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

NCT05041153 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-1265NCI-2021-09188
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Metastatic Gastric Adenocarcinoma; Pathologic Stage IIIC Gastric Cancer AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Advanced Gastroesophageal Junction Adenocarcinoma; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Metastatic Gastroesophageal Junction Adenocarcinoma; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage III Gastric Cancer AJCC v8; Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8; Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Unresectable Gastric Adenocarcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma; Advanced Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  through study completion, an average of 1 year

Study Arms (1)

Treatment (pembrolizumab, lenvatinib)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 and lenvatinib PO QD, Treatment repeats every 42 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Lenvatinib; Biological: Pembrolizumab

Interventions

Lenvatinib DRUG

Given by PO

Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Treatment (pembrolizumab, lenvatinib)

Pembrolizumab BIOLOGICAL

Given by IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, lenvatinib)

Eligibility Criteria

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

You may qualify if:

• 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)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) (specimens must be collected within 5 days prior to the start of study treatment)
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (specimens must be collected within 5 days prior to the start of study treatment)
• Creatinine clearance should be calculated per institutional standard
• Total bilirubin \< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN (specimens must be collected within 5 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases (specimens must be collected within 5 days prior to the start of study treatment)

You may not qualify if:

• 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.
• Note: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
• Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
• Significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability
• Prolongation of corrected QT (QTc) interval to \> 480 ms
• Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Interventions

lenvatinib; pembrolizumab

Study Officials

• Mariela Blum

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 10, 2021
• Study Start: February 14, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)