Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Carcinoma

Microsatellite Instability

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Genomic Instability

Immunohistochemical analysis was performed for Microsatellite Instability (MSI) status of colorectal tumors tissue.

Molecular analysis for Microsatellite Instability (MSI) status was performed using immunohistochemistry (IHC). IHC now recognized as an approved method to highly precision predict MSI in colorectal cancer.

Microsatellite instability analysis

Taygun Gülşen, MD

In this study, we aimed to identify the different histopathological features of tumors with microsatellite instability (MSI) compared to microsatellite stable (MSS) in patients who underwent surgery for colorectal cancer. We also planned to determine how MSI affects prognostic parameters.

According to Global Cancer Statistics, higher than 1.9 million new cases of colorectal cancer (CRC) and 935,000 deaths are estimated to occur in 2020, representing about one in 10 cancer cases and deaths. Overall, it ranks third in colorectal incidence but second in mortality.

In CRC evolution, the acquisition of genomic instability is a critical point, and there are at least two different pathways in the pathogenesis of CRC: the chromosomal instability (CIN) pathway (85%) and the microsatellite instability (MSI) pathway (15%).

Microsatellite instability (MSI) is a phenotype that occurs due to a malfunction in the DNA repair mechanism and is seen in approximately 15% of colorectal cancers (CRCs). CRCs with MSI have different clinical features, such as a tendency to settle in the proximal colon, poor differentiation, and more lymphocytic infiltration in the tumor. It has been shown that CRCs with MSI have a better prognosis and respond differently to chemotherapy than CRCs with microsatellite stable (MSS).

We aimed to evaluate the different histopathological features of tumors with MSI compared to MSS in patients who underwent surgery for colorectal cancer. We also planned to determine how MSI affects prognostic parameters such as mortality rate, recurrence, disease-free survival, cancer-specific survival, and overall survival.

Microsatellite Instability in Colorectal Cancers

Clinicopathological Outcomes of Microsatellite Instability in Colorectal Cancer

Overall survival is defined as the time interval from the time of primary operation to the date of all-cause death or the last follow-up.

Disease-Free Survival is defined as the time interval from the time of primary operation to disease recurrence or death.

Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey

MD, General Surgeon

Rectal Neoplasms

All Drugs and Chemicals

Immunomodulating Agents

neoadjuvant chemoradiation therapy +immunotherapy

neoadjuvant chemoradiation therapy +xintilimab injection 200mg/3week 4cycle

xintilimab injection

Control

Wei Zhang

At present, there are no relevant studies or reports on the effect of neoadjuvant chemoradiation therapy combined with immunotherapy for MSS ultra-low rectal cancer. Studied in this paper combin neoadjuvant chemoradiation with immune therapy, carry out "Multicenter prospective randomized clinical trial of neoadjuvant chemoradiation therapy combined with immunotherapy for MSS ultra-low rectal cancer" in order to provide a high-level evidence-based medical evidence for ultra-low rectal cancer treatment and improve ultra-low rectal cancer diagnosis and treatment effect.

Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer

Multicenter Prospective Randomized Clinical Trial of Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer

IPD would be available upon reasonable request.

Rate of patients who achieve clinical complete response

Rate of patients who achieve organ preservation

Rate of patients who achieve anus preservation

DFS was defined as the duration from the date of randomization to the date of the first recurrence (local, distant, or mixed) or death.

OS was calculated from the date of randomization.

The QoL was assessed by EORTC QOL Core Questionnaire.

Changhai Hospital

Chief physician, professor

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Neoplasm Metastasis

Stomach Neoplasms

Esophageal Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Head and Neck Neoplasms

Endometrial Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Stomach Diseases

Uterine Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Immune Checkpoint Inhibitors

Pembrolizumab

Antineoplastic Agents, Immunological

All participants will receive NC410 (IV) and pembrolizumab (IV) according to the treatment schedule until a reason for treatment discontinuation is reached.

NC410 will be given intravenously (IV) every 2 weeks

NC410

Pembrolizumab 400mg will be given IV every 6 weeks.

pembrolizumab

Associate Director Clinical Operations at NextCure, Inc.

Director of Clinical Research

Julie A Klinker

Sudhir Manda, MD

Jennifer R Hege

Sujatha Nallapareddy, MD

Amy Pajik

Douglas Flora, MD

Nicole Perry

Marc Matrana, MD

Research Referral Office

Eric Christenson, MD

Chelsea McCabe

Martin Gutierrez, MD

Kvitka Peczonczyk

Emese Zsiros

Christine Vollmer

Davendra Sohal, MD

Martha Cruz

Syed Kazmi, MD

Jonathan B Huntzinger

Thomas Hutson, DO

Siqing Fu, MD

Epp Goodwin

Daruka Mahadevan, MD

Debora E Lind

Sridhar Beeram, MD

Stephanie Van Bebber, MSc

Raymond C Wadlow, MD

Carrie Friedman

Alexander Spira, MD

Susan Papenfuse, CRC,RN

David P Cosgrove, MD

Han Myint, MD

This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors

A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors

A Phase 1b/2, Open-Label, Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab for Participants With Advanced Unresectable and/or Metastatic Immune Checkpoint Inhibitor (ICI) Refractory Solid Tumors or ICI Naïve MSS/MSI-Low Solid Tumors

Frequency, duration, and severity of treatment-emergent adverse events (AEs)

A mTPI design will be utilized to determine the RP2D of NC410

Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Merck Sharp & Dohme LLC

NextCure, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Microsatellite Instability in Colorectal Cancers	NCT05162248	Colorectal Canc... Colorectal Carc... Microsatellite ... Microsatellite ... Microsatellite ...	Microsatellite ...	18 Years - 100 Years	Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey
Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer	NCT05215379	Neoadjuvant Che... Rectal Cancer Immunotherapy Microsatellite ...	xintilimab inje... Control	18 Years - 75 Years	Changhai Hospital
A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors	NCT05572684	Advanced or Met... Microsatellite ... Microsatellite ... Microsatellite ... Ovarian Cancer Gastric Cancer Colo-rectal Can... Esophageal Canc... Endometrial Can... Head Neck Cance... Cervical Cancer Lung Cancer	NC410 pembrolizumab	18 Years -	NextCure, Inc.
Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer	NCT05215379	Neoadjuvant Che... Rectal Cancer Immunotherapy Microsatellite ...	xintilimab inje... Control	18 Years - 75 Years	Changhai Hospital

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