Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Pembrolizumab infusion

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).

Spots Global Cancer Trial Database for blood and tissue sampling