Pembrolizumab and Trifluridine/Tipiracil With Previously Treated Advanced Gastric Cancer

July 9, 2025 updated by: Sun Young Rha, Yonsei University

Open-label Phase II Study With Lead-in Safety Cohort of Pembrolizumab (Keytruda®) and Trifluridine/Tipiracil (Lonsurf®) Combination Treatment in Patients With Previously Treated Advanced Gastric Cancer

This is a two-part, Phase II, open-label, single arm, multi-center study to determine the efficacy of pembrolizumab in combination with TAS-102 (trifluridine/tipiracil) in patients with advanced gastric cancer who have progressed after prior treatment with or without anti-PD-1/PD-L1 agent, and to further assess the safety and tolerability of this combination treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a two-part, Phase II, open-label, single arm, multi-center study to determine the efficacy of pembrolizumab in combination with TAS-102 (trifluridine/tipiracil) in patients with advanced gastric cancer who have progressed after prior treatment with or without anti-PD-1/PD-L1 agent, and to further assess the safety and tolerability of this combination treatment. In lead-in-safety cohort, recommended dose of trifluridine/tipiracil combined with pembrolizumab will be determined with dose-limiting toxicity (DLT) and safety. Pembrolizumab dose will be fixed with current recommended dose of 400mg IV every 6 weeks (Q6W). There will be 2 dose cohort for trifluridine/tipiracil; dose level 1 is trifluridine/tipiracil 35mg/m2 BID, D1-5, D8-12, every 4 weeks (Q4W) and dose level 0 is trifluridine/tipiracil 30mg/m2 BID, D1-5, D8-12, every 4 weeks (Q4W). DLT will be evaluated during first 6 weeks. In the subsequent expansion Phase II part, patients will be recruited from four sites to evaluate the efficacy and safety of the combination therapy in 2 cohorts, anti-PD-1/PD-L1 inhibitor naive and exposure cohorts.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital
      • Seoul, Korea, Republic of
        • Severance Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Has provided written informed consent fo the trial.
  2. Is male or female at least 18 years of age.
  3. Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma.
  4. Has previously received at least 2 prior regiments.
  5. Has a life expectancy of at least 3 months.
  6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Have 1 or more measurable disease as determined by RECIST 1.1.
  8. Is able to take medications orally.
  9. Has adequate organ function as defined by the following criteria.
  10. Is willing to follow and follow research procedures.
  11. A male participant must agree to use a contraception of this protocol during the treatment period and for at least 120 days post TAS-102.
  12. A female participant is eligible to participate if she is not pregnant or breastfeeding.

Exclusion Criteria:

  1. Has other concurrently active malignancies.
  2. Has received prior therapy with TAS-102.
  3. Is contraindicated for pembrolizumab and/or TAS-102, or have severe hypersensitivity to any of those drugs and/or their excipients.
  4. Has any unresolved ≥Grade 2 toxicity (per CTCAE v5.0) attributed to any prior therapies at the time of enrollment.
  5. Has had major surgery within 2 weeks prior to first dose of study interventions.
  6. Has known active central nervous system (CNS) metastases.
  7. Has received radiotherapy for gastric cancer treatment within 2 weeks prior to the first dose of study drugs.
  8. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.
  9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  10. Has participated has used an investigational device within 4 weeks prior to the first dose of study intervention.
  11. Has a history of uncontrollable or significant cardiovascular disease.
  12. Has active (significant or uncontrolled) gastrointestinal bleeding.
  13. Has active autoimmune disease that has required systemic treatment in the past 2 years.
  14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  15. Has an active, unresolved infection requiring systemic therapy.
  16. Has a known history of Human Immunodeficiency Virus (HIV) infection.
  17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection.
  18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  19. Has had an allogenic tissue/solid organ transplant.
  20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: IO experienced
Pembrolizumab 400 mg every 6 weeks (Q6W), trifluridine/tipiracil at 35 or 30 mg/m2 twice daily (BID) for 5 days a week (D1-5, D8-12) with 2 days rest for 2 weeks, followed by a 14-day rest, repeated every 4 weeks (Q4W)
Drug: Pembrolizumab (Keytruda®), Trifluridine/Tipiracil (Lonsurf®)
arms : Pembrolizumab 400 mg every 6 weeks (Q6W), trifluridine/tipiracil at 35 or 30 mg/m2 twice daily (BID) for 5 days a week (D1-5, D8-12) with 2 days rest for 2 weeks, followed by a 14-day rest, repeated every 4 weeks (Q4W)
Other Names:
  • Pembrolizumab (Keytruda®)
  • Trifluridine/Tipiracil (Lonsurf®)
Experimental: IO non-experienced
Pembrolizumab 400 mg every 6 weeks (Q6W), trifluridine/tipiracil at 35 or 30 mg/m2 twice daily (BID) for 5 days a week (D1-5, D8-12) with 2 days rest for 2 weeks, followed by a 14-day rest, repeated every 4 weeks (Q4W)
Drug: Pembrolizumab (Keytruda®), Trifluridine/Tipiracil (Lonsurf®)
arms : Pembrolizumab 400 mg every 6 weeks (Q6W), trifluridine/tipiracil at 35 or 30 mg/m2 twice daily (BID) for 5 days a week (D1-5, D8-12) with 2 days rest for 2 weeks, followed by a 14-day rest, repeated every 4 weeks (Q4W)
Other Names:
  • Pembrolizumab (Keytruda®)
  • Trifluridine/Tipiracil (Lonsurf®)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 6months after the last treatment of the last subject
The proportion of patients in complete remission (CR) or partial remission (PR) among the best response (BOR) assessed by the investigator according to RECIST 1.1.
6months after the last treatment of the last subject
Phase Ib (DLT)
Time Frame: within first 6weeks
Phase Ib (Lead-in safety cohort): Dose-limiting toxicity (DLT)
within first 6weeks
Phase Ib (RP2D)
Time Frame: within first 6weeks
Phase Ib (Lead-in safety cohort): Recommended Phase 2 dose (RP2D)
within first 6weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 6months after the last treatment of the last subject
Defined as the time start of study treatment until death by cause. Any subject not known to have died at the time of the analysis will be censored on the last recorded date on which the subject was known to be alive.
6months after the last treatment of the last subject
Progression-free survival (PFS) as assessed per RECIST 1.1
Time Frame: 6months after the last treatment of the last subject
Defined as the time from start of study treatment until the date of objective disease progression or death. Progression is defined in accordance with RECIST v1.1 criteria.
6months after the last treatment of the last subject
Disease control rate (DCR) as assessed per RECIST 1.1
Time Frame: 6months after the last treatment of the last subject
Defined as the proportion of subjects with a best objective response (BOR) of complete response (CR) or Partial response (PR), or stable disease maintained for a minium of twelve weeks from start of treatment, as defined by the RECIST 1.1.
6months after the last treatment of the last subject
Duration of response (DOR) as assessed per RECIST 1.1
Time Frame: 6months after the last treatment of the last subject
Defined as the time from the investigator's first determination of objective response to the first of disease progression or death according to RECIST 1.1.
6months after the last treatment of the last subject
Number of participants with Adverse Events that are related to treatment
Time Frame: Throughout the overall trial period as well as up to 3months after the last dose study treatment for each subject
Safety and tolerability of the pembrolizumab and TAS-120 combination therapy as determined by adverse events categorized in accordance with CTCAE 5.0 Criteria.
Throughout the overall trial period as well as up to 3months after the last dose study treatment for each subject

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: SUN YOUNG Rha, Yonsei Cancer Center, Yonsei University College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 2, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 19, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4-2022-0582

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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