Pembrolizumab And Lenvatinib In Leptomeningeal Metastases

NCT04729348 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 20-533
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research is to examine if an experimental drug combination impacts the survival rate of individuals with Leptomeningeal Metastases This research study involves an experimental drug combination. The names of the study drugs involved in this study are:

• Pembrolizumab
• Lenvatinib

Conditions

Solid Tumor; Solid Tumor, Adult; Leptomeningeal Metastasis

Keywords

Solid Tumor; Solid Tumor, Adult; Leptomeningeal Metastasis

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants alive at 6 months

  The proportion of patients alive at 6 months will be summarized with a 90% confidence interval estimated using the method of Atkinson and Brown (Biometrics, 1985), which allows for the two-stage design. Based on a sample of 19 patients, the confidence interval will be no wider than 33%

  6 months

Secondary Outcomes (10)

• Proportion of Participants with Grade 3 or higher toxicities

  first dose of study treatment up to the 30-Day Post Drug Visit up to 30 Months

• Proportion of evaluable participants with intracranial/intraspinal response

  30 Months

• Proportion of evaluable participants with extracranial response

  30 Months

• Intracranial/intraspinal Progression Free Survival (IPFS)

  30 Months

• Median Intracranial/intraspinal Progression Free Survival (IPFS)

  30 Months

Study Arms (1)

PEMBROLIZUMAB and LENVATINIB

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment, including evaluations and follow up visits. * PEMBROLIZUMAB daily, every 3 weeks * LENVATINIB daily every 3 weeks

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

Oral, daily, dosage per protocol

Also known as: Keytruda®

PEMBROLIZUMAB and LENVATINIB

Lenvatinib DRUG

Oral, daily, dosage per protocol

Also known as: Lenvima™

PEMBROLIZUMAB and LENVATINIB

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed solid malignancy.
• Leptomeningeal metastases, as determined by: 1) positive CSF cytology, or 2) MRI suggestive of leptomeningeal metastases and atypical cytology.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with lenvatinib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status ≤ 1 (Karnofsky ≥70%, see Appendix A)
• Participants must have normal organ and marrow function; all screening labs should be performed within 14 days of treatment initiation.
• Eligibility Criteria for Organ and Marrow Function
• Hematological
• Absolute neutrophil count (ANC) ≥1500/μL
• Platelets ≥100 000/μL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Renal
• \--- Creatinine ≤1.5 × ULN OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Hepatic
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)

You may not qualify if:

• Participants who have received prior systemic anti-cancer therapy including investigational agents within 14 days of protocol treatment. Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Participant must have recovered adequately from the toxicity and/or complications from any prior surgical procedures prior to starting therapy. Lenvatinib should be held for 4 weeks following a major surgical procedure, 2 weeks following a minor surgical procedure.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. No testing for HIV, Hepatitis B, and Hepatitis C is required unless mandated by local health authority.
• Participants who are receiving any other investigational agents.
• Has a diagnosis of immunodeficiency.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known additional malignancy that is progressing or requires active treatment (except for patients receiving letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy). 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.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of system.
• Requires treatment with high dose systemic corticosteroids defined as dexamethasone \>2mg/day or bioequivalent within 7 days of initiating therapy.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• Nancy Wang, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 28, 2021
• Study Start: March 8, 2021
• Primary Completion: January 17, 2024
• Study Completion: January 17, 2024
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)