Pembrolizumab and Trifluridine/Tipiracil With Previously Treated Advanced Gastric Cancer

NCT05508737 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 4-2022-0582
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Gastric and Gastroesophageal Junction Adenocarcinoma

Keywords

Pembrolizumab(Keytruda®); Trifluridine/Tipiracil (Lonsurf®)

Outcome Measures

Primary Outcomes (3)

• Phase Ib (DLT)

  Phase Ib (Lead-in safety cohort): Dose-limiting toxicity (DLT)

  within first 6weeks

• Phase Ib (RP2D)

  Phase Ib (Lead-in safety cohort): Recommended Phase 2 dose (RP2D)

  within first 6weeks

• Objective response rate (ORR)

  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

Secondary Outcomes (5)

• Overall survival (OS)

  6months after the last treatment of the last subject

• Progression-free survival (PFS) as assessed per RECIST 1.1

  6months after the last treatment of the last subject

• Disease control rate (DCR) as assessed per RECIST 1.1

  6months after the last treatment of the last subject

• Duration of response (DOR) as assessed per RECIST 1.1

  6months after the last treatment of the last subject

• Number of participants with Adverse Events that are related to treatment

  Throughout the overall trial period as well as up to 3months after the last dose study treatment for each subject

Study Arms (2)

IO experienced

EXPERIMENTAL

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®)

IO non-experienced

EXPERIMENTAL

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®)

Interventions

Pembrolizumab (Keytruda®), Trifluridine/Tipiracil (Lonsurf®) DRUG

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)

Also known as: Pembrolizumab (Keytruda®), Trifluridine/Tipiracil (Lonsurf®)

IO experienced; IO non-experienced

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written informed consent fo the trial.
• Is male or female at least 18 years of age.
• Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma.
• Has previously received at least 2 prior regiments.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have 1 or more measurable disease as determined by RECIST 1.1.
• Is able to take medications orally.
• Has adequate organ function as defined by the following criteria.
• Is willing to follow and follow research procedures.
• 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.
• A female participant is eligible to participate if she is not pregnant or breastfeeding.

You may not qualify if:

• Has other concurrently active malignancies.
• Has received prior therapy with TAS-102.
• Is contraindicated for pembrolizumab and/or TAS-102, or have severe hypersensitivity to any of those drugs and/or their excipients.
• Has any unresolved ≥Grade 2 toxicity (per CTCAE v5.0) attributed to any prior therapies at the time of enrollment.
• Has had major surgery within 2 weeks prior to first dose of study interventions.
• Has known active central nervous system (CNS) metastases.
• Has received radiotherapy for gastric cancer treatment within 2 weeks prior to the first dose of study drugs.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.
• 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.
• Has participated has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has a history of uncontrollable or significant cardiovascular disease.
• Has active (significant or uncontrolled) gastrointestinal bleeding.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active, unresolved infection requiring systemic therapy.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (2)

Severance Hospital

Seoul, 03722, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Interventions

pembrolizumab; Trifluridine; tipiracil; trifluridine tipiracil drug combination

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• SUN YOUNG Rha

  Yonsei Cancer Center, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Severance Hospital, Yonsei University Health System

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: August 19, 2022
• Study Start: December 1, 2022
• Primary Completion: November 2, 2025
• Study Completion: December 1, 2025
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)