Lenvatinib and Pembrolizumab Simultaneous Combination Study

Phase 2

Completed

• Conditions: Advanced Gastric Cancer
• Interventions: Drug: Lenvatinib; Drug: Pembrolizumab

• Registration Number: NCT03609359
• Lead Sponsor: National Cancer Center Hospital East

Brief Summary

The efficacy and safety of the use of pembrolizumab in combination with lenvatinib.

Detailed Description

In this study, if combination therapy with lenvatinib and pembrolizumab in patients with gastric cancer is judged to be effective, a prospective treatment regimen can be expected for a larger number of participating subjects.

The anticipated disadvantages include any adverse events associated with lenvatinib and pembrolizumab. To minimize the risk and disadvantages of adverse events, the data center together with the Data and Safety Monitoring Committee will monitor any adverse events in the present trial to determine whether or not they are within the expected range. These bodies will also conduct a thorough examination in the event that serious or unexpected adverse events occur, and adopt an appropriate system to take any necessary actions.

Study Timeline

• Study First Submitted: 2018-07-23
• Study First Submitted QC: 2018-07-24
• Study First Posted: 2018-08-01
• Study Start: 2018-10-03
• Primary Completion: 2021-04-30
• Study Completion: 2021-04-30
• Results First Submitted: 2023-04-12
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-27
• Last Update Submitted: 2025-03-27
• Results First Posted: 2025-04-16
• Last Update Posted: 2025-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Patients have histologically or cytologically confirmed advanced or recurrent gastric cancer.

2. Patients at least 20 years of age on the day of providing consent.

3. Patients have measurable disease as defined by RECIST 1.1 as determined by investigator.

4. Patients with a performance status of 0 or 1 on the Eastern Cooperative Oncology Group.

5. Patients with adequate organ function at the time of enrollment as defined below:

   • Neutrophil count ≥1200mm3
   • Platelet count ≥7.5 × 104/mm3
   • Hemoglobin (Hb) ≥ 8.0 g/dL,
   • Total bilirubin ≤1.5 mg/dL
   • Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 100 IU/L for subjects with liver metastases ≤ 200 IU/L
   • Creatinine ≤1.5-times the upper limit of normal
   • International normalized ratio (INR) ≤ 1.5
   • Urinary protein : It satisfies one of the following (if any of the inspection criteria are satisfied, other examination may not be carried out) (i) Urinary protein (test paper method) is 2+ or less (ii) Urine Protein Creatinine (UPC) ratio <3.5 (iii) 24-hour urine protein was measured, urinary protein ≦ 3500 mg

6. Patients who not received a blood transfusion within 7 days of registration.

7. Patients have recovered adverse events associated with chemotherapy, radiation and surgical operation as pretreatment to Grade 1 or lower with CTCAE v4.0 excluding stable symptoms (eg alopecia, peripheral sensory neuropathy, skin hyperpigmentation, dysgeusia etc.).

8. Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment.

9. Patients capable of taking oral medication

10. Patients who provided written informed consent to be subjects in this trial

Exclusion Criteria

1. Patients who received prior anticancer treatment within 14 days (or 5 times the half-life time, whichever is shorter) or any investigational agent within 28 days prior to the first dose of study drugs.
2. Patients who have undergone surgical treatment and radiotherapy with in 2 weeks before enrollment.
3. Patients with a history of prior treatment with Lenvatinib or any anti-programmed death 1, anti-programmed ligand death 1, or anti-programmed ligand death 2.
4. Patients with hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents.
5. Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment.
6. Patients with symptomatic brain metastasis.
7. Patients with a history of New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
8. Patients have an active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months
9. Patients have severe (hospitalization required) complications (intestinal palsy, intestinal obstruction, pulmonary fibrosis, diabetes difficult to control, heart failure, myocardial infarction, unstable angina, renal failure, liver failure, mental disease, cerebrovascular disease etc).
10. Patients with a history of a gastrointestinal perforation and /or gastrointestinal fistula within 6 months before enrollment.
11. Patients with active hepatitis.
12. Patients with a history of human immunodeficiency virus (HIV).
13. Patients with active symptoms or signs of interstitial lung disease.
14. Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease
15. Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy) or immunosuppressants, or who have received such a therapy <14 days before enrollment.
16. Patients have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis
17. Patients who are administered live vaccines <30 days before the initiation of treatment with the investigational drug.
18. Patients have serious non-healing wound, ulcer, or bone fracture.
19. Females who are pregnant or breastfeeding
20. Patients have no intention to comply with the protocol or cannot comply.
21. Patients were judged unsuitable as subject of this trial by investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lenvatinib + Pembrolizumab	Lenvatinib	Lenvatinib and Pembrolizumab will be administrated simultaneously for advanced gastric cancer patients.
Lenvatinib + Pembrolizumab	Pembrolizumab	Lenvatinib and Pembrolizumab will be administrated simultaneously for advanced gastric cancer patients.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	12 months	ORR will be defined as the proportion of patients who achieved Complete Response (CR) or Partial Response (PR) for best overall response (confirmation required) according to immune-related RECIST (irRECIST) and RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	12 months	* 1 "Progression" will be PD based on diagnostic imaging according to overall response by RECIST v1.1. The day of the imaging test will be defined as the day of progression. When the treatment are discontinued due to clinical PD and diagnostic imaging can't be performed, the day of clinical PD will be defined as the day of progression.; * 2 Surviving patients, who are not assessed as progression will be censored on the last day when no progression is confirmed on imaging (last day of PFS confirmed); * 3 For patients who died without being assessed as progression, whether to consider to be an "event on the day of death" or "censoring on the last day of PFS confirmed" should be decided at the time of data review performed prior to data fixation. In principle, they should be "an "event on the day of death" unless the period from the last day of PFS confirmed to the day of death is long.
Overall Survival (OS)	28 months	* The period will be from the day of enrollment, as the starting date of the computation, to the day of death of any cause. Surviving patients should be censored on the last day of PFS confirmed. Patients who are lost to follow up should be censored on the last day when their survival is confirmed before being lost to follow up.; * The protocol for this clinical trial stipulated that the observation period was "2 years from the date of registration of the last case." Meanwhile, OS was stipulated as "the period from the date of registration to the date of death from any cause. For surviving cases, the period was censored at the date of last confirmed survival." The observation period varied by case, with follow-up surveys lasting up to 28 months.
Disease Control Rate (DCR)	2 years	The DCR will be defined as the percentage of patients who achieved CR or PR, or Stable Disease (SD) for best overall response according to RECIST v1.1.
Number of Participants With Adverse Events (AEs)	Basically 2 years, maximum 28 months	* Number of each AE of the worst grade occurring in this study was evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and tabulated throughout all cycles. This study also includes a special note regarding abnormal laboratory values. When clinical signs and symptoms observed in this study were elicited, diagnosis and related data were collected based on whether they were due to abnormal laboratory values. Therefore, for example, grading results for liver dysfunction may differ between non-hematologic toxicities and laboratory values.; * Adverse-Events occurrences means "prevalence proportion" of any undesirable occurrence based on investigator's medical decision in this study.
Objective Response Rate (irORR)	12 months	Objective response rate (irORR) according to immune-related (ir) RECIST

Trial Locations

Locations (1)

NationalCCHE; 🇯🇵 Kashiwa, Tokyo, Japan