Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and … (NCT05064280) | Clinical Trial Compass
RecruitingPhase 2
Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and Other Tumor Types and Brain Metastases
United States104 participantsStarted 2022-01-20
Plain-language 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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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 \[MRI\]).
✓. 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.
What they're measuring
1
To establish the intracranial ORR of the pembrolizumab and lenvatinib combination in patients with TNBC or NSCLC and brain metastases, as assessed according to the modified RECIST
Timeframe: through study completion, an average of 1 year
✓. The patient (or legally acceptable representative if applicable) provides written informed consent for the study.
Exclusion criteria
✕. 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 this trial.
✕. 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 are superficially located (cortical-based brain metastasis) and leptomeningeal spread is suspected, a work-up for leptomeningeal disease (LMD) should be performed (MRI and lumbar puncture with CSF cytology). If LMD is not confirmed, the treating physician, neuro-oncologist, or brain metastasis multidisciplinary team should make a clinical call and exclude the patient if LMD dissemination is likely.
✕. 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 agent or chemotherapy is allowed.
✕. Has received prior systemic anticancer therapy including investigational agents within 28 days prior to study treatment initiation.
✕. 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 equivalent, and not have had radiation pneumonitis. Any radiation to the brain or spinal cord/cauda equina must have been completed within \>3 weeks from study treatment initiation.
✕. 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.