Study of Lenvatinib Plus Pembrolizumab in IO Refractory mRCC Patients With Brain Metastases

NCT07011849 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2024-0331NCI-2025-04029
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-center, open-label phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with renal cell carcinoma (RCC) and brain metastasis who were previously treated with immune checkpoint blockade.

Conditions

Renal Cell Carcinoma; Brain Metastasis

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Second Course: Retreatment with Pembrolizumab

EXPERIMENTAL

Drug: Pembrolizumab

Treatment with Pembrolizumab and Lenvatinib

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

Given by IV

Second Course: Retreatment with Pembrolizumab; Treatment with Pembrolizumab and Lenvatinib

Lenvatinib DRUG

Given by mouth

Treatment with 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:

• Male/female participants .18 years of age on the day of signing informed consent withhistologically confirmed diagnosis of RCC, irrespective of histologic will be enrolled in this study. Because no dosing or adverse event data are currently available on the use of lenvatinib in combination with pembrolizumab in patients \<18 years of age, children are excluded from this study.
• Criteria for brain metastasis:
• Has at least 1 measurable brain metastasis with no prior history of SRT: Presence of at least 1 independently verified, non-irradiated, measurable brain metastasis, defined as at least 5 mm AND twice the MRI slice thickness, but less than or equal to 3 cm, that can be accurately assessed at baseline and suitable for accurate repeated measurements.
• Has at least 1 measurable brain metastasis with prior history of SRT to other brain metastases: A history of SRT for brain metastases is allowed up to 1 week before study treatment provided that neurologic sequelae are resolved. If the patient will be enrolled to the study immediately after SRS it is encouraged to have 1-5 measurable untreated measurable lesion(s) remain, defined as at least 5 mm AND twice the MRI slice thickness, but less than or equal to 3 cm.
• Has no measurable brain metastasis with prior SRT: A history of immediate prior SRT for brain metastases is allowed up to 1 week before study treatment provided that neurologic sequelae are resolved.
• If the patient had prior SRT, progression in irradiated lesion 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 \>10 mg prednisone or equivalent per day 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).
• Patients with brain metastasis that have not received prior systemic therapy may be eligible to enroll in this study.
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 10 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.
• Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 10), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 10 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 10 during the treatment period and for at least 120 days after the last dose of study treatment.
• Participants must have progressed on any prior line of treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression.

You may not qualify if:

• Has symptomatic brain metastasis requiring immediate procedure (surgery, radiation treatment), or corticosteroids in dosing exceeding 10 mg daily of prednisone equivalent.
• Has received whole brain radiation treatment previously
• Has overt hemorrhagic brain metastasis
• Has received prior therapy with lenvatinib
• Has clinical or radiographic evidence of leptomeningeal disease
• Has had major surgery within 3 weeks prior to first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. Patients must have adequately recovered from major surgery and has no ongoing surgical complications.
• Has prior history of .Grade 3 toxicity attributed to immune checkpoint inhibitor treatment.
• Has severe hypersensitivity (.Grade 3) to pembrolizumab and/or any of its excipients.
• 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.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Has a history of (non-infectious, non-radiation-induced) pneumonitis not responsive to steroids or has current pneumonitis/interstitial lung disease. Patients will also be excluded if there are respiratory issues including active infection or require supplemental oxygen for activities of daily living.
• Has preexisting .Grade 3 gastrointestinal or non-gastrointestinal fistula.
• Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
• Has urine protein .1 g/24 hours. Note: Participants with proteinuria .2+ (.100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
• Has a left ventricular ejection fraction (LVEF) below or equal to the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Renal Cell; Brain Neoplasms

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Eric Jonasch, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 10, 2025
• Study Start: June 4, 2025
• Primary Completion: August 7, 2025
• Study Completion: August 7, 2025
• Last Updated: August 13, 2025

Record last verified: 2025-08