Neoadjuvant Pembrolizumab and Lenvatinib for Renal Cell Carcinoma

NCT05733715 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: UPCC 18822IRB#851597
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Approximately 18-24 months

Secondary Outcomes (7)

• Change in Ki67 expression

  Approximately 18-24 months

• Percentage Residual Viable Tumor (%irRVT )

  Approximately 18-24 months

• Immune-Related Pathologic Response (irPR)

  Approximately 18-24 months

• Brisk TIL

  Approximately 18-24 months

• Toxicities frequency and severity

  Approximately 18-24 months

Other Outcomes (1)

• Disease-free survival (DFS)

  Approximately 60 months

Study Arms (2)

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.

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.

Drug: Pembrolizumab infusion

Interventions

Pembrolizumab infusion DRUG

100 mg/ 4mL on Day 1 of each 3- or 6- week cycle (one 3 wk cycle; up to eight 6 wk cycles)

Also known as: Keytruda

A: Pembrolizumab + Lenvatinib; B: Pembrolizumab

Lenvatinib tablet DRUG

10mg and 4mg daily for 21 days

Also known as: Lenvima

A: Pembrolizumab + Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Abramson Cancer Center at University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

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 Officials

• Vivek Narayan, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matt Doyle

CONTACT

215-662-7383; Matthew.Doyle@Pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 17, 2023
• Study Start: May 3, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)