Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and Other Tumor Types and Brain Metastases

Who is this study for? Patients with Brain Metastases, Tumor
What treatments are being studied? Pembrolizumab+Lenvatinib
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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. Cohort 3 will be comprised of solid tumor types with established (e.g., renal cell carcinoma \[RCC\], endometrial cancer) or preliminary clinical evidence (e.g., gastric cancer, colorectal cancer) of efficacy of programmed cell death-1 (PD-1) and angiogenesis inhibitors. The study will be conducted using a Simon's optimal two-stage design, and approximately 87 patients will be enrolled concurrently (n=29 per cohort). The primary endpoint is intracranial objective response rate (ORR) as assessed by the modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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 (Cohort 3) with brain metastasis and with or without active extracranial disease will be enrolled in this study.

• 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 accurate repeated measurements and with a tumor diameter of 0.5-3 cm on magnetic resonance imaging \[MRI\]).

‣ 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) remain. If the patient had prior whole brain radiation therapy or SRS, progression in any measurable brain metastasis must have occurred at least 1 month after the end of radiation therapy for the irradiated lesion to be counted as measurable.

⁃ Patients can have asymptomatic (no neurologic signs or symptoms, not requiring immediate local intervention \[surgery or radiosurgery\] or systemic glucocorticoid therapy \[within 10 days prior to study treatment initiation\]) OR minimally symptomatic brain metastases (requiring ≤10 mg prednisone or equivalent per day and not requiring immediate surgical or radiation therapy in the opinion of the treating investigator and a radiation therapy or neurosurgical consultant).

• 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 during this period.

• 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 subjects

‣ 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

• 2 Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.

• • Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.

Locations
United States
Texas
M D Anderson Cancer Center
RECRUITING
Houston
Contact Information
Primary
Jordi Rodon Ahnert, MD, PhD
jrodon@mdanderson.org
(713) 792-5603
Time Frame
Start Date: 2022-01-20
Estimated Completion Date: 2025-04-30
Participants
Target number of participants: 104
Treatments
Other: Cohort 1
Patients with TNBC and brain metastases
Other: Cohort 2
Patients with NSCLC and brain metastases
Other: Cohort 3
Patients with other solid tumor types and brain metastases
Authors
Jordi Ahnert
Sponsors
Leads: M.D. Anderson Cancer Center
Collaborators: Eisai Inc.

This content was sourced from clinicaltrials.gov