Lonsurf (trifluridine/tipiracil) / Servier, Otsuka, TTY Biopharm - LARVOL DELTA

A Study to Access Intravenous (IV) Telisotuzumab Adizutecan in Combination With IV Bevacizumab Compared to Standard of Care IV Bevacizumabin Combination With Oral Trifluridine and Tipiracil in Adult Participants With Refractory Metastatic Colorectal Cancer (clinicaltrials.gov) - P3 | N=990 | Recruiting | Sponsor: AbbVie | N=700 ➔ 990

Enrollment change • Colorectal Cancer • Oncology • Solid Tumor

CA102N Combined With TAS-102 Compared to Bevacizumab Combined With TAS-102 in Subjects With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=100 | Suspended | Sponsor: Holy Stone Healthcare Co., Ltd | Trial completion date: Oct 2025 ➔ Sep 2031 | Not yet recruiting ➔ Suspended | Trial primary completion date: Feb 2025 ➔ Oct 2030

Trial completion date • Trial primary completion date • Trial suspension • Colorectal Cancer • Oncology • Solid Tumor

Clinical outcomes and prognostic factors with trifluridine/tipiracil plus bevacizumab in RAS wild-type metastatic colorectal cancer: real-world evidence from the BeTAS study (ESMO 2026) - No abstract available

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

Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer. (PubMed, J Clin Oncol) - "In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC."

Journal • P3 data • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study. (PubMed, J Clin Oncol) - P3 | "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."

Journal • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) treated with sotorasib and panitumumab (pmab) versus trifluridine/tipiracil (T/T) or regorafenib (rego) in CodeBreaK 300. (ASCO-GI 2024) - P3 | "In CodeBreaK 300, both doses of sotorasib resulted in better HRQoL and a trend to decreased risk of deterioration vs the control group. In addition to improved clinical outcomes, these findings provide further evidence on the benefit of soto+pmab in patients with chemorefractory mCRC. Clinical trial information: NCT05198934."

Clinical • HEOR • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Precemtabart tocentecan (M9140), an anti-CEACAM5 ADC with exatecan payload, in patients with metastatic colorectal cancer (mCRC): Results from the dose optimization of the phase 1 PROCEADE CRC-01 study. (ASCO 2025) - P1, P1/2 | " This global Phase 1 study in 3L adult patients with locally advanced/mCRC (ECOG PS ≤1; previous irinotecan therapy) evaluates clinical activity, safety, and tolerability of precemtabart tocentecan... These preliminary results corroborate the encouraging efficacy and safety data from the dose escalation part of the PROCEADE CRC-01 study, with no new relevant safety findings. ORR was higher at 2.8 mg/kg, with similar tolerability at both doses. The ORR of 24.1% (13.8% confirmed) at 2.8 mg/kg compares favorably with current monotherapy SoCs (ORRs 1-2%) and recent phase 3 data with trifluridine–tipiracil + bevacizumab (ORR 6.1%) in 3L+ mCRC."

Clinical • Metastases • P1 data • Anemia • Colorectal Cancer • Febrile Neutropenia • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CEACAM5

Sotorasib plus panitumumab versus standard-of-care for chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreak 300 phase III study (ESMO 2023) - P3 | "Methods In the CodeBreaK 300 (NCT05198934) global, open label study, 160 pts with chemorefractory KRAS G12C-mutated mCRC were randomized 1:1:1 to soto 960 mg daily plus pani 6 mg/kg IV (soto960+pani; n=53), soto 240 mg daily plus pani 6 mg/kg IV (soto240+pani, n=53), or investigator's choice of TAS-102 or regorafenib (n=54). Table: LBA10 Efficacy by BICR Soto960+Pani n=53 Soto240+Pani n=53 SOC n=54 Median PFS, months (95% CI) 5.6 (4.21, 6.31) 3.9 (3.71, 5.75) 2.2 (1.94, 3.91) ORR, % (95% CI) 26.4 (15.3, 40.3) 5.7 (1.2, 15.7) 0 (0.0, 6.6) Number of responders 14 3 0 Median DOR, months (range) 4.4 (1.9+, 6.0+) NR (1.8+, 3.8+) -- DCR, % (95% CI) 71.7 (57.7, 83.2) 67.9 (53.7, 80.1) 46.3 (32.6, 60.4) CI, confidence interval; DCR, disease control rate; DOR, duration of response; NR, not reached; ORR, objective response rate Conclusions In the first phase 3 study for a KRASG12C-inhibitor plus an anti-EGFR antibody in chemorefractory mCRC, the primary endpoint was met..."

Late-breaking abstract • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

A phase II trial of TAS-102 in patients with colorectal cancer with ctDNA-defined minimal residual disease post-adjuvant therapy: Results from the MD Anderson INTERCEPT Program. (ASCO-GI 2024) - P2 | "We demonstrate the feasibility of identifying and enrolling MRD+ pts through screening during surveillance onto therapeutic trials and show the ability of an experimental therapy to convert patients to MRD negative status, a necessary but not sufficient step for disease eradication. Preliminary results suggest that treatment with TAS-102 is effective in inducing ctDNA clearance in the short term in most pts, but with no evidence of persistent clearance. Updated results including 6-m ctDNA levels and survival data will be presented."

Circulating tumor DNA • Clinical • Minimal residual disease • P2 data • Residual disease • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase I study of trifluridine/tipiracil in combination with gemcitabine (gem) and nab-paclitaxel (nab-P) in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2023) - P1 | "The RP2D is Gem 800mg/m2, Nab-P 100mg/m2, and L 25mg/m2. This combination was well tolerated with expected toxicities of myelosuppression with prolonged responses seen. Clinical trial information: NCT04046887."

Clinical • Combination therapy • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A phase II study of intrapatient dose escalation of biweekly trifluridine/tipiracil plus bevacizumab for colorectal cancer (E-BiTS study). (PubMed, ESMO Open) - "Intrapatient dose escalation of biweekly FTD/TPI plus BEV was feasible and well tolerated and may enhance the efficacy of refractory mCRC treatment. Nonetheless, further studies are warranted to validate this individualized dosing strategy."

Journal • P2 data • Colorectal Cancer • Febrile Neutropenia • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • RAS

PolyPEPI1018 vaccine in combination with TAS-102 in participants with late-stage microsatellite-stable metastatic colorectal cancer (MSS mCRC): A phase Ib study to evaluate safety, tolerability, immunogenicity and efficacy (OBERTO-201). (ASCO 2023) - P1 | "To our knowledge, this is the first study investigating combination of a cancer vaccine with TAS-102 chemotherapy in advanced MSS mCRC. Our results show that PolyPEPI1018 plus TAS-102 was well-tolerated with few grade 3 AEs beyond what is expected with TAS-102 monotherapy. Despite no objective tumor responses could be detected, correlative data suggest contribution of PolyPEPI1018-induced immunological responses to the improved clinical benefit and the combination warrants further testing."

Clinical • Combination therapy • Metastases • P1 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Musculoskeletal Pain • Oncology • Pain • Solid Tumor • KRAS

Post-hoc central radiological review of the ALTAIR study in patients with molecular residual disease (MRD) following curative resection of colorectal cancer (CRC). (ASCO-GI 2026) - P3 | "Although exploratory in nature, this post-hoc analysis with central radiological review resulted in a statistically significant DFS benefit with FTD/TPI in patients with MRD-positive CRC post-definitive treatment. This stresses the importance of pre-specified blinded independent central radiological review in clinical trials for which documentation of recurrence/progression is critical to the primary analysis."

Clinical • Residual disease • Retrospective data • Review • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

RELATIVITY-123: A phase 3, randomized, open-label study of nivolumab (NIVO) + relatlimab (RELA) fixed-dose combination (FDC) versus regorafenib or trifluridine + tipiracil (TAS-102) in later-line metastatic colorectal cancer (mCRC). (ASCO-GI 2023) - P3 | "The study initiated in April 2022 and is enrolling globally. Clinical trial information: NCT05328908."

Clinical • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • LAG3 • MSI • PD-L1 • RELA

ACCRU-GI-1810: Trifluridine/tipiracil (FTD-TPI) or paclitaxel (PAC) in combination with ramucirumab (RAM) for patients (pts) with previously treated advanced gastroesophageal adenocarcinoma (GEA)—An investigator-initiated, randomized non-inferiority phase 2 study. (ASCO-GI 2026) - P2 | "Although NI was not achieved due to early closure and small sample size, FTD-TPI+RAM was relatively safe and associated with less neuropathy compared with PAC+RAM. This regimen warrants further evaluation for pts in whom neuropathy limits taxane use."

Clinical • Combination therapy • Head-to-Head • Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Propensity Score–Matched (PSM) Analysis of Trifluridine-Tipiracil Plus Bevacizumab (FTD/TPI+Bev) vs Chemotherapy retreatment in Pretreated Metastatic Colorectal Cancer (mCRC). (ESMO 2026) - No abstract available

Metastases • Colorectal Cancer • Oncology • Solid Tumor

Phase II study of TAS-OX (TAS-102 and oxaliplatin) plus bevacizumab for late-line colorectal cancer. (ASCO-GI 2023) - P2 | " Eligibility included measurable CRC previously treated with all approved drugs per TAS package insert (irinotecan, oxaliplatin, 5FU, anti-VEGF, anti-EGF) as appropriate, PS = 0-1, labs within usual range, neuropathy < grade 2, ability to take oral meds, appropriate contraception...For the first 40 pts, 385 cycles were given (mean = 7 cycles, median 8) with 18 pts (45%) requiring dose reductions (1 dose reduction = 9 pts, 2 = 6, 3 = 3), and 9 receiving (peg)/filgrastim... In patients with late-line CRC and candidates for TAS (trifluridine/tipiracil), treatment with TAS plus OX is both well tolerated and active. RR is higher than single agent and 78% (95% CI, 60-91%) of patients had stable disease or response, with 60% receiving 8 or more cycles. Randomized trials comparing to single agent TAS are warranted in this setting."

P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A phase II trial of TAS-102 in patients with colorectal cancer with ctDNA-defined minimal residual disease post-adjuvant therapy compared to synthetic control cohort: Results from the MD Anderson INTERCEPT program. (ASCO 2024) - P2 | "It is possible to identify MRD+ pts through screening during surveillance and enroll them onto therapeutic trials. Preliminary results suggest that treatment with TAS-102 is effective in inducing ctDNA clearance in the short term, and in doing so, may prolong DFS for pts receiving additional therapy compared to the SC. However, without evidence of persistent clearance this is unlikely to result in an increased cure fraction."

Circulating tumor DNA • Clinical • Minimal residual disease • P2 data • Residual disease • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MSI

Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Advanced, Refractory Biliary Tract Carcinoma. (PubMed, Oncologist) - P2 | "The combination of trifluridine/tipiracil plus irinotecan is a potential treatment option for patients with advanced, refractory BTCs with good functional status and no targetable mutations. A larger randomized trial is needed to confirm these results. (ClinicalTrials.gov Identifier: NCT04072445)."

Journal • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Hematological Disorders • Oncology • Solid Tumor

Single-arm, single-center, exploratory study of Vibecotamab combined with TAS-102 in the treatment of relapsed/metastatic RAS wild-type colorectal cancer patients who have failed second-line standard therapy (ChiCTR) - P=N/A | N=31 | Not yet recruiting | Sponsor: Shanghai East Hospital; Shanghai East Hospital

IO biomarker • New trial • Colorectal Cancer • Oncology • Solid Tumor • CTCs • PD-L1

Phase I dose-escalation study of trifluridine/tipiracil plus XB2001 and bevacizumab in chemorefractory advanced colorectal cancer: The TASKIN study (ESMO-GI 2024) - P1/2 | "This supports testing the combination of TAS-102 plus XB2001 (an IL-1α monoclonal antibody). In the phase 1/2 TASKIN study (NCT05201352), patients (pts) with chemorefractory metastatic CC after failure of oxaliplatin, irinotecan, and fluoropyrimidine were enrolled and received XB2001 from 250 mg to 1000 mg every 2 weeks plus FTD-TPI 35 mg/m2. FTD-TPI plus XB2001 and bevacizumab demonstrated acceptable safety with promising efficacy in chemorefractory metastatic CC. The study continues as a randomized phase 2 study comparing FTD-TPI and bevacizumab with or without XB2001."

IO biomarker • Metastases • P1 data • Anemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CD8 • CTAG1B • IL6 • PD-L1

Monitoring botensilimab- and balstilimab-induced T-cell dynamics in refractory mismatch repair proficient metastatic colorectal cancer. (ASCO 2025) - P2 | "In this trial patients were randomized into BOT (75mg or 150mg Q6W, 4x) monotherapy or in combination with BAL (240mg Q2W, for 2 years), versus standard of care (regorafenib or trifluridine/tipiracil). Deep T cell repertoire profiling detected dynamics of circulating T cells with quantitative and qualitative difference related to ICI response. Immune cell tracking from liquid biopsies is a powerful tool to quantify ICI efficacy in real time."

IO biomarker • Metastases • Mismatch repair • pMMR • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

STELLAR-303: A phase 3 study of XL092 in combination with atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer (mCRC). (ASCO-GI 2023) - P3 | "Regorafenib or trifluridine-tipiracil are approved for patients in the third- or later-line setting, but survival benefit is limited. While immune checkpoint inhibitor (ICI) therapy is approved (nivolumab ± ipilimumab, and pembrolizumab) in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, the MSI-H phenotype is limited to ~5% of mCRC patients. In phase 1/2 trials, ICIs in combination with VEGFR2 multi-kinase inhibitors (MKIs) have demonstrated encouraging clinical activity in mCRC, including atezolizumab and durvalumab (ICIs) in combination with the MKI cabozantinib, with data suggesting a greater benefit in RAS wild-type (wt) vs mutant (mut) disease (Abrams TA, et al...Enrollment is ongoing. Clinical trial information: NCT05425940."

Clinical • Combination therapy • IO biomarker • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • AXL • MSI • PD-1 • PD-L1

Phase 1b study to assess the safety of neoadjuvant trifluridine/tipiracil with concurrent radiation in resectable stage II/III rectal cancer. (ASCO-GI 2023) - P1b | "Importantly, TFD/TPI has superior radio-sensitization in vitro compared to 5-fluorouracil, and we hypothesize that this can improve the tumor response of patients...The study was activated December 2019 and has accrued 8 of intended 18 patients. Clinical trial information: NCT04104139."

Clinical • P1 data • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

Trifluridine/tipiracil plus capecitabine and bevacizumab as upfront treatment for metastatic colorectal cancer: Results of the phase I TriComB study (ESMO-GI 2024) - P1/2 | "Here, we present safety and preliminary activity results of the phase 1 TriComB study, an open-label, multicenter, phase 1/2 trial, evaluating FTD/TPI in combination with cap and bev in mCRC pts. Patients with previously untreated mCRC, ineligible for oxaliplatin- and/or irinotecan- based regimens, were enrolled. The sequential combination of cap and FTD/TPI with bev is feasible. The phase 2 of the study is ongoing to evaluate antitumor activity of this regimen in the same patients' population."

Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor