Pembrolizumab Plus Lenvatinib in REcurrent ccRCC Patients Failing permbroLizUmab aDjuvant trEatment

NCT07460206 | Not Yet Recruiting Phase 2

• 1 other identifier: GOIRC-01-2024
• Study Type: interventional
• Target: 108
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being performed as a single-arm open-label study in order to provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with advanced ccRCC who have progressed on Pembrolizumab as their prior therapy in the adjuvant RCC setting.

Conditions

ccRCC

Keywords

clear cell renal cell carcinoma; Pembrolizumab; lenvatinib

Outcome Measures

Primary Outcomes (2)

• Primary outcome

  PFS: the time from first dose to the first documented PD or death from any cause, whichever occurs first

  Five years

• Primary outcome

  Objective response (OR): a confirmed complete response (CR) or partial response (PR)

  Five years

Secondary Outcomes (4)

• Secondary outcome

  Five years

• Secondary Outcome

  Five years

• Secondary outcome

  Five years

• Secondary outcome

  Five years

Study Arms (1)

Arm A

EXPERIMENTAL

Pembrolizumab The planned dose of pembrolizumab for this study is 200 mg IV every 3 weeks (Q3W). Pembrolizumab will be given for a maximum of 2 years i.e. a total of 35 cycles. Participants who complete study intervention after 2 years of pembrolizumab are eligible for up to 1 year of additional pembrolizumab (second course) upon experiencing disease progression. Lenvatinib The planned dose of Lenvatinib for this study is 20 mg once daily (QD). Lenvatinib will be taken orally until confirmed disease progression or intolerable adverse event(s).

Drug: Pembrolizumab 200 mg Q3W; Drug: Lenvatinib 20mg QD

Interventions

Pembrolizumab 200 mg Q3W DRUG

The planned dose of pembrolizumab for this study is 200 mg IV every 3 weeks (Q3W). Pembrolizumab will be given for a maximum of 2 years i.e. a total of 35 cycles. Participants who complete study intervention after 2 years of pembrolizumab are eligible for up to 1 year of additional pembrolizumab (second course) upon experiencing disease progression

Arm A

Lenvatinib 20mg QD DRUG

The planned dose of Lenvatinib for this study is 20 mg once daily (QD). Lenvatinib will be taken orally until confirmed disease progression or intolerable adverse event(s).

Arm A

Eligibility Criteria

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

You may qualify if:

• Male or female
• Age \>18 years at the time of signing the informed consent
• Histological confirmation of RCC with a clear-cell component
• Has locally recurrent/metastatic disease (ie, Stage IV per the American Joint Committee on Cancer)
• Patients with RCC with sarcomatoid features are also allowed in this study
• Participants must have progressed on treatment with Pembrolizumab administered as adjuvant treatment. Pembrolizumab treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of Pembrolizumab as adjuvant treatment
• Has demonstrated disease progression after adjuvant Pembrolizumab 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 (as defined in Appendix 4).
• Progressive disease has been documented within 12 months from the last dose of adjuvant Pembrolizumab
• Progressive disease is determined according to iRECIST. This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Male partecipants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose Pembrolizumab and 30 days after last dose of Lenvatinib and agreement to refrain from donating sperm during this period.
• Female partecipants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last, after the last dose of study treatment and agreement to refrain from donating eggs during this period.
• Asymptomatic patients with central nervous system (CNS) metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery. Measurable disease must be present outside the CNS. Before protocol enrollment updated CNS imaging with contrast-enhanced brain CT or brain MRI is required for patients who have received CNS-focal treatment (either by surgery or by RT) ≥ 30 days from initiation of protocol treatment.
• Evaluable International Metastatic RCC Database Consortium (IMDC) risk scores
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline, unless adverse events are clinically non significant in the opinion of the investigator. Participants with endocrine related AEs who are adequately treated with hormone replacement are eligible.

You may not qualify if:

• Treatment with any anti-cancer therapy as first line therapy after adjuvant therapy with pembrolizumab
• Adjuvant treatments other than Pembrolizumab
• Patients with non clear cell RCC
• Symptomatic, untreated, or actively progressing CNS metastases (patient has no history of intracranial hemorrhage or spinal cord hemorrhage; patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment; no evidence of significant vasogenic edema; patient has no ongoing requirement for corticosteroids as therapy for CNS disease but anticonvulsant therapy at a stable dose is permitted; CNS metastases limited to the cerebellum or the supratentorial region, no metastases to the midbrain, pons, medulla, or spinal cord; no evidence of interim progression between completion of CNS- directed therapy and initiation of study treatment)
• Has known leptomeningeal disease or carcinomatous meningitis
• Uncontrolled tumor-related pain symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement; uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures).
• Moderate to severe hepatic impairment (Child-Pugh B or C)
• Symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL, or corrected calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• History of malignancy other than renal carcinoma within 5 years prior to screening, with the exception of in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1. Patients who are receiving single-fraction radiotherapy given for the indication of pain control are eligible
• Active tuberculosis
• Major surgical procedure within 3 weeks prior to initiation of study treatment. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. Minor surgeries (e.g., tumor biopsy, placement of vascular access device) should be performed at least 10 days prior to initiation of study treatment. Patients with clinically relevant ongoing complications from prior surgery are not eligible
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment. Administration of killed vaccines is allowed. Note: please refer to Section 5.3.2 for information on COVID-19 vaccines

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

MeSH Terms

Conditions

Carcinoma, Renal Cell

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

Study Design

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

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 10, 2026

Record last verified: 2026-02