Lonsurf (trifluridine/tipiracil)

P4, N=30, Not yet recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

P4, N=200, Not yet recruiting, The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University

P1/2, N=62, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=126, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P3, N=94, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Feb 2025

P3, N=505, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Feb 2025

P3, N=480, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Trifluridine combined with tipiracil, a specific thymidine phosphorylase inhibitor, in TAS-102 has recently emerged as a potential alternative in the face of primary or secondary chemoresistance to 5-fluorouracil. To study the importance of macrophages in chemoresistance to trifluridine, we developed a humanized mouse model with tumor-implanted human macrophages and demonstrated their important role in treatment resistance to pyrimidine analogs. Additionally, our findings revealed that macrophages represent a significant source of thymidine phosphorylase expression, comprising over 40% of the expressing cells, in human colorectal cancer, thereby contributing to chemoresistance.

The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.

Favorable prognostic factors revealed in the multivariate analysis of overall survival (OS) were: <3 prior lines of treatment (p = 0.02), good to moderate histological differentiation (p = 0.0003), CEA < 5 ng/L (p = 0.0227) and SII ≤ 550 (p = 0.0001). Our study indicated that pre-treatment SII may be clinically useful for selecting likely responder patients and assessing the prognosis for mCRC patients treated with TT.

P1, N=19, Active, not recruiting, OHSU Knight Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Sep 2024

Recommended first and second line treatments for unresectable metastatic colorectal cancer (mCRC) include fluorouracil-based chemotherapy, anti-vascular endothelial growth factor (VEGF)-based therapy, and anti-epidermal growth factor receptor-targeted therapies...Capecitabine (CAP) + BEV is recommended in these patients...FTD/TPI + BEV offers a possible first line alternative in patients for whom CAP + BEV is an unsuitable treatment. This narrative review explores and summarizes the clinical trial data on FTD/TPI + BEV.

P3, N=460, Not yet recruiting, AbbVie

P2, N=42, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2023 --> Jul 2024

P2, N=90, Not yet recruiting, Delcath Systems Inc.

P2; Trial completion date: May 2029 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

P1/2, N=48, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Recruiting --> Active, not recruiting

P2, N=73, Not yet recruiting, UNICANCER | Trial completion date: Jun 2028 --> Oct 2028 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2026 --> Oct 2026

In summary, our study identified PCDH9 as a tumor suppressor in breast cancer and highlighted TAS-102 as a potential therapeutic option for tumors with low PCDH9 expression or deficiency. The specific interaction between TAS-102 and PCDH9 warrants further exploration, providing deeper insights into its mode of action in treating PCDH9-deficient breast cancer.

These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI.

P2, N=23, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

P2, N=102, Completed, Academic and Community Cancer Research United | Trial completion date: Apr 2024 --> Jul 2024 | Active, not recruiting --> Completed

P2, N=40, Recruiting, UMC Utrecht

P3, N=430, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Trial primary completion date: Dec 2023 --> Jul 2024 | Active, not recruiting --> Completed

A budget impact model was developed to compare two scenarios: a reference scenario in which patients received regorafenib, trifluridine/tipiracil, or trifluridine/tipiracil with bevacizumab and an alternative scenario in which patients received reference scenario treatments or fruquintinib. PMPM costs from the Medicare perspective were greater than the base-case (commercial) ($0.17 vs. $0.07) due to higher incidence of CRC in that population. Fruquintinib is associated with a low budget impact for payers based on proposed thresholds in the US.

P2; N=30 --> 0 | Not yet recruiting --> Withdrawn | Trial primary completion date: May 2024 --> May 2025

P2, N=36, Not yet recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

P=N/A, N=20, Not yet recruiting, Renji Hospital, Shanghai Jiaotong University School of Medicine; Renji Hospital, Shanghai Jiaotong University School of Medicine

P3, N=94, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jul 2025 --> Nov 2025

P=N/A, N=110, Recruiting, Chang Gung Memorial Hospital

The patient (male, 52 years old) was diagnosed with advanced gastric cancer (cStage IV, cT4aN3M1 [LYM], por, HER2 0, microsatellite stable) and received docetaxel + cisplatin + S-1 (7 cycles), irinotecan + ramucirumab (11 cycles), and nivolumab (3 cycles), but experienced progressive disease (PD)...After three cycles of TAS-102, the patient experienced PD and provided consent for the off-label use of pemigatinib...To the best of our knowledge, this is the first reported case of pemigatinib therapy employed in a patient with advanced gastric cancer exhibiting FGFR2 gene alterations. This case could serve as a notable example of tumor-agnostic therapy to broaden treatment options for gastric cancer patients with rare genetic alterations.

P2, N=200, Recruiting, First Affiliated Hospital of Wenzhou Medical University

TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.

LM is a poor prognostic factor for mCRC increasing from 1 L to ≥ 3 L except for patients in 1 L and 2 L receiving CT+anti-EGFR. These data justify using LM as a stratification factor in future trials for patients with unresectable mCRC.

P2, N=7, Completed, AHS Cancer Control Alberta | Not yet recruiting --> Completed | N=20 --> 7 | Trial completion date: Aug 2027 --> Jul 2023

P1, N=45, Recruiting, Roswell Park Cancer Institute | Trial primary completion date: Jul 2024 --> Sep 2026

P=N/A, N=818, Active, not recruiting, Bayer | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2024 --> Oct 2024

OS1 was used to measure the time from disease progression after TAS-102 and regorafenib treatment to death, while OS2 was used to measure the time from TAS-102 or regorafenib treatment to death. NGS analysis revealed that GNAS and KRAS alterations were associated with a worse treatment response and prolonged survival, respectively. In conclusion, a moderate-dose salvage lenvatinib-based regimen demonstrated promising clinical activity and tolerability in treating refractory mCRC.

In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed.

P2; N=84 --> 12

P2; Recruiting --> Suspended

P1, N=45, Recruiting, Roswell Park Cancer Institute | Trial completion date: Feb 2026 --> Apr 2027 | Trial primary completion date: Jun 2025 --> Jul 2024