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DRUG:

Lonsurf (trifluridine/tipiracil)

i
Other names: TAS102, TAS-102, S 95005, FTD/TPI, TAS-102/S-95005, S-95005, S95005, TAS 102, S 95005/TAS-102, T15, T20, T15/T20
Company:
Otsuka, Servier, TTY Biopharm
Drug class:
Thymidine phosphorylase inhibitor
15h
FOG-001-101: FOG-001 in Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=480, Recruiting, Parabilis Medicines, Inc. | N=245 --> 480
Enrollment change • Metastases
|
MSI (Microsatellite instability) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
Opdivo (nivolumab) • Avastin (bevacizumab) • 5-fluorouracil • oxaliplatin • Lonsurf (trifluridine/tipiracil) • leucovorin calcium • FOG-001
6d
Trial initiation date • Metastases
|
Opdivo (nivolumab) • Avastin (bevacizumab) • Herceptin (trastuzumab) • 5-fluorouracil • Vectibix (panitumumab) • capecitabine • oxaliplatin • Lonsurf (trifluridine/tipiracil)
7d
CardioSwitch: Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study (clinicaltrials.gov)
P=N/A, N=200, Enrolling by invitation, Helsinki University Central Hospital | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2020 --> Dec 2027
Trial completion date • Trial primary completion date
|
5-fluorouracil • capecitabine • Lonsurf (trifluridine/tipiracil) • Teysuno (gimeracil/oteracil/tegafur)
28d
New P2 trial • Combination therapy • Metastases
|
Avastin (bevacizumab) • Lonsurf (trifluridine/tipiracil) • Vyrologix (leronlimab)
29d
Enrollment open • Adverse events • Metastases
|
Avastin (bevacizumab) • Lonsurf (trifluridine/tipiracil) • telisotuzumab adizutecan (ABBV-400)
30d
Late-line options for patients with metastatic colorectal cancer: a review and evidence-based algorithm. (PubMed, Nat Rev Clin Oncol)
Over the past decade, regorafenib and trifluridine-tipiracil were the only available drugs and often provided limited clinical benefit compared to best supportive care. Results from subsequent practice-changing trials opened several novel therapeutic avenues, both for unselected patients (such as trifluridine-tipiracil plus bevacizumab or fruquintinib) and for subgroups defined by the presence of actionable alterations in their tumours (such as HER2-targeted therapies or KRASG12C inhibitors) or with no acquired mechanisms of resistance to the previously received targeted agents in circulating tumour DNA (such as retreatment with anti-EGFR antibodies). In this Review, we provide a comprehensive overview of advances in the field over the past few years and offer a practical perspective on translation of the most relevant results into the daily management of patients with metastatic colorectal cancer using an evidence-based algorithm. Finally, we discuss some of the most appealing ongoing areas of research and highlight approaches with the potential to further expand the therapeutic armamentarium.
Review • Journal • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
Avastin (bevacizumab) • Stivarga (regorafenib) • Fruzaqla (fruquintinib) • Lonsurf (trifluridine/tipiracil)
1m
TAS-102 and Oxaliplatin for the Treatment of Refractory Stage IV Colon Cancer (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Rutgers, The State University of New Jersey | Trial completion date: Mar 2024 --> Mar 2026
Trial completion date • Combination therapy • Metastases
|
RAS mutation • RAS wild-type
|
oxaliplatin • Lonsurf (trifluridine/tipiracil)
1m
Phase I/II study of trifluridine/tipiracil plus XB2001 versus trifluridine/tipiracil in metastatic colorectal cancer. (PubMed, Future Oncol)
We aim to assess the addition of XB2001 (anti-IL-1 alpha monoclonal antibody) plus trifluridine/tipiracil-bevacizumab in mCRC refractory to standard chemotherapy. This multicenter, randomized, double blind, non-comparative Phase I-II study (ClinicalTrials.gov NCT05201352) will assess the efficacy and safety of trifluridine/tipiracil-bevacizumab and XB2001 in patients with mCRC previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, 5-FU, antiangiogenic and/or anti-EGFR if indicated...Primary end point of Phase II is the efficacy of trifluridine/tipiracil-bevacizumab + XB2001 in term of 6-month overall survival. Ancillary analysis will be performed.
P1/2 data • Journal • Metastases
|
IL1A (Interleukin 1, alpha)
|
Avastin (bevacizumab) • 5-fluorouracil • oxaliplatin • irinotecan • Lonsurf (trifluridine/tipiracil)
1m
New P4 trial
|
oxaliplatin • Lonsurf (trifluridine/tipiracil)
1m
Efficacy and safety of trifluridine/tipiracil combined with fufuquitinib versus trifluridine/tipiracil and fufuquitinib for third-line treatment of unresectable metastatic colorectal cancer. (ChiCTR2400088929)
P4, N=200, Not yet recruiting, The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University
New P4 trial • Metastases
|
Lonsurf (trifluridine/tipiracil)
1m
New P1/2 trial • Combination therapy • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
PD-L1 expression
|
Tyvyt (sintilimab) • Fruzaqla (fruquintinib) • Lonsurf (trifluridine/tipiracil)
1m
New P2 trial • Metastases
|
paclitaxel • Cyramza (ramucirumab) • irinotecan • Lonsurf (trifluridine/tipiracil) • bemarituzumab (AMG 552)
2ms
Trial completion date • Metastases
|
Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
2ms
Trial completion date • Metastases
|
Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
2ms
Trial completion • Combination therapy • Metastases
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)
|
BRAF V600E • MSI-H/dMMR • BRAF V600 • KRAS wild-type • RAS wild-type • NRAS wild-type
|
Keytruda (pembrolizumab) • Lenvima (lenvatinib) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
2ms
Tumor-associated macrophages confer resistance to chemotherapy (Trifluridine/Tipiracil) in digestive cancers by overexpressing Thymidine Phosphorylase. (PubMed, Cancer Lett)
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.
Journal
|
TYMP (Thymidine Phosphorylase)
|
5-fluorouracil • Lonsurf (trifluridine/tipiracil)
2ms
TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice. (PubMed, Front Oncol)
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.
Journal • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • RAS mutation • KRAS G12
|
Avastin (bevacizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
3ms
Predictive and Prognostic Role of Systemic Immune-Inflammation Index (SII) in Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil. (PubMed, Biomedicines)
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.
Clinical • Journal • Metastases
|
CEACAM5 (CEA Cell Adhesion Molecule 5)
|
Lonsurf (trifluridine/tipiracil)
3ms
FIERCE: TAS-102 with Concurrent Radiation for the Treatment of Untreated Resectable Stage II-III Rectal Cancer (clinicaltrials.gov)
P1, N=19, Active, not recruiting, OHSU Knight Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Sep 2024
Enrollment closed • Trial primary completion date
|
Lonsurf (trifluridine/tipiracil)
3ms
Clinical Trial Data Review of the Combination FTD/TPI + Bevacizumab in the Treatment Landscape of Unresectable Metastatic Colorectal Cancer. (PubMed, Curr Treat Options Oncol)
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.
Review • Journal • Metastases
|
EGFR (Epidermal growth factor receptor)
|
RAS mutation
|
Avastin (bevacizumab) • 5-fluorouracil • capecitabine • Lonsurf (trifluridine/tipiracil)
3ms
TAS-102, Irinotecan, and Bevacizumab for the Treatment of Pre-treated Metastatic or Unresectable Colorectal Cancer, the TABAsCO Study (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date
|
Avastin (bevacizumab) • irinotecan • Lonsurf (trifluridine/tipiracil)
3ms
New P2 trial
|
Avastin (bevacizumab) • Lonsurf (trifluridine/tipiracil) • Melblez Kit (melphalan hepatic delivery system)
3ms
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
MSI-H/dMMR • BRAF mutation • HER-2 amplification • PIK3CA mutation • BRAF V600
|
Guardant360® CDx
|
Tukysa (tucatinib) • Lonsurf (trifluridine/tipiracil) • Trazimera (trastuzumab-qyyp)
3ms
TriComB: Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients. (clinicaltrials.gov)
P1/2, N=48, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Recruiting --> Active, not recruiting
Enrollment closed
|
Avastin (bevacizumab) • capecitabine • Lonsurf (trifluridine/tipiracil)
3ms
TRIFLUOX-DP: Safety of Trifluridine/Tipiracil in Patients With Dihydropyrimidine Dehydrogenase Deficiency Diagnosed With Metastatic Colorectal or Gastroesophageal Cancer (clinicaltrials.gov)
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
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
|
Opdivo (nivolumab) • Avastin (bevacizumab) • Herceptin (trastuzumab) • 5-fluorouracil • Vectibix (panitumumab) • capecitabine • oxaliplatin • Lonsurf (trifluridine/tipiracil)
3ms
Unraveling the Role of PCDH9 in Breast Cancer and Identifying Therapeutic Strategies for PCDH9-Deficient Tumors. (PubMed, Breast Cancer (Dove Med Press))
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.
Journal
|
CDH23 (Cadherin Related 23)
|
Lonsurf (trifluridine/tipiracil)
4ms
Exploratory Study Identifies Matrix Metalloproteinase-14 and -9 as Potential Biomarkers of Regorafenib Efficacy in Metastatic Colorectal Cancer. (PubMed, Cancers (Basel))
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.
Journal • Metastases
|
MMP9 (Matrix metallopeptidase 9) • MMP14 (Matrix Metallopeptidase 14)
|
Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
4ms
TAS 102 in Combination With Ramucirumab in Advanced, Refractory Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (clinicaltrials.gov)
P2, N=23, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed
Trial completion • Combination therapy • Metastases
|
Cyramza (ramucirumab) • Lonsurf (trifluridine/tipiracil)
4ms
ACCRU-GI-1618: Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer (clinicaltrials.gov)
P2, N=102, Completed, Academic and Community Cancer Research United | Trial completion date: Apr 2024 --> Jul 2024 | Active, not recruiting --> Completed
Trial completion • Trial completion date • Metastases
|
KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
Ibrance (palbociclib) • Mektovi (binimetinib) • Lonsurf (trifluridine/tipiracil)
4ms
New P2 trial • Metastases
|
Avastin (bevacizumab) • Lonsurf (trifluridine/tipiracil)
4ms
RAMTAS: RAMucirumab in Combination Wth TAS102 vs. TAS102 Alone in Chemotherapy Refractory Metastatic Colorectal Cancer Patients (clinicaltrials.gov)
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
Trial completion • Trial primary completion date • Combination therapy • Metastases
|
BRAF (B-raf proto-oncogene)
|
Cyramza (ramucirumab) • Lonsurf (trifluridine/tipiracil)
5ms
Budget impact analysis of introducing fruquintinib for metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy and biologics in the United States from the payer perspective. (PubMed, J Med Econ)
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.
Journal • HEOR • Metastases
|
EGFR (Epidermal growth factor receptor)
|
Avastin (bevacizumab) • Stivarga (regorafenib) • oxaliplatin • irinotecan • Fruzaqla (fruquintinib) • Lonsurf (trifluridine/tipiracil)
5ms
Trial primary completion date • Enrollment change • Trial withdrawal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
Guardant360® CDx
|
Tukysa (tucatinib) • Lonsurf (trifluridine/tipiracil) • Trazimera (trastuzumab-qyyp)
5ms
New P2 trial • Mismatch repair • Metastases
|
Keytruda (pembrolizumab) • Avastin (bevacizumab) • Lonsurf (trifluridine/tipiracil)
5ms
Single arm, single center, exploratory clinical study of trifluridine and tipiracil hydrochloride tablets(TAS-102) combined with Oxaliplatin and Sintilimab in the first-line treatment of advanced unresectable gastric cancer (ChiCTR2400080940)
P=N/A, N=20, Not yet recruiting, Renji Hospital, Shanghai Jiaotong University School of Medicine; Renji Hospital, Shanghai Jiaotong University School of Medicine
New trial
|
HER-2 (Human epidermal growth factor receptor 2)
|
Tyvyt (sintilimab) • oxaliplatin • Lonsurf (trifluridine/tipiracil)
5ms
Trial completion date • Metastases
|
Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
5ms
New trial • Metastases
|
oxaliplatin • irinotecan • Lonsurf (trifluridine/tipiracil)
6ms
A case of treatment-resistant advanced gastric cancer with FGFR2 gene alteration successfully treated with pemigatinib. (PubMed)
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.
Journal • PD(L)-1 Biomarker • Metastases
|
FoundationOne® Liquid CDx
|
Opdivo (nivolumab) • cisplatin • docetaxel • Cyramza (ramucirumab) • irinotecan • Pemazyre (pemigatinib) • Lonsurf (trifluridine/tipiracil) • Teysuno (gimeracil/oteracil/tegafur)
6ms
New P2 trial • Metastases
|
Lonsurf (trifluridine/tipiracil)
6ms
Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status. (PubMed, Oncotarget)
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.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
|
Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
6ms
Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis. (PubMed, Eur J Cancer)
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.
Retrospective data • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)