A Phase II a Study of Lenvatinib, a Multi-targeted Tyrosine Kinase Inhibitor, Combined With Pembrolizumab (PD-1 Inhibitor) for the Treatment of Metastatic Gastroesophageal Cancer Patients Who Have Progressed on First or Subsequent Line Therapies

NCT03321630 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-00626
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, single arm phase II study, to determine the overall response rate for the combination of lenvatinib and pemrolizumab in patients with metastatic gastroesophageal cancer who have progressed on first or subsequent line therapies. Given the significant cross talk between angiogenesis and the immune response, combined therapy with lenvatinib and pemrolizumab in advanced gastroesophageal cancer patient will provide improved outcomes compared to standard treatment with currently approved agents.

Conditions

GastroEsophageal Cancer; Gastric Cancer

Keywords

Pebrolizumab; Lenvatinib

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate

  Overall response rate as measured by RECIST 1.1; percentage of participants who experience a best overall response of either Complete Response (CR) or Partial Response (PR).

  Up to Month 18

• Overall Survival (OS)

  Estimated using Kaplan-Meier curve; interval from start of treatment to death due to any cause.

  Up to Month 18

• Progression-Free Survival (PFS)

  Estimated using Kaplan-Meier Curves; interval between the date of start of treatment and the earlier date of objective disease progression per RECIST 1.1 criteria or death due to any cause in the absence of progression.

  Up to Month 18

Study Arms (1)

Lenvatinib & Pembrolizumab

OTHER

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

Lenvatinib 20 mg orally each day on days 1-7

Lenvatinib & Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 200mg intravenously, to be initiated on day 8, and continued every 3 weeks, in combination with daily lenvatinib 20 mg

Lenvatinib & Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be greater than 18 years of age on day of signing informed consent.
• Have histologically or cytologically confirmed metastatic or recurrent gastric or GEJ adenocarcinoma.
• Have measurable disease based on RECIST 1.1.
• Must have received and have progressed, or are intolerant to at least one systemic regimen (platinum- or fluoropyrimidine-based chemotherapy regimen for metastatic or recurrent disease.)
• If Her2 positive, must have received and have progressed or are intolerant to treatment with trastuzumab for metastatic or recurrent disease.
• Subjects must consent to provide archival tumor tissue (initial and subsequent tumor biopsy samples, if possible) for correlative biomarker studies.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Adequately controlled blood pressure with or without antihypertensive medications defined as BP \< 140/90 mmHg at screening and no change in antihypertensive mediation within 1 week prior to the Screening Visit.
• Demonstrate adequate organ function as defined in Table 5, all screening labs should be performed within 10 days of treatment initiation.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.5.2) must be willing to use an adequate method of contraception as outlined in Section 5.5.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Male subjects of childbearing potential (Section 5.5.2) must agree to use an adequate method of contraception as outlined in Section 5.5.2 - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or lenvatinib or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, a minimum of four weeks must have passed and they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Subjects having \>1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein \>1g/24h will be ineligible.
• Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
• Prolongation of QTcF interval to \>480ms
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug.
• Bleeding disorders or active significant bleeding (i.e. hemoptysis, hematochezia, hematemesis) within 3 weeks.
• Thrombotic disorders or use of anticoagulants, such as warfarin, requiring therapeutic international normalized ratio (INR) monitoring. (treatment with low molecular weight heparin (LMWH) or direct acting oral anti-coagulants is allowed.)

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (2)

NYU Langone Health

New York, New York, 10016, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: Paul Oberstein
• Organization: NYU Langone Health

paul.oberstein@nyulangone.org

2127316120

Study Officials

• Paul E. Oberstein, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: October 25, 2017
• Study Start: October 24, 2017
• Primary Completion: March 10, 2023
• Study Completion: January 16, 2024
• Last Updated: March 27, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)