exhibited higher drug resistance, mirroring patterns observed in tumor cells associated with regulatory T cells, tissue-resident memory T cells (TRM), and tumor-associated macrophages (TAMs). These findings suggest that our approach offers a promising framework for predicting drug responses in HCC, supporting its application in personalized medicine."

Clinical • Hepatocellular Cancer • Oncology • Solid Tumor

Glioblastoma in Appalachia: A retrospective analysis (AACR 2025) - "In the 2nd line setting, no significant differences in PFS or OS were observed between bevacizumab+lomustine (n=7), bevacizumab+surgery (n=9), bevacizumab +temozolomide (n=8), and bevacizumab (n=41)...In the 2nd line targeted therapy setting, no significant differences in PFS or OS were observed between osimertinib (n=2), pembrolizumab (n=2), regorafenib (n=3), and abemaciclib (n=3). Our preliminary data suggests that mortality related to GBM in Appalachia follows the national trends. It is prudent to conduct rural-specific studies to understand the phenotypic, genotypic, and demographic characteristics."

Retrospective data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Updated efficacy and safety data for cadonilimab plus regorafenib as second-line or later therapy in advanced hepatocellular carcinoma (aHCC) (AACR 2025) - P1 | "The combination of Cadonilimab and Regorafenib demonstrated a favorable safety profile and manageable toxicity in aHCC, including heavily pretreated patients. Although the ORR was modest, the DCR and mPFS indicate potential clinical benefit. This finding underscores the pressing need to develop new therapeutic options for patients with aHCC who have exhausted second-line or later treatments and face limited alternatives."

Clinical • Metastases • Hepatocellular Cancer • Oncology • Solid Tumor

Phase Ib/II open-label, randomized study of atezolizumab + regorafenib + AB928 or atezolizumab + regorafenib vs regorafenib for patients with microsatellite-stable, refractory metastatic colorectal cancer in MORPHEUS-CRC (AACR 2025) - P1/2 | "Atezo + rego ± AB928 did not have sufficient clinical activity to merit further evaluation in an unselected mCRC population. Consistent with other reports of PD-(L)1-directed immunotherapy in mCRC, durable responses were observed in pts without liver metastases.EfficacyAtezo + rego + AB298(n=15)bAtezo + rego(n=15)aRego (control)(n=19)a,cORR, n (%)1 (6.7)1 (6.7)095% CI(0.2, 32.0)(0.2, 32.0)(0.0, 17.7)CR, n (%)00095% CI(0.0, 21.8)(0.0, 21.8)(0.0, 17.7)PR, n (%)1 (6.7)1 (6.7)095% CI(0.2, 32.0)(0.2, 32.0)(0.00, 17.7)SD, n (%)8 (53.3)5 (33.3)12 (63.2)95% CI(26.6, 78.7)(11.8, 61.6)(38.4, 83.7)PD, n (%)4 (26.7)7 (46.7)5 (26.3)95% CI(7.8, 55.1)(21.3, 73.4)(9.2, 51.2)DCR, n (%)6 (40.0)2 (13.3)3 (15.8)95% CI(16.3, 67.7)(1.7, 40.5)(3.4, 39.6)Median PFS (investigator-assessed RECIST 1.1), mo4.61.82.895% CI(2.6, 5.8)(1.4, 3.0)(2.2, 3.0)HR vs rego (95% CI)0.8 (0.4, 1.6)1.7 (0.8, 3.6)Median OS, mo8.711.010.295% CI(6.6, 14.6)(5.3, 16.7)(4.4, 12.3)HR vs rego (95% CI)0.9 (0.4,..."

Clinical • IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor • KRAS

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (clinicaltrials.gov) - P2 | N=4200 | Recruiting | Sponsor: American Society of Clinical Oncology | Trial completion date: Jun 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Tumor mutational burden • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BRAF

A multi-cohort study of treatment regimens for metastatic colorectal cancer (mCRC): Subgroup analysis of sequential therapy between fruquintinib and regorafenib (AACR 2025) - "Within the mono subgroup, the mOS for the Fru-Reg (mono) group was 19.05 months versus 15.79 months for the Reg-Fru (mono) group.ConclusionThis study provides valuable insights into the comparative effectiveness of sequential Fru and Reg treatment regimens in pts with mCRC. The results showed that in the overall patient population and mono subgroup, pts with Fru sequential Reg had a trend of benefit in mOS compared with pts with Reg sequential Fru opposite, but the difference was not statistically significant, we will continue to increase the sample size of the enrolled pts to further validate this finding."

Metastases • Colorectal Cancer • Oncology • Solid Tumor • CSF1R • FLT1

3D-bioprinted cancer models for prediction of drug response driven by H&E-based AI algorithm (AACR 2025) - "Interestingly, ENLIGHT-DP predicted that the patient would respond to regorafenib, a suggestion corroborated by our 3D model. Following this promising outcome, the patient received it as compassionate use, resulting in an immediate partial response lasting for 6 months so far. These unique 3D models have the potential to facilitate target discovery and drug development, as well as to serve as a reliable system for precision medicine."

IO biomarker • Preclinical • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

International clinical research programme to improve outcomes in newly diagnosed Ewing sarcoma – Trial 1 (ANZCTR) - P3 | N=900 | Recruiting | Sponsor: University of Birmingham | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2024

Enrollment open • Trial initiation date • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • EWSR1

Combination of inhibitors of RAD51 and FLT-3 and other tyrosine kinase inhibitors synergistically inhibits proliferation of cultured human leukemia cell lines (AACR 2025) - "IBR2, an inhibitor of the DNA repair protein RAD51, was previously demonstrated to enhance the antiproliferative activity of imatinib against the CML blastoid cell line K562 (EMBO Mol Med 5: 353-365, 2013...In our studies, IBR2 enhanced the antiproliferative activity of regorafenib, an inhibitor of multiple tyrosine kinases, in a concentration-dependent manner by up to 80% against K562 cells (J Pharmacol Expt Ther, 364: 46-54, 2018...These findings suggest that: (1) the combination of quizartinib and a RAD51-inhibitor could be a useful treatment against FLT-3-wt AML; (2) quizartinib and gilteritinib may not act in exactly the same way against the FLT-3 target or other related targets; (3) novel combinations of a RAD51 inhibitor with non-traditional treatments for CML may provide a potential improvement in outcome for CML blast crisis; (4) RAD51 inhibitors may be active as monotherapy in myeloid leukemias. The combination of JKYN-1-mesylate with FLT-3 inhibitors under..."

Preclinical • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • RAD51

Resistance to VEGFR inhibitors converges from molecular diversity in angiosarcoma cells (AACR 2025) - "However, therapeutic antibodies, such as bevacizumab (Avastin), and chemical inhibitors targeting VEGF pathways have shown limited clinical benefits in angiosarcomas...Then, we examined cellular response to VEGFR2 (Regorafenib, Sorafenib) and Tie2 inhibitors (Rebastinib, Pexmetinib) using cell growth inhibition assays...Furthermore, our results suggest angiosarcoma cells establish a functional convergence that potentiates the signaling activation of VEGF and Tie2 pathways, despite their molecular divergence. Our ongoing work aims to explore the molecular mechanisms promoting resistance to VEGF and Tie2 inhibitors."

Angiosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD31 • PECAM1

CCGLC-001: Combined HAIC, TKI/anti-VEGF and ICIs As Conversion Therapy for Unresectable Hepatocellular Carcinoma (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Ze-yang Ding, MD | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Apr 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor