Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

Subject will receive Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks.

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

Pembrolizumab infusion

Lenvatinib tablet

Matt Doyle

Vivek Narayan, MD

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.

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.

Neoadjuvant Pembrolizumab and Lenvatinib for Renal Cell Carcinoma

Randomized Pilot Clinical Trial of Neoadjuvant Pembrolizumab +/- Lenvatinib for High Risk Renal Cell Carcinoma

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.

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.

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

Scored as: 0%; 1-10%, 11-20%, 21-30% and increasing 10% increments, per Immune-Related Pathologic Response Criteria (irPRC) after pembrolizumab +/- lenvatinib therapy.

Merck Sharp & Dohme LLC

Abramson Cancer Center at Penn Medicine

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Arm 1 will receive radiotherapy on day -14 and pembrolizumab on day -7. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.

Arm 2 will receive pembrolizumab on day -14 and radiotherapy on day -7. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.

Arm 4 will not receive any study treatment. Subjects will undergo surgery on day 0 and follow a preoperative (Day 0) and postoperative blood (Day 30) and tissue (Day 0) sampling schedule.

Radiation boost (RT) 7 Gy x 1 fraction on Day -14/Day -7 (arm 1) or Day -7/Day -14

Hypofractionated radiotherapy

Pembrolizumab infusion flat dosing 200 mg delivered over 30 minutes.

Blood will be collected for laboratory studies and complete correlative studies to examine how the subject's immune system is responding to treatment. On day 0, samples of tumor and any lymph nodes removed from armpit will be analyzed by the UPenn Department of Pathology according to standard practice.

Blood and tissue sampling

Julia C Tchou, MD

Michelle Gelman

Julia Tchou, MD, PhD

Carolina Reyes, BS

The primary objective is to determine the feasibility of combining pembrolizumab with a single fraction radiation boost in patients with early/ operable breast cancer. The secondary objectives are to assess clinical response on pre- and post-treatment clinical, imaging, and histology exams, and to assess immune response on pre and post treatment blood and tissue samples by tracking change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes. A clinically significant partial response is defined as \>30% tumor shrinkage post-clinical trial intervention.

The study has four arms. Arms 1 and 2 differ by the order of radiation boost and pembrolizumab administration. A minimum of 6 patients will be enrolled in the safety run-in portion of the study. The Phase 2 portion of the study will include Arm 3 (pembrolizumab only arm). An estimated 27 participants will be enrolled or until futility of Arm 3 is reached. Continuation of enrollment in Arms 1 or 2 will be contingent to funding availability. Arm 4 represents our control arm in which patients will follow usual care but will be consented for blood/tissue collection using a separate protocol (Penn IRB 801539).

BreastVAX: Radiation Boost to Enhance Immune Checkpoint Blockade Therapy

Preoperative Use of Radiation Boost to Enhance Effectiveness of Immune Checkpoint Blockade Therapy in Operable Breast Cancer

Feasibility is defined as patient tolerability of the investigational treatment and no excessive delay in surgery in our participants. The interval to breast-conserving surgery and mastectomy was based on review of our records in patients undergoing breast cancer surgery in 2016. The average time to breast conservation surgery is 24.3 days (80% between 9 and 51 days) and for mastectomy with reconstruction 41.6 days (80% between 10 and 67 days).

Evaluate clinical response using the following assessments:

1. Clinical breast exam
2. Breast ultrasonography (US) imaging (optional) for tumor dimension changes.
3. Histology (pathology) exams. Pathologic response is assess histologically on post-treatment tumor tissues. A major pathologic response will be defined as \<10% viable invasive tumor in treated. A clinically significant partial response is defined as \>30% tumor shrinkage post-clinical trial intervention.

Assess immune response on pre- and post-treatment blood and tissue samples This study will track change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes (TIL).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Pembrolizumab and Lenvatinib for Renal Cell Carcinoma	NCT05733715	Renal Cell Carc...	Pembrolizumab i... Lenvatinib tabl...	18 Years -	Abramson Cancer Center at Penn Medicine
BreastVAX: Radiation Boost to Enhance Immune Checkpoint Blockade Therapy	NCT04454528	Breast Cancer	Hypofractionate... Pembrolizumab i... Blood and tissu...	18 Years -	Abramson Cancer Center at Penn Medicine

Spots Global Cancer Trial Database for pembrolizumab infusion