Clinical trial NCT05508737: Pembrolizumab and Trifluridine/Tipiracil With Previously Treated Advanced Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric and Gastroesophageal Junction Adenocarcinoma
Keywords: Pembrolizumab(Keytruda®)
Trifluridine/Tipiracil (Lonsurf®)
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2022-08-19
Enrollment: 75
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase Ib (DLT)
timeFrame: within first 6weeks
measure: Phase Ib (RP2D)
timeFrame: within first 6weeks
measure: Objective response rate (ORR)
timeFrame: 6months after the last treatment of the last subject
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 6months after the last treatment of the last subject
measure: Progression-free survival (PFS) as assessed per RECIST 1.1
timeFrame: 6months after the last treatment of the last subject
measure: Disease control rate (DCR) as assessed per RECIST 1.1
timeFrame: 6months after the last treatment of the last subject
measure: Duration of response (DOR) as assessed per RECIST 1.1
timeFrame: 6months after the last treatment of the last subject
measure: Number of participants with Adverse Events that are related to treatment
timeFrame: Throughout the overall trial period as well as up to 3months after the last dose study treatment for each subject
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Yonsei Cancer Center, Yonsei University College of Medicine
name: SUN YOUNG Rha
role: PRINCIPAL_INVESTIGATOR
References: