Lonsurf (trifluridine/tipiracil)

P3, N=450, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

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

P2, N=28, Active, not recruiting, The University of Hong Kong | Recruiting --> Active, not recruiting | Trial completion date: Nov 2023 --> Dec 2024 | Trial primary completion date: May 2023 --> Mar 2024

P2, N=35, Active, not recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P1/2, N=95, Completed, UCB Biopharma SRL | Active, not recruiting --> Completed

P3, N=450, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting

P1, N=29, Terminated, Elevar Therapeutics | Phase classification: P1b/2 --> P1 | Completed --> Terminated; Phase 2 portion of the study was not performed due to redirection of the rivoceranib development plan by the Sponsor.

This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings.

P1/2, N=26, Recruiting, Wangxia LV

Our data demonstrate that RAS mutations do not affect outcome in rego-treated patients as well as TFD/TPI-treated patients. Nevertheless, a trend toward a higher efficacy of rego in RAS-mutated (in particular codon 12, rare RAS mutations, and G12D) patients has been recorded. The rego-TFD/TPI sequence seems to be superior to the reverse sequence in patients carrying an RAS codon 12 mutation, although the impact of other factors as disease burden or performance status cannot be excluded.

Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival. ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

P3, N=450, Not yet recruiting, Merck Sharp & Dohme LLC

"BACKGROUND: Systemic therapies such as fruquintinib, regorafenib, and trifluridine/tipiracil (T/T) have demon- strated survival benefits vs best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) pre- viously treated with oxaliplatin- and irinotecan-based chemotherapy (OIC)...OBJECTIVE: To compare the AE management costs of fruquin- tinib, regorafenib, T/T and T/T+bevacizumab (T/T+bev) for mCRC previously treated with OIC, from US Commercial and Medicare payer perspectives... Based on the cost-consequence model results, fruquintinib was associated with lower AE manage- ment costs compared with regorafenib, T/T, and T/T+bev for patients with mCRC previously treated with OIC, which should be considered in treatment and formulary decision- making."

P2, N=23, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2024 --> Jul 2024

P1, N=26, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023

P3, N=589, Recruiting, AstraZeneca

Fruquintinib, a tyrosine kinase inhibitor, has been shown to be effective in heavily pretreated mCRC progressing to trifluridine-tipiracil (FTD/TPI) or regorafenib or both...These results led to FDA approval of fruquintinib for pretreated mCRC patients who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy...However, an optimal sequence of treatments is yet to be defined. In this review, we propose an algorithm for later lines of treatment to integrate fruquintinib as a standard of care together with the new therapeutic combinations that recently showed clinical benefit for chemorefractory mCRC, in both molecularly selected (e.g. KRASG12C or HER2 amplification) and in non-oncogenic driven patients.

P3, N=420, Not yet recruiting, Biotech Pharmaceutical Co., Ltd.

Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation...In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance.

P1, N=12, Active, not recruiting, University of California, Irvine | Trial completion date: Jan 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Aug 2023

P2, N=28, Completed, Heinrich-Heine University, Duesseldorf | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Jan 2024 | Trial primary completion date: Oct 2024 --> Jan 2024

P2, N=13, Completed, Providence Health & Services | Active, not recruiting --> Completed

P2, N=230, Active, not recruiting, Agenus Inc. | Trial primary completion date: Jan 2024 --> Feb 2025

This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.

P3, N=120, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

The presence of a KRASG12 mutation had no detrimental effect on OS among patients treated in SUNLIGHT. The benefit of FTD/TPI plus bevacizumab over FTD/TPI alone was confirmed independently of KRASG12 status.

P2, N=176, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Nov 2024

P1; Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=28, Active, not recruiting, Heinrich-Heine University, Duesseldorf | Trial completion date: Apr 2024 --> Nov 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment.

P2, N=340, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

P3, N=700, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

The experts agreed with most of the proposed items on 3L treatment of mCRC, prioritizing therapeutic options that increase survival and preserve QoL, while facilitating the possibility that patients can continue to be treated later.

P1, N=715, Recruiting, Taiho Pharmaceutical Co., Ltd. | N=367 --> 715 | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

P2, N=45, Recruiting, Zhejiang University | Trial primary completion date: Dec 2023 --> Dec 2024

P3, N=432, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2024 --> Nov 2025

P1, N=18, Recruiting, OHSU Knight Cancer Institute | Phase classification: P1b --> P1

P2, N=50, Recruiting, Qilu Hospital of Shandong University

P2, N=73, Not yet recruiting, UNICANCER

P1/2, N=160, Recruiting, Centre Georges Francois Leclerc | Not yet recruiting --> Recruiting | Trial completion date: Mar 2026 --> Oct 2026 | Trial primary completion date: Mar 2024 --> Oct 2026

Clinical strategy changes, including gastrectomy, HER2 testing, and approval of new drugs, may be associated with improved OS in patients with AGC. In the last 4 years, a remarkable improvement has been observed in patients with LM.

Based on the findings of molecular and pathological examinations(RAS: wild type; BRAF: wild type; MSI: negative; HER2: negative), the following chemotherapy regimens were administered: first-line, FOLFIRI plus panitumumab(PANI); second-line, mFOLFOX6; third-line, trifluridine/tipiracil; fourth- line, regorafenib...Therefore, rechallenge therapy with anti-epidermal growth factor receptor(EGFR)drugs, cetuximab(CET)and irinotecan(IRI), was administered 13 months after the final course of FOLFIRI plus PANI treatment. After 4 courses of CET plus IRI, the size of the 2 metastatic tumors markedly decreased and his tumor marker levels normalized.