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New treatment option for Brain Metastases
Official title Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and Other Tumor Types and Brain Metastases
ClinicalTrials.gov ID: NCT05064280
What this study is testing
What is Pembrolizumab?
Pembrolizumab is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for brain metastases.
Also referred to as KEYTRUDA®.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is a single-center, open-label, multi-cohort Phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with solid tumors and brain metastases. The study will be comprised of 3 patient cohorts: triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and solid tumor types other than TNBC and NSCLC.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Patients are eligible to be included in the study only if all the following criteria apply:
- Male/female patients who are at least 18 years of age on the day of signing informed consent with histologically or cytologically confirmed TNBC...
- Has at least 1 measurable brain metastasis: Presence of at least 1 independently verified measurable brain metastasis in accordance with mRECIST...
- Previous SRS and excision of up to 5 brain metastases are permitted at least 3 weeks prior to study treatment initiation, provided that neurologic...
- Patients can have asymptomatic (no neurologic signs or symptoms, not requiring immediate local intervention [surgery or radiosurgery] or systemic...
You likely can't join if
- Patients are excluded from the study if any of the following criteria apply, unless medically indicated and after approval by study chair/IRB office:
- Has NSCLC with an oncogenic driver mutation (mutation(s) in EGFR, ERBB2, or BRAF V600E; fusion/rearrangement(s) in ALK, ROS1, NTRK, or RET; or MET...
- Has hepatocellular carcinoma. NOTE: patients with hepatocellular carcinoma and brain metastasis are excluded from this trial because the dose of...
- Has symptomatic or untreated spinal cord compression. Patients with clinical or radiographic evidence of leptomeningeal metastases or other...
- Has received prior therapy with lenvatinib or other antiangiogenic tyrosine kinase inhibitor alone or in combination with a PD-1/PD-L1 inhibitor...
- Has received prior systemic anticancer therapy including investigational agents within 28 days prior to study treatment initiation.
See the full eligibility criteria
Who can join
- Patients are eligible to be included in the study only if all the following criteria apply:
- Male/female patients who are at least 18 years of age on the day of signing informed consent with histologically or cytologically confirmed TNBC (Cohort 1), NSCLC (Cohort 2), or solid tumors other than TNBC and NSCLC...
- Has at least 1 measurable brain metastasis: Presence of at least 1 independently verified measurable brain metastasis in accordance with mRECIST (Appendix 1) that can be accurately assessed at baseline and suitable for...
- Previous SRS and excision of up to 5 brain metastases are permitted at least 3 weeks prior to study treatment initiation, provided that neurologic sequelae have completely resolved and measurable untreated lesion(s)...
- Patients can have asymptomatic (no neurologic signs or symptoms, not requiring immediate local intervention [surgery or radiosurgery] or systemic glucocorticoid therapy [within 10 days prior to study treatment...
- Extracranial disease is not required and if present, it can be measurable or non-measurable (RECIST v1.1).
- A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 6 OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 6 during the treatment period and for at least 120 days after the last dose of study treatment.
- A male patient must agree to use contraception as detailed in Appendix 6 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm...
- The patient (or legally acceptable representative if applicable) provides written informed consent for the study.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 7).
- Has a life expectancy ≥12 weeks.
- Has adequate organ function within 28 days of study treatment initiation as defined below:
- Absolute neutrophil count ≥1000/µL (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
- Platelet count ≥100 000/µL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
- Hemoglobin ≥9.0 g/dL
- Total bilirubin ≤1.5 × upper limit of normal (ULN); if hepatic metastases are present, ≤2.0 × ULN
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN; if hepatic metastases are present, ≤5.0 × ULN
- Creatinine clearance ≥50 mL/min
- International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
- Adequately controlled blood pressure with 0 or 1 antihypertensive medication (defined as blood pressure ≤150/90 mmHg at screening and no changes in antihypertensive medication within 7 days of Day 1 of Cycle 1).
- Hepatitis B and C screening tests are not required unless:
- Known history of HBV or HCV infection
- As mandated by local health authority 11.1 Hepatitis B positive people
- Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
- Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention 11.2 Participants with history of HCV infection...
- Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
What rules you out
- Patients are excluded from the study if any of the following criteria apply, unless medically indicated and after approval by study chair/IRB office:
- Has NSCLC with an oncogenic driver mutation (mutation(s) in EGFR, ERBB2, or BRAF V600E; fusion/rearrangement(s) in ALK, ROS1, NTRK, or RET; or MET amplification). KRAS or PIK3CA mutation are allowed.
- Has hepatocellular carcinoma. NOTE: patients with hepatocellular carcinoma and brain metastasis are excluded from this trial because the dose of lenvatinib approved for this disease is different than the ones used in...
- Has symptomatic or untreated spinal cord compression. Patients with clinical or radiographic evidence of leptomeningeal metastases or other metastatic systemic disease are not allowed. In cases where brain metastases...
- Has received prior therapy with lenvatinib or other antiangiogenic tyrosine kinase inhibitor alone or in combination with a PD-1/PD-L1 inhibitor. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD L2, or anti-CTLA-4...
- Has received prior systemic anticancer therapy including investigational agents within 28 days prior to study treatment initiation.
- Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. Patients with immunotherapy-related AEs of a permanent nature but...
- Patients must have recovered adequately from any complications from major surgery. Withhold lenvatinib treatment for at least 1 week prior to elective surgery. Do not administer lenvatinib for at least 2 weeks following...
- Has received radiotherapy within 14 days prior to study treatment initiation. Patients must have recovered from all radiation-related toxicities, not require corticosteroids in dosing exceeding 10 mg daily of prednisone...
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to study treatment initiation. Administration of killed vaccines is allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days or 5 half-lives, whichever is shorter, prior to study treatment initiation...
- Contraindications to MRI (implanted metal device or foreign bodies) or MRI contrast (insufficient renal function or allergy).
- A WOCBP who has a positive screening serum pregnancy test within 7 days prior to Day 1 of Cycle 1 (see Appendix 6).
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study...
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in...
- Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or lenvatinib and/or any of their excipients.
- Has a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study treatment initiation. Inhaled or topical...
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus.
- Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are...
- Known history of HBV and HCV infection
- As mandated by local health authority
- Active tuberculosis (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is...
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
- GI tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g...
- Unable to swallow and retain oral medications.
- Has significant cardiac impairment including but not limited to history of congestive heart failure greater than New York Heart Association Class II (Appendix 8), unstable angina, myocardial infarction or stroke within...
- Has prolongation of QTc using Fridericia's formula (QTcF) to \>480 ms.
- Has gastric or esophageal varices that may require treatment.
- Having a GI bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) with 28 days of enrollment.
- Has bleeding or thrombotic disorder(s) or uses anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring. Treatment with low molecular weight heparin is allowed.
- Electrolyte abnormalities that have not been corrected.
- Patients having \>1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<1 g/24 hours.
- Has had an allogeneic tissue/solid organ transplant.
- Has radiographic evidence of intratumoral cavitation, encasement, or invasion of a major blood vessel.
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.