Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

MK-3475 (pembrolizumab) 200 mg flat dose every 21 days

MK-3475

Dung Le, MD

This study will be looking at whether MK-3475 (pembrolizumab) is effective (anti-tumor activity) and safe in patients with MSI (Microsatellite Unstable) negative cancer with a mutator phenotype.

Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)

Phase 2 Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors

Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.

OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 6 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

Disease Control Rate (DCR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

When calculating the incidence of AEs, each adverse event (AE) (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.

Merck Sharp & Dohme LLC

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days

MSI (Microsatellite Unstable) Negative With Mutator Phenotype

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Only 11/12 were evaluable for this outcome

Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype

Overall Survival (OS)

Progression-Free Survival (PFS) in Patients Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors)

Disease Control Rate (DCR)

Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity

Overall Study

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Pleural Effusion

Lung Neoplasms

Pleural Effusion, Malignant

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pleural Diseases

Pleural Neoplasms

Immunomodulating Agents

Immunotherapy was applied for 8 weeks to evaluate the efficacy，The efficacy of immunotherapy was evaluated by imaging, and was evaluated according to RECIST 1.1.

Non-Intervention

Chengzhi Zhou

Multicenter observational study for correlation between tumor mutation burden and immunotherapy efficacy of advanced non-small cell lung cancer with malignant pleural effusion

Method of Research:

1. ⅢB-Ⅳ NSCLC patients, tumor mutation burden (TMB) was tested by the 448 gene panel with pleural effusion and tissue sample, to observed mutation characteristics;Tissue and pleural effusion cell precipitation:TMB (Next generation sequencing, 448 gene panel;Average sequencing depth: above 5000×)
2. The date of blood routine examination(neutrophils to lymphocytes ratio (NLR)) and serological tumor maker of NSCLC were collected before treatment;the The results of Programmed death ligand 1 (PDL1) expression level were collected also;
3. Collected Imaging(CT)and pathological data before treatment;
4. Immunotherapy was applied for 8 weeks to evaluate the efficacy;
5. The tumor mutation burden of pleural effusion was tested again for the patients of hyper-progression after immunotherapy, the mutation characteristics and changes were observed, the molecular mutation change before and after treatment were evaluated, and the correlation with immunotherapy was analyzed.Hyper-progression (HPD) were defined as tumor growth rate excess of 50% compared to baseline CT scans prior to treatment initiation.The patient underwent imaging examination (chest CT or pet-ct) at 2 months (8 weeks) after 3 full doses of immunotherapy drugs.
6. The date of blood routine examination(neutrophils to lymphocytes ratio (NLR)) and serological tumor maker of NSCLC were collected after treatment;
7. Imaging, CT and pathological data of patients after treatment were collected

Multicenter Observational Study of Advanced Non-small Cell Lung Cancer With Malignant Pleural Effusion

Multicenter Observational Study for Correlation Between Tumor Mutation Burden and Immunotherapy Efficacy of Advanced Non-small Cell Lung Cancer With Malignant Pleural Effusion

The relationship between tumor mutation burden and objective response rate in NSCLC patients

The relationship between tumor mutation burden and progression-free survival in NSCLC patients

The relationship between tumor mutation burden and overall survival in NSCLC patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)	NCT04098068	High Tumor Muta... High TMB (Tumor... MSS (Microsatel...	MK-3475	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Multicenter Observational Study of Advanced Non-small Cell Lung Cancer With Malignant Pleural Effusion	NCT04263688	Non-Small Cell ...	Non-Interventio...	18 Years -	Guangzhou Institute of Respiratory Disease

Spots Global Cancer Trial Database for tumor mutation burden (tmb)