NCT04082572

Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers

Neoadjuvant Pembrolizumab for Patients With Mismatch Repair Deficient Locally Advanced Solid Cancers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well pembrolizumab works before surgery in treating patients with mismatch repair deficient solid cancers that have spread to nearby tissue or lymph nodes (locally advanced). Cancer is caused by changes (mutations) to genes (DNA) that control the way cells function, and some of these mutations can cause tumor cells to grow quickly and out of control. Microsatellite instability-high (MSI-H) tumors are made up of cancer cells that have a greater than normal number of genetic markers called microsatellites. These cancers may have defects in the ability to correct mutations that occur when DNA is copied in the cell. Similarly, mismatch repair deficient tumors (dMMR) may have difficulty repairing some type of genetic mutation during cellular replication that may affect tumor's response to cancer therapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety of neo-adjuvant pembrolizumab in patients with locally advanced (unresectable primary cancer or resectable primary cancer with a high chance of recurrence) mismatch repair protein deficiency (dMMR) solid organ tumors by Common Terminology Criteria for Adverse Events (CTCAE) assessed toxicity and post-surgical complication assessment by the Clavien-Dindo classification. II. To assess the rate of complete pathological response for patients who undergo surgical resection following at least 3 doses of neoadjuvant pembrolizumab. SECONDARY OBJECTIVES: I. To quantify the rate of organ sparing at 1 year for all patients treated with one dose of pembrolizumab (intent to treat) and those patients who receive at least 3 doses of neoadjuvant pembrolizumab and decline to undergo surgical resection and opt to continue receiving pembrolizumab for a total of 1 year. II. To assess radiographic tumor response to neoadjuvant pembrolizumab. III. To estimate the relapse-free survival and overall survival in all enrolled participants. IV. To determine the overall rates of pathological response to neoadjuvant pembrolizumab. V. To assess the rate of complete pathological response (intent to treat) for patients who undergo surgical resection following at least 1 dose of neoadjuvant pembrolizumab. EXPLORATORY OBJECTIVE: I. To explore the predictive ability of changes in circulating tumor-derived deoxyriboucleic acid (ctDNA) for efficacy endpoints. II. To determine if total mutational burden correlate with response and extent of benefit from pembrolizumab. III. To correlate pre-treatment tumor samples tumor-immune microenvironment (for example Teffector cell populations; CD4 subsets; T-regulatory populations; B cell populations; dendritic and macrophage populations) with efficacy endpoints. IV. To compare targeted gene expression profiles of immune related genes and genes pertaining to common cancer signaling pathways in pre-treatment samples and also the change in these factors for cases with both pre and on-treatment (i.e. at time of resection) tumor samples of responders (stable disease or radiographic response prior to resection) versus non-responders (progression prior to resection). OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who do not respond to pembrolizumab and stop the treatment after 2 doses may undergo surgery within 6 months. After completion of study treatment, patients are followed up at 30 days, every 6 weeks for 1 year, every 9-12 weeks thereafter.

Conditions

• Locally Advanced Malignant Solid Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2019-10-31
• Primary completion: 2024-11-08
• Completion: 2024-11-08
• First posted: 2019-09-09
• Last updated: 2025-05-13
• Results posted: 2025-05-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study