Renal Cell CarcinomaEarly Phase 1NCT05733715
Neoadjuvant Pembrolizumab and Lenvatinib for Renal Cell Carcinoma
A Early Phase 1 study testing Pembrolizumab infusion and Lenvatinib tablet in people with Renal Cell Carcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This study will evaluate the effect of investigational drugs, pembrolizumab alone or pembrolizumab with lenvatinib, on the immune systems response to kidney cancer when given before and after surgery to remove kidney cancer. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Pembrolizumab infusion and Lenvatinib tablet
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2023to Dec 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of renal cell carcinoma will be enrolled in this study.
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause o Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of child-bearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP OR
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- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Histologically or cytologically confirmed diagnosis of renal cell carcinoma based on newly obtained renal mass core biopsy performed during study screening procedures.
- Renal cell carcinoma with clinical stage cT2 to cT4 based on screening CT or MRI imaging assessment and eligible for surgical resection.
- Note: Patients with regional nodal involvement (cN+) may be included irrespective of clinical T stage, provided disease is deemed "resectable" per treating urologic surgeon.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization.
- Have adequate organ function.
Who cannot join
- A WOCBP who has a positive urine pregnancy test within 24 hours prior to first dose of lenvatinib (ARM A only) or within 72 hours prior to first dose of pembrolizumab (ARMS A and B) (see Appendix 3).
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
- Has had major surgery within 3 weeks prior to first dose of study interventions.
- Has evidence of distant metastatic disease on CT/MRI scans Note: Regional nodal metastases and/or ipsilateral adrenal metastasis are acceptable, if deemed resectable per primary urologic surgeon.
- Has a need for urgent surgical resection per treating investigator
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- Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
- Has a LVEF ≤40%, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
- Subjects having > 1+ proteinuria on urine dipstick testing, unless a 25-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
- Prolongation of QTcF interval to >480 ms.
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
- Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib per investigator discretion
- Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. 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 4 weeks prior to the first dose of study intervention.
- 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 the first dose of study drug.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-invasive urothelial carcinoma, low- or intermediate-risk prostate cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab or lenvatinib and/or any of their excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- 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 (HIV) infection.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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 trial treatment.
- Has had an allogenic tissue/solid organ transplant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Abramson Cancer Center at University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Randomized Pilot Clinical Trial of Neoadjuvant Pembrolizumab +/- Lenvatinib for High Risk Renal Cell Carcinoma
This study will evaluate the effect of investigational drugs, pembrolizumab alone or pembrolizumab with lenvatinib, on the immune systems response to kidney cancer when given before and after surgery to remove kidney cancer.
Read the detailed description
This is a randomized, single-center, unblinded, pilot treatment study to evaluate pembrolizumab with or without lenvatinib as neoadjuvant therapy for RCC planned for surgical nephrectomy. Study objectives include the assessment of immunologic and histologic response measures following neoadjuvant therapy and their association with post-operative clinical outcomes. This trial will generate preliminary data on immune pharmacodynamic outcomes and tumor response for neoadjuvant pembrolizumab +/- lenvatinib and is not powered for comparison between the arms. Up to 33 participants will be enrolled to ensure 30 evaluable patients. Patients who receive neoadjuvant therapy and undergo nephrectomy are considered evaluable. The study will consist of 5 phases: 1) Study Screening; 2) Neoadjuvant Systemic Therapy; 3) Surgical Resection; 4) Adjuvant Systemic Pembrolizumab Therapy; and 5) Post-Treatment Follow-up. The total study participant duration, including participant follow-up across all 4 study phases, will be approximately 60 months.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Pembrolizumab infusion, Lenvatinib tablet
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab infusionDrug
Also called Keytruda
100 mg/ 4mL on Day 1 of each 3- or 6- week cycle (one 3 wk cycle; up to eight 6 wk cycles)
Lenvatinib tabletDrug
Also called Lenvima
10mg and 4mg daily for 21 days
| Study group | Role | What they receive |
|---|---|---|
| A: Pembrolizumab + Lenvatinib | Experimental | Subjects will receive Pembrolizumab + Lenvatinib. Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks. Lenvatinib 20 mg daily will be self-administered PO by subject for 28 consecutive days, beginning Day -7. Receives: Drug: Pembrolizumab infusion; Drug: Lenvatinib tablet |
| B: Pembrolizumab | Experimental | Subject will receive Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks. Receives: Drug: Pembrolizumab infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in frequency of progenitor exhausted CD8 T cells (TEX prog) in peripheral blood during neoadjuvant pembrolizumab +/- lenvatinib and in tumor tissue.
We will apply two 32-parameter spectral flow cytometry panels for phenotypic characterization of paired blood and tumor specimens over the course of multiple timepoints during three distinct treatment periods (Figure 1: Study Schema): 1) before and after neoadjuvant pembrolizumab + lenvatinib (Arm A), and pembrolizumab alone (Arm B); 2) the initial post-operative adjuvant pembrolizumab period; and 3) upon any tumor recurrence.
Measured: Approximately 18-24 months
Secondary outcomes (7)
Change in Ki67 expression
Evaluated as a marker of T cell reinvigoration, in peripheral blood during neoadjuvant pembrolizumab +/- lenvatinib and in tumor tissue.
Measured: Approximately 18-24 months
Percentage Residual Viable Tumor (%irRVT )
Scored as: 0%; 1-10%, 11-20%, 21-30% and increasing 10% increments, per Immune-Related Pathologic Response Criteria (irPRC) after pembrolizumab +/- lenvatinib therapy.
Measured: Approximately 18-24 months
Immune-Related Pathologic Response (irPR)
Defined by %irRVT ≤ 10%.
Measured: Approximately 18-24 months
Brisk TIL
Defined by standard methods.
Measured: Approximately 18-24 months
Toxicities frequency and severity
Score by NCI CTCAE version 5.
Measured: Approximately 18-24 months
Frequency of lenvatinib discontinuation, dose interruption, dose reductions, and dose intensity of lenvatinib during neoadjuvant therapy (observed/expected).
Measured: Approximately 18-24 months
Frequency of surgical delays (>7 days from initially planned operative date), prolonged operative hospitalization (>7 days), or infections (within 30 days of nephrectomy).
Measured: Approximately 18-24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start3 May 2023
- Primary completionApr 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Vivek Narayan, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05733715
- Sponsor's protocol ID
- UPCC 18822
- Other IDs
- IRB#851597
- Status last verified
- Mar 2026
- First submitted
- 30 Jan 2023
- Last updated
- 13 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Pilot Clinical Trial of Neoadjuvant Pembrolizumab +/- Lenvatinib for High Risk Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT05733715
- Acronym / sponsor ID
- UPCC 18822
- Conditions
- Renal Cell Carcinoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 3 May 2023 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 17 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effect of investigational drugs, pembrolizumab alone or pembrolizumab with lenvatinib, on the immune systems response to kidney cancer when given before and after surgery to remove kidney cancer.
Detailed description
This is a randomized, single-center, unblinded, pilot treatment study to evaluate pembrolizumab with or without lenvatinib as neoadjuvant therapy for RCC planned for surgical nephrectomy. Study objectives include the assessment of immunologic and histologic response measures following neoadjuvant therapy and their association with post-operative clinical outcomes. This trial will generate preliminary data on immune pharmacodynamic outcomes and tumor response for neoadjuvant pembrolizumab +/- lenvatinib and is not powered for comparison between the arms. Up to 33 participants will be enrolled to ensure 30 evaluable patients. Patients who receive neoadjuvant therapy and undergo nephrectomy are considered evaluable. The study will consist of 5 phases: 1) Study Screening; 2) Neoadjuvant Systemic Therapy; 3) Surgical Resection; 4) Adjuvant Systemic Pembrolizumab Therapy; and 5) Post-Treatment Follow-up. The total study participant duration, including participant follow-up across all 4 study phases, will be approximately 60 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Pembrolizumab + Lenvatinib | Experimental | Drug: Pembrolizumab infusion, Drug: Lenvatinib tabletSubjects will receive Pembrolizumab + Lenvatinib. Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks. Lenvatinib 20 mg daily will be self-administered PO by subject for 28 consecutive days, beginning Day -7. |
| B: Pembrolizumab | Experimental | Drug: Pembrolizumab infusionSubject will receive Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of renal cell carcinoma will be enrolled in this study.
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib:
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Histologically or cytologically confirmed diagnosis of renal cell carcinoma based on newly obtained renal mass core biopsy performed during study screening procedures.
Key exclusion criteria (27 listed)
- A WOCBP who has a positive urine pregnancy test within 24 hours prior to first dose of lenvatinib (ARM A only) or within 72 hours prior to first dose of pembrolizumab (ARMS A and B) (see Appendix 3).
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
- Has had major surgery within 3 weeks prior to first dose of study interventions.
- Has evidence of distant metastatic disease on CT/MRI scans Note: Regional nodal metastases and/or ipsilateral adrenal metastasis are acceptable, if deemed resectable per primary urologic surgeon.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab infusionAlso: Keytruda100 mg/ 4mL on Day 1 of each 3- or 6- week cycle (one 3 wk cycle; up to eight 6 wk cycles) | Drug | A: Pembrolizumab + Lenvatinib, B: Pembrolizumab |
| Lenvatinib tabletAlso: Lenvima10mg and 4mg daily for 21 days | Drug | A: Pembrolizumab + Lenvatinib |
Primary outcome
Change in frequency of progenitor exhausted CD8 T cells (TEX prog) in peripheral blood during neoadjuvant pembrolizumab +/- lenvatinib and in tumor tissue.
Time frame: Approximately 18-24 months
We will apply two 32-parameter spectral flow cytometry panels for phenotypic characterization of paired blood and tumor specimens over the course of multiple timepoints during three distinct treatment periods (Figure 1: Study Schema): 1) before and after neoadjuvant pembrolizumab + lenvatinib (Arm A), and pembrolizumab alone (Arm B); 2) the initial post-operative adjuvant pembrolizumab period; and 3) upon any tumor recurrence.
7 secondary outcomes
Change in Ki67 expression
Time frame: Approximately 18-24 months
Percentage Residual Viable Tumor (%irRVT )
Time frame: Approximately 18-24 months
Immune-Related Pathologic Response (irPR)
Time frame: Approximately 18-24 months
Brisk TIL
Time frame: Approximately 18-24 months
Toxicities frequency and severity
Time frame: Approximately 18-24 months
Frequency of lenvatinib discontinuation, dose interruption, dose reductions, and dose intensity of lenvatinib during neoadjuvant therapy (observed/expected).
Time frame: Approximately 18-24 months
Frequency of surgical delays (>7 days from initially planned operative date), prolonged operative hospitalization (>7 days), or infections (within 30 days of nephrectomy).
Time frame: Approximately 18-24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Renal Cell Carcinoma
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Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vivek Narayan, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pembrolizumab infusion and Lenvatinib tablet in people with Renal Cell Carcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matt Doyle (215-662-7383, Matthew.Doyle@Pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in frequency of progenitor exhausted CD8 T cells (TEX prog) in peripheral blood during neoadjuvant pembrolizumab +/- lenvatinib and in tumor tissue. (time frame: Approximately 18-24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.