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Neoadjuvant Pembrolizumab and Lenvatinib for Renal Cell Carcinoma

ConditionRenal Cell Carcinoma
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAbramson Cancer Center at Penn Medicine

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

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.

Is not a WOCBP OR

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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)

  • Lenvatinib tablet

    Drug

    10mg and 4mg daily for 21 days

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: A: Pembrolizumab + LenvatinibExperimental treatment 2 interventions
Group B: B: PembrolizumabExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
Approximately 18-24 months

Secondary outcomes

1

Change in Ki67 expression

Evaluated as a marker of T cell reinvigoration, in peripheral blood during neoadjuvant pembrolizumab +/- lenvatinib and in tumor tissue.

Time frame
Approximately 18-24 months
2

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.

Time frame
Approximately 18-24 months
3

Immune-Related Pathologic Response (irPR)

Defined by %irRVT ≤ 10%.

Time frame
Approximately 18-24 months
4

Brisk TIL

Defined by standard methods.

Time frame
Approximately 18-24 months

Other outcomes

1

Disease-free survival (DFS)

as defined by time from surgery to first documented disease recurrence or death due to any cause, or last date that documents recurrence-free status.

Time frame
Approximately 60 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Abramson Cancer Center at Penn Medicine

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Source ClinicalTrials.gov
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