CLINICAL TRIALS PROFILE FOR TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

505(b)(2) Clinical Trials for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT07235293 ↗	A Study to Test DSP107 in Combination With Atezolizumab in Comparison With Fruquintinib as a New Treatment for Colorectal Cancer.	NOT_YET_RECRUITING	Novotech (Australia) Pty Limited	PHASE2	2025-11-15	This clinical study is testing whether a new combination of medicines (DSP107 and atezolizumab) is more effective and safer than an existing treatment (fruquintinib) for people with advanced colorectal cancer that is microsatellite stable (MSS). Participants will be randomly assigned to receive one of the two treatments, and researchers will monitor how well the cancer responds, how safe the treatments are, and how the body processes them. The study hopes to show that the new combination can improve outcomes for patients with this type of colorectal cancer.
New Combination	NCT07235293 ↗	A Study to Test DSP107 in Combination With Atezolizumab in Comparison With Fruquintinib as a New Treatment for Colorectal Cancer.	NOT_YET_RECRUITING	Kahr Bio Australia Pty Ltd	PHASE2	2025-11-15	This clinical study is testing whether a new combination of medicines (DSP107 and atezolizumab) is more effective and safer than an existing treatment (fruquintinib) for people with advanced colorectal cancer that is microsatellite stable (MSS). Participants will be randomly assigned to receive one of the two treatments, and researchers will monitor how well the cancer responds, how safe the treatments are, and how the body processes them. The study hopes to show that the new combination can improve outcomes for patients with this type of colorectal cancer.

All Clinical Trials for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01955837 ↗	Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia	Completed	Taiho Pharmaceutical Co., Ltd.	Phase 3	2013-09-01	To compare the effects of TAS-102 with placebo in patients with metastatic colorectal cancer refractory or intolerable to standard chemotherapies.
NCT02654639 ↗	Ph 2 Study of TAS-102 / Bevacizumab Maintenance Therapy Post Induction Chemotherapy in Metastatic Colorectal Cancer	Terminated	Georgetown University	Phase 2	2016-02-01	Phase II study of TAS-102 plus bevacizumab switch maintenance therapy in patients with mCRC
NCT03278106 ↗	TAS-102 in Treating Advanced Biliary Tract Cancers	Active, not recruiting	National Cancer Institute (NCI)	Phase 2	2017-10-20	This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
NCT03278106 ↗	TAS-102 in Treating Advanced Biliary Tract Cancers	Active, not recruiting	Mayo Clinic	Phase 2	2017-10-20	This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
NCT03297710 ↗	TAS-102 and Radiation Therapy in Treating Patients With Rectal Cancer That Is Locally Recurrent, Metastatic, or Cannot Be Removed by Surgery	Active, not recruiting	National Cancer Institute (NCI)	Phase 1	2017-12-11	This phase I trial studies the side effects and best dose of trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) when given together with radiation therapy in treating patients with rectal cancer that has come back, spread to other places in the body, or cannot be removed by surgery. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving TAS-102 with radiation therapy may kill more tumor cells.
NCT03297710 ↗	TAS-102 and Radiation Therapy in Treating Patients With Rectal Cancer That Is Locally Recurrent, Metastatic, or Cannot Be Removed by Surgery	Active, not recruiting	Mayo Clinic	Phase 1	2017-12-11	This phase I trial studies the side effects and best dose of trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) when given together with radiation therapy in treating patients with rectal cancer that has come back, spread to other places in the body, or cannot be removed by surgery. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving TAS-102 with radiation therapy may kill more tumor cells.
NCT03306394 ↗	A Study of Trifluridine/Tipiracil (Also Known as S 95005 or TAS-102) in Patients With a Pretreated Colorectal Cancer That Has Spread (Metastatic).	Completed	ADIR, a Servier Group company	Phase 3	2016-10-18	The purpose of this study is to collect additional safety and efficacy data during treatment with trifluridine / tipiracil in patients with a pretreated metastatic colorectal cancer (mCRC). Eligible patients may receive an early access to trifluridine / tipiracil through this clinical study until progression of disease, unacceptable toxicity, investigator decision, patient refusal or until market authorization or reimbursement has been granted by the relevant Authority of the country where that patient is treated or until trifluridine / tipiracil is available by a doctor's prescription or can be accessed from another source or Sponsor decision.

Clinical Trial Conditions for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Condition Name

Condition Name for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Intervention	Trials
Metastatic Colorectal Cancer	22
Colorectal Cancer	9
Stage IV Colorectal Cancer AJCC v8	7
Stage IVB Colorectal Cancer AJCC v8	6

Condition MeSH

Condition MeSH for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Intervention	Trials
Colorectal Neoplasms	61
Adenocarcinoma	17
Colonic Neoplasms	9
Carcinoma	8

Clinical Trial Locations for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Trials by Country

Trials by Country for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Location	Trials
United States	151
China	48
Italy	28
Japan	23
Australia	16

Trials by US State

Trials by US State for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Location	Trials
California	14
Texas	13
Florida	11
Illinois	8
Minnesota	8

Clinical Trial Progress for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Clinical Trial Phase

Clinical Trial Phase for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Clinical Trial Phase	Trials
PHASE3	5
PHASE2	24
PHASE1	7

Clinical Trial Status

Clinical Trial Status for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Clinical Trial Phase	Trials
Recruiting	49
Not yet recruiting	14
NOT_YET_RECRUITING	12

Clinical Trial Sponsors for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Sponsor Name

Sponsor Name for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Sponsor	Trials
National Cancer Institute (NCI)	15
Servier	6
Academic and Community Cancer Research United	4

Sponsor Type

Sponsor Type for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Sponsor	Trials
Other	98
Industry	42
NIH	15

Tipiracil Hydrochloride and Trifluridine (TAS-102): Clinical Trials Update, Market Analysis, and Projections

Last updated: April 23, 2026

What is tipiracil hydrochloride and trifluridine and what product matters commercially?

Tipiracil hydrochloride and trifluridine is the fixed-dose oral combination component of TAS-102 (trifluridine, a nucleoside analog; tipiracil hydrochloride, a thymidine phosphorylase inhibitor that increases trifluridine exposure). Commercial positioning in major markets is tied to TAS-102 and its line extensions across colorectal cancer and, in selected programs, other solid tumors.

Core composition (drug substance concept)

• Trifluridine: nucleoside analog
• Tipiracil hydrochloride: enzymatic protection (reduces trifluridine degradation)

Key marketed indication (anchor for market sizing)

• Metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine, oxaliplatin, and irinotecan (standard-of-care history for TAS-102 adoption).
  This is the foundational label that drives baseline revenue and subsequent attempts to expand into earlier lines and combination regimens. (FDA label for TAS-102). [1]

What do the latest clinical-trials signals show (pipeline direction and uptake risk)?

This update is constrained to trial programs and approvals for which label-supporting facts are available in the cited sources. The TAS-102 development focus remains:
1) line advancement in colorectal cancer
2) combinations (immune therapy, targeted agents, anti-VEGF/EGFR pathway)
3) evaluation in tumor types with nucleoside analog sensitivity hypotheses

Trial activity pattern (what matters for projection)

Commercial impact tends to follow two paths:

• Label expansion (new lines, new geographies, new combinations with defined response endpoints)
• Safety-and-tolerability durability in real-world adoption and longer treatment exposure

For TAS-102, market uptake is also affected by:

• hematologic AE profile (neutropenia and anemia are recurrent operational considerations)
• dosing modifications (dose interruption and reduction frequency is a meaningful cost-of-care driver)

Which clinical-trial and regulatory facts anchor the market view?

Approved use as a baseline demand driver

The U.S. label for TAS-102 establishes the main revenue perimeter through defined prior-therapy requirements. The FDA indication in the label is:

• metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan; either refractory or progressed. (FDA label). [1]

Mechanistic rationale linked to clinical positioning

Tipiracil hydrochloride increases systemic exposure of trifluridine by inhibiting thymidine phosphorylase-mediated metabolism, supporting oral dosing in heavily pretreated settings. (Mechanism summary in FDA materials and review documents linked to labeling). [1]

What is the current market landscape (demand, competition, and substitution)?

Demand drivers

• High unmet need in mCRC after standard agents: TAS-102 benefits from being an oral option with an established survival benefit profile in the refractory setting.
• Treatment sequencing: in many care pathways TAS-102 competes for time after progression on first-line and subsequent regimens.
• Oral convenience and logistics: oral regimens can reduce infusion capacity constraints; however, they shift monitoring burden to outpatient hematologic safety.

Competitive set (substitution pressure)

TAS-102 faces substitution from other late-line options in mCRC:

• oral fluoropyrimidine strategies and other nucleoside analog approaches
• targeted therapies conditioned on biomarkers (where applicable)
• immunotherapy combinations in MSI-H/dMMR subsets (when criteria are met)

The practical commercial reality is that TAS-102’s strongest pocket is MSS-propensity refractory settings, where guideline options are limited.

Where does the commercial opportunity expand (and where does it stall)?

Expansion vectors

• Earlier-line uptake: if phase II/III combo evidence supports label movement toward 2nd or 1st/2nd lines, addressable population increases and treatment duration rises.
• Combination regimens: combinations can extend beyond the monotherapy label perimeter if efficacy thresholds are met and safety remains manageable.

Stall vectors (projection risks)

• Safety management: neutropenia-driven dose modifications can blunt dose intensity and reduce net effective exposure, which affects outcomes and physician confidence in earlier lines.
• Competing efficacy in line-specific compartments: in earlier lines, performance needs to match or exceed what is available from regimen standards.

Clinical trial update (TAS-102): what to monitor next

For market projection accuracy, the key clinical and regulatory milestones to track are: 1) phase III readouts that target earlier-line mCRC positioning for label expansion 2) regulatory submissions that add combination indications 3) post-approval evidence confirming tolerability and real-world persistence

This update is anchored by the existing label perimeter and assumes that future value comes from either:

• label expansion in colorectal cancer, or
• credible label movement into additional solid tumor categories.

Market analysis: sizing logic and projection framework

Revenue logic (how TAS-102 demand translates)

Revenue for TAS-102 is driven by:

• eligible mCRC patients meeting prior-therapy criteria
• choice persistence (time on therapy and treatment course)
• pricing and rebate dynamics by market
• safety-driven dose intensity reductions

Projection outcomes (three-scenario view)

Given TAS-102’s already-established label perimeter, projections are primarily sensitive to:

• magnitude of line advancement
• combination differentiation and payer uptake
• sustainability of clinical differentiation under head-to-head substitution pressures

A practical projection framework uses three scenarios:

Base case (label perimeter holds; incremental expansion)

• mCRC demand remains stable in the refractory compartment
• modest lift from geographic expansion and incremental regimen adoption

Upside case (successful earlier-line and combination label expansions)

• increased treatable population
• higher average annual patient-days from longer sequences

Downside case (slower adoption or stronger substitution in late-line compartments)

• tighter payer controls tied to hematologic safety management
• shift to alternative late-line oral regimens or biomarker-conditioned approaches

Key business indicators that determine whether projections skew upside or downside

1) Label scope and reimbursement access

The largest revenue swing comes from label expansions that translate into insurer-covered indications and low-friction prior authorization.

2) Dose management economics

Neutropenia and anemia management affects:

• clinic visits, labs, and supportive care (G-CSF usage patterns)
• patient adherence to oral schedules

3) Treatment duration and persistence

For oral oncology, adherence and dose interruptions materially affect net revenue per treated patient.

Projections: what the pathway implies for 3-to-5 year market growth

Near-term (0 to 24 months)

• Growth depends on adoption breadth within existing label populations and incremental geographic or payer coverage improvements.
• Major upside requires positive late-stage data that can move into filings.

Mid-term (24 to 60 months)

• Mid-term growth is most sensitive to label expansions in earlier lines or newly accepted combination regimens.
• If earlier-line penetration does not occur, growth stays limited to substitution dynamics within refractory mCRC.

Clinical evidence and labeling anchor: regulatory fact set used for this projection

• TAS-102 indication in the U.S. for metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan is the primary demand perimeter for this market model. (FDA label). [1]
• The drug combination is mechanistically designed to maintain trifluridine exposure through thymidine phosphorylase inhibition. (FDA labeling and review materials). [1]

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Key Takeaways

• Tipiracil hydrochloride and trifluridine (TAS-102) is commercially defined by its U.S. label for metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan. [1]
• Market growth is primarily a function of line advancement and combination label expansion, with meaningful downside risk from substitution in later lines and hematologic safety-driven dose modifications.
• Projections hinge on whether late-stage evidence expands TAS-102 beyond the current refractory compartment into earlier treatment sequences with durable tolerability.

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FAQs

1) What is the main indication that drives current TAS-102 demand?

Metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan. [1]

2) What is the mechanism that makes the combination work?

Tipiracil hydrochloride inhibits thymidine phosphorylase, which helps sustain trifluridine exposure for oral dosing. [1]

3) What is the biggest clinical adoption bottleneck for projection?

Hematologic toxicity management, which affects dose intensity and persistence. (Reflected in clinical use considerations tied to labeled use.) [1]

4) Where is the most likely upside for revenue?

Regulatory expansion into earlier lines and accepted combination regimens in mCRC, which increases the eligible patient pool beyond the refractory compartment. [1]

5) What would most likely cap the upside?

Failure of combination or earlier-line programs to achieve label-expanding benefit while maintaining tolerability relative to competing regimens in specific line settings. [1]

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References

[1] U.S. Food and Drug Administration. TAS-102 (trifluridine and tipiracil hydrochloride) prescribing information / label. FDA. https://www.accessdata.fda.gov/