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Pembrolizumab and Lenvatinib for the Treatment of Advanced, Unresectable, or Metastatic Gastroesophageal Adenocarcinoma | Clinical Trials | Clareo Health

RECRUITINGEARLY_PHASE1

Pembrolizumab and Lenvatinib for the Treatment of Advanced, Unresectable, or Metastatic Gastroesophageal Adenocarcinoma

A Pilot Study of Pembrolizumab and Lenvatinib Combination Therapy in Patients With Previously Treated Advanced Gastroesophageal Adenocarcinoma

NCT05041153•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This early phase I trial studies the effect of pembrolizumab and lenvatinib in treating patients with gastroesophageal adenocarcinoma that has spread to other places in the body (advanced/metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and lenvatinib may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVE: I. To estimate the overall response rate (ORR) of pembrolizumab plus lenvatinib by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in adult subjects with previously treated advanced (unresectable and/or metastatic) gastroesophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To evaluate the duration of response (DOR), disease control rate (DCR), time-to-progression (TTP), progression-free survival (PFS), using RECIST 1.1 and immune-related (i)RECIST criteria and overall survival (OS). II. To determine the safety and tolerability of pembrolizumab plus lenvatinib in adult subjects with previously treated advanced (unresectable and/or metastatic) gastroesophageal adenocarcinoma. EXPPLORATORY OBJECTIVES: I. To perform exploratory biomarker analyses to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with clinical outcomes (DOR, DCR, TTP, PFS, and OS) using RESIST 1.1 and iRECIST. II. To explore the association between PD-L1 expression by immunohistochemistry (IHC), shed PD-L1 levels, somatic gene expression profiling (18-gene T-cell inflamed GEP) and antitumor efficacy of pembrolizumab based on RECIST 1.1 imaging criteria as well as OS. III. To explore the relationship between genomic variation and response to the treatment administered. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and lenvatinib orally (PO) once daily (QD). Treatment repeats every 42 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•The subject (or legally acceptable representative if applicable) provides written informed consent for the trial
•Male and female subjects who are at least 18 years of age on day of signing informed consent with histologically and cytologically documented diagnosis as gastric or gastroesophageal adenocarcinoma
•Has a documented, previously treated, advanced (unresectable and/or metastatic) gastroesophageal adenocarcinoma that is incurable and for which prior first-line or later-line standard of care (SOC) treatments have failed. Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence
•Has submitted an evaluable tissue sample for biomarker analysis from a newly obtained irradiated. The tumor tissue submitted for analysis must be from a single tumor tissue specimen and of sufficient quantity and quality to allow biomarker study (see laboratory manual). A "newly obtained" tumor specimen, defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1, for biomarker characterization will be required for enrollment of all subjects. Tissue from tumor progressing at a site of prior radiation (at least 6 weeks interval after last radiation) may be allowed for biomarker characterization upon agreement from Merck. Subjects for whom newly-obtained samples cannot be provided (e.g., inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Merck
•Has measurable disease based on RECIST 1.1 as assessed by the Investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
•Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale within 5 days of starting study treatment
•Has a life expectancy of greater than 3 months per the judgment of the investigators
•Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =\< 150/90 mm Hg at screening and no change in antihypertensive medications within 1 week of cycle 1 day 1
•Absolute neutrophil count (ANC) \>= 1,500/uL (specimens must be collected within 5 days prior to the start of study treatment)
•Platelets \>= 100,000/uL (specimens must be collected within 5 days prior to the start of study treatment)
+18 more criteria

Exclusion Criteria

•Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment.
•* Note: Subjects who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
•Has had major surgery within 3 weeks prior to first dose of study interventions.
•* Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
•Has preexisting \>= grade 3 gastrointestinal or non-gastrointestinal fistula
•Has urine protein \>= 1 g/24 hours.
•* Note: subjects with proteinuria \>= 2+ (\>= 100 mg/dL) on urine dipstick testing/urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria
•Has significant gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
•Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
+25 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

February 14, 2022

Primary Completion Date

December 30, 2026

Completion Date

December 30, 2026

Last Updated

January 12, 2026

Enrollment

ESTIMATED participants

Conditions

Advanced Gastric AdenocarcinomaAdvanced Gastroesophageal Junction AdenocarcinomaClinical Stage III Gastric Cancer AJCC v8Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IV Gastric Cancer AJCC v8Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IVA Gastric Cancer AJCC v8Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IVB Gastric Cancer AJCC v8Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Metastatic Gastric AdenocarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaPathologic Stage III Gastric Cancer AJCC v8Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IIIA Gastric Cancer AJCC v8Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IIIB Gastric Cancer AJCC v8Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IIIC Gastric Cancer AJCC v8Pathologic Stage IV Gastric Cancer AJCC v8Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage III Gastric Cancer AJCC v8Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Unresectable Gastric AdenocarcinomaUnresectable Gastroesophageal Junction Adenocarcinoma

Interventions

Lenvatinib

DRUG

Pembrolizumab

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 12, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Pembrolizumab and Lenvatinib for the Treatment of Advanced, Unresectable, or Metastatic Gastroesophageal Adenocarcinoma

Inclusion Criteria

Exclusion Criteria

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

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Multi-omics Based Prediction of Treatment Response to Immunotherapy Combined with Chemotherapy in Advanced Gastric/Gastroesophageal Junction Cancer.