Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Topotecan

Atezolizumab

200/Atezolizumab combined with EC regimen Atezolizumab:1200 mg Q3w

100/Atezolizumab combined with chemotherapy Atezolizumab:1200mg Q3w

Other chemotherapy:Irinotecan;topotecan;Enrotinib;Bevacil

Chemotherapy Drugs, Cancer

Li Zhang, PhD

The study is a prospective,multi-center,single arm,real world study to evaluate safety and performance of Atezolizumab plus chemotherapy in patients with extensive-stage small-cell lung cancer,and also to explore potential biomarkers for Immune-related Adverse Events.

In 2018,the results of IMpower 133 were reported on WCLC.Meanwhile,the data was published in NEJM.Atezolizumab combined with carboplatin and etoposide for extensive stage small cell lung cancer was recommended as the first by NCCN guidelines quickly.

Atezolizumab plus chemotherapy was approved by NMPA on Feb 13,2020,making Atezolizumab for 1L ES-SCLC in China.

Real world study can reflect the efficacy and safety of treatment in clinical practice.Based on the research of public database,the prospective cohort study had been reported,but the study based on Chinese patients still left weak point.

Real World Study of Efficacy and Safety of Atezolizumab Plus Chemotherapy in Chinese Patients With ES-SCLC

First-line Atezolizumab Plus Chemotherapy in Patients With Extensive-stage Small-cell Lung Cancer:a Real World,Single Arm,Multicenter,Prospective Study in China

Percentage of participants with Immune-related

Duration of Progression-Free Survival as assessed by the Investigator using Recist v1.1

QLQ C30 Score and EORTC QLQ Lung cancer module (LC13)Score

Beijing Hospital

China-Japan Friendship Hospital

Beijing Chest Hospital

Beijing Chao Yang Hospital

Peking Union Medical College Hospital

Professor,Chief physician

Digestive System Diseases

Symptoms and General Pathology

Esophageal Neoplasms

Recurrence

Esophageal Cancer

Immunomodulating Agents

Chemotherapy± Radiotherapy is used as adjuvant therapy for high risk patients after surgery with or without neoadjuvant therapy.

Chemotherapy + Immunotherapy ± Radiotherapy is used as adjuvant therapy for high risk patients after surgery with or without neoadjuvant therapy.

Chemotherapy± Radiotherapy after surgery

Chemotherapy + Immuonotherapy ± Radiotherapy after surgery

Immunotherapy

Yunpeng Zhao, Doc.

Yunpeng Zhao, doctor

Surgery with or without neoadjuvant therapy is usually used as the treatment for resectable esophageal cancer or esophageal- gastric junction cancer. Patients who have a poor response to neoadjuvant therapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence, to continue with the chemotherapy± radiotherapy is often used in these cases. However, the overall survival is still poor. We designed a prospective randomized controlled tial to study whether immunotherapy could be used with chemotherapy after surgery to improve overall survival. The primary endpoint ofthe study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life.

Ajuvant Chemotherapy and Immunotherapy in Patients With Esophageal, Esophageal- Gastric Junction Cancer

Ajuvant Chemotherapy and Immunotherapy in Patients With Esophageal, Esophageal- Gastric Junction Cancer With or Without Preoperative Chemotherapy With High Risk for Recurrence (N+ and/ or R1)

Rate of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI- CTCAE v5.0)

Quality of Life （KPS or PS or QOL or EORTC QLQ C30）after therapy

The Second Hospital of Shandong University

Skin and Connective Tissue Diseases

Breast Neoplasms

Necrosis

Breast Diseases

Skin Diseases

All patients will receive up to 16 weeks of initial treatment as per study arm assignment, which will include up to 48 LW-02 column-based Immunopheresis® treatments over a 4-month period (up to 3 procedures per week) though treatment can be extended based on certain protocol-specfied conditions. Each patient assigned to the treatment with LW-02 column-based Immunopheresis® will require central vascular access for the procedure. This part is alrady completed.

All patients will receive up to 16 weeks of treatment as per study arm assignment, which will include up to 48 LW-02 column-based Immunopheresis® treatments over a 4-month period (up to 3 procedures per week) though treatment can be extended based on certain protocol-specfied conditions. Each patient will require central vascular access for the procedure. Patients also will receive a low dose chemotherapy regimen administered iv or oraly. Patients treated with combination will be administered their chemotherapy following the first LW-02 column-based Immunopheresis® procedure of each week starting from week 2, assuming first week of study treatment serves as a run-in period confirming good tolerance of Immunopheresis® alone.

Patients who are assigned chemotherapy arm of the study will be treated with low dose chemotherapy alone. The chemotherapy will be administered intravenously or oraly depending on the regimen used.

The Immunoadsorption affinity column, the LW-02 column, uses a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses.

Plasma soluble TNF receptor pulldown

The Immunoadsorption affinity column, the LW-02 column, uses a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses.

In combined treatment arm the Immunopheresis® procedure is combined with low dose chemotherapy to potentially enhancing the latter's cytotoxic effect.

Plasma soluble TNF receptor pulldown + chemotherapy

Low dose chemotherapy will be provided to patient either IV or oraly depending on the regimen used.

Adam Ostrowski,MD Medical Director, International - Immunicom, Inc.

Robert Segal,MD, FACP Chief Medical Officer - Immunicom, Inc.

Prof. Piotr Wysocki, MD, PhD

Alina Wadas

Prof. Tomasz Nowikiewicz, MD, PhD

Tomasz Jankowski, MD, PhD

Gül Başaran, Prof.Dr.

Belma Kurdoğlu Akgün, Msc, PhD

Adam Ostrowski, MD

This is a multicenter, open-label, Phase 1/ 2 study to evaluate the short-term and longer-term safety, tolerability, and effectiveness of Immunopheresis® with the LW-02 column in removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) from plasma of patients with advanced, refractory Breast Cancer (BC) and for disease control when employed as monotherapy, or in combination with a low dose chemotherapy. A low dose chemotherapy will serve as control.

This is a multicenter, open-label, Phase 1/ 2 study to evaluate the short-term and longer-term safety, tolerability, and effectiveness of Immunopheresis® with the LW-02 column in removal of sTNF-Rs from plasma of patients with advanced, refractory BC and for disease control when employed as monotherapy, or in combination with a low dose chemotherapy. A low dose chemotherapy will serve as control.

Part A (n=10 evaluable patients): Overall safety, tolerability, and sTNF-R-removal effectiveness of LW-02 device-based immunopheresis monotherapy conducted 3 times per week for 4 weeks in patients with advanced TNBC. This part is already completed.

Part B/Part B Extension (n = up to 30 evaluable patients): Overall safety, tolerability, and sTNF-Rs-removal effectiveness of LW-02 device-based Immunopheresis® 3 times per week for up to 16 weeks combined with low dose chemotherapy in patients with advanced refractory BC..

Part C (3 treatment arms; n=50 patients per treatment arm): Randomized comparison of overall safety, tolerability, and clinical efficacy effectiveness of (i) Immunopheresis® monotherapy with the LW-02 column 3 times per week for 16 weeks, (ii) or Immunopheresis® in combination with low dose chemotherapy, and (iii) plain low dose chemotherapy.

Safety Endpoints

1. Safety and tolerability - incidence of Adverse Device Effects (ADEs), Serious Adverse Device Effects (SADEs) and Unanticipated Serious Adverse Device Effects (USADEs) related to immunopheresis procedure as well as Adverse Events (AE) and Serious Adverse Events (SAEs).
2. Safety endpoints of special interest - incidence of tumor lysis syndrome, and systemic inflammatory response syndrome.
3. Patient-Reported Outcomes to evaluate health status and Quality of Life (QoL) instruments for patients with BC:

   * Eastern Cooperative Oncology Group (ECOG) status
   * EQ-5D-5L index-based scale
   * EORTC: QLQ-BR23 (breast), and QLQ-C30 (general cancer questionnaire)
   * 6-minute walk test and BORG dyspnea, fatigue scale and hand grip test
   * Nutritional status will be assessed with PG-SGA scale and via laboratory assessments of changes in serum albumin and CRP

Efficacy Endpoints

1. Column efficiency and effectiveness in removal of sTNF-Rs from patient plasma without clinically-meaningful leaching of capture ligand (SC-TNF-α) - change in sTNF-R and TNF-α plasma levels from initiation to the end of each Immunopheresis® procedure, including pre- and post-column measurements, between each treatment, and from baseline to end of a treatment cycle (4 weeks - Part A and B/B-extension, or 16 weeks - Part C).
2. Clinical endpoints - response in tumor burden - progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), duration of clinical benefit (DOCB), time-to-progression (TTP) and overall survival (OS). Serial evaluation of tumor burden/tumor growth is assessed according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

A Multicenter, Open-Label, Three-Part Study

A Study Comparing Immunopheresis® Alone or In Combination With Chemotherapy Versus Chemotherapy Alone in Treatment of Advanced Breast Cancer Patients

A Multicenter, Open-Label, Three-Part Study to Evaluate the Safety and Effectiveness of Immunopheresis With Immunicom's LW-02 Device in Removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) as Well as Clinical Efficacy in Treatment of Patients With Advanced, Refractory Breast Cancer (BC) Alone, or in Combination With Low Dose Chemotherapy Versus Low Dose Chemotherapy.

Column efficiency and effectiveness in removal of sTNF-Rs from patient plasma without clinically-meaningful leaching of capture ligand (SC-TNF-α) - change in sTNF-R and TNF-α plasma levels from initiation to the end of each immunopheresis procedure, including pre- and post-column measurements, between each treatment, and from baseline to end of a treatment cycle (4 weeks - Part A and B, or 16 weeks - Part C).

Safety and tolerability assessment based on adverse event / serious adverse event (AE / SAE) and adverse device / serious adverse device effects (ADE / SADE) reporting using CTCAE/MedDRA coding terms

Incidence of tumor lysis syndrome and systemic inflammatory response syndrome.

A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Overall Survival (OS). Overall survival ( OS ) is defined as the time from randomization to death from any cause, is adirect measure of clinical benefit to a patient.

A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Progression Free Survival (PFS) Progression-free survival ( pfs ) is defined as time from randomization until firstevidence of tumour progression or until death from any cause, whichever comes first.

A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Disease Control Rate (DCR) Overall response rate (ORR) is defined as the proportion of patients who have a partialor complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity.In contrast, disease control rate is a composite of ORR and stable disease and is useful to measure the efficacy oftherapies that have tumoristatic effects rather than tumoricidal effects.

Nutritional status will be assessed with PG-SGA scale and via laboratory assessments of changes in serum albumin and CRP concentration. The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) scale will be used. The Scored PG-SGA©includes the four patient-generated historical components (Weight History, Food Intake, Symptoms and Activities andFunction - also known as the PG-SGA Short Form©), the professional part (Diagnosis, Age, Metabolic stress, andPhysical Exam), the Global Assessment (A = well nourished, B = moderately malnourished or suspected malnutrition,C = severely malnourished) and the total numerical score

Eastern Cooperative Oncology Group (ECOG) scale describes patient's functioning in terms of ability to care forthemselves, daily activity, and physical ability (walking, working). The scale grades 0 to 5 (0=fully active while 5=dead).

EQ-5D-5L scale to assess: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimensionhas 5 levels:from no problems to extreme problems.

EORTC-QLQ-C30 scale measures cancer patients' physical, psychological and social functions. The EORTC QLQ-C30 comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, fivefunctioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. All of the scales and single-item measures range in score from 0 to 100.Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better stateof the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. aworse state of the patient).

EORTC: QLQ-BR23 (breast) measuring the quality of life in patients with breast cancer. Each dimension in the scale has four response levels from not at all (1) to very much (4).

The physical performance assessment will be measured with 6-minute walk test (6MWT). 6MWT meassures the distance patient covers when walking in a regular pace in standardized condition. The longerdistance is expected in patients who improve while the poor patient performance and capability, the shorter distancewill be measured.

The muscle performance assessment will be measured hand grip test. The purpose of this test is to measurethe maximum isometric strength of the hand and forearm muscles. The participant will be asked to squeeze thedynamometer as hard as possible with each of his or her hands in a standing position. The subject squeezes thedynamometer with maximum isometric effort, which is maintained for about 5 seconds. Results for left and right handseparately are recorded in kilograms.

Immunicom Inc

Carcinoma, Non-Small-Cell Lung

Micronutrients

Hematinics

Anti-Infective Agents

Amino Acids

Vitamins

Osimertinib

Gemcitabine

Vinorelbine

Carboplatin

Immune Checkpoint Inhibitors

Pemetrexed

Pembrolizumab

Docetaxel

Cisplatin

Nivolumab

Mitomycins

Mitomycin

Afatinib

Vinblastine

Crizotinib

Tyrosine Kinase Inhibitors

Alectinib

Erlotinib Hydrochloride

Gefitinib

Ceritinib

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Protein Kinase Inhibitors

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Tyrosine

Folinic Acid

Folate

Vitamin B9

Patients over 18 years of age with a diagnosis of non-small cell lung cancer and being received PD-1 inhibitors as a second line treatment from cytotoxic chemotherapy or as a third line for those received tyrosine kinase inhibitors as a first line, from August 2017 (the first month PD-1 inhibitors were reimbursed in South Korea) to September 2018.

Patients over 18 years of age with a diagnosis of non-small cell lung cancer and being received cytotoxic chemotherapy or tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) from August 2017 to September 2018. Each patient switching to PD-1 inhibitor will be matched to three reference standard chemotherapy users.

PD-1 inhibitors are a group of checkpoint inhibitors being developed for the treatment of cancer. PD-1 and PD-L1 are both proteins present on the surface of cells. Immune checkpoint inhibitors such as these are emerging as a front-line treatment for several types of cancer. The investigators will include nivolumab, pembrolizumab, and atezolizumab as PD-1 inhibitors as these drugs are reimbursed by health authority of South Korea.

PD-1 inhibitor

Chemotherapy is a type of pharmacotherapy for cancer, that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. The investigators will include cytotoxic chemotherapy and tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors).

Yeon-Hee Baek

Ju-Young Shin, PhD

The objective of our study is to assess the risk of immune-related adverse events associated with PD-1 inhibitors use compared to standard chemotherapy use in patients with non small cell lung cancer, using nationwide healthcare database.

This observational, retrospective cohort study will evaluate the risk of immune-related adverse events associated with PD-1 inhibitors use compared to standard chemotherapy use in patients with non small cell lung cancer, using nationwide healthcare database. PD-1 inhibitors will be defined as nivolumab, pembrolizumab, and atezolizumab. Standard chemotherapy will be defined as cytotoxic chemotherapy or tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors). The investigators will assess exposure on the cohort entry using the intention-to-treat approach with the 6-month exposure risk window from the first PD-1 inhibitor prescription to avoid bias from informative censoring. Immune-related adverse events will be defined by using pre-specified algorithms using diagnosis and corticosteroid prescription records (high dose of oral corticosteroids, defined as ≥ 30 mg/day, or systemic corticosteroid injection) to reduce outcome misclassification. The investigators will use a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and 95% confidence intervals (CI). The model will be adjusted for pre-existing autoimmunity, history of lung cancer surgery, radiation therapy, tyrosine kinase inhibitor use, and previous systemic corticosteroid use. All analyses will be undertaken using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).

PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study

The ratio of hazard rates of immune-related adverse events in PD-1 inhibitor users vs. standard chemotherapy users

The ratio of hazard rates of eleven subdivided organ-specific immune-related adverse events (pulmonary, endocrine, cardiovascular, gastrointestinal, hepatic, muscluoskeletal, neurological, ocular, renal, skin, and hematologic) in PD-1 inhibitor users vs. standard chemotherapy users

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Real World Study of Efficacy and Safety of Atezolizumab Plus Chemotherapy in Chinese Patients With ES-SCLC	NCT04663438	Extensive-stage...	Chemotherapy Dr...	18 Years - 80 Years	Peking Union Medical College Hospital
Ajuvant Chemotherapy and Immunotherapy in Patients With Esophageal, Esophageal- Gastric Junction Cancer	NCT04688801	Esophageal Canc... Gastroesophagea... Immunotherapy Adjuvant	Chemotherapy Dr... Immunotherapy	25 Years - 80 Years	The Second Hospital of Shandong University
A Study Comparing Immunopheresis® Alone or In Combination With Chemotherapy Versus Chemotherapy Alone in Treatment of Advanced Breast Cancer Patients	NCT04004910	Advanced Breast...	Plasma soluble ... Plasma soluble ... Chemotherapy Dr...	18 Years -	Immunicom Inc
Ajuvant Chemotherapy and Immunotherapy in Patients With Esophageal, Esophageal- Gastric Junction Cancer	NCT04688801	Esophageal Canc... Gastroesophagea... Immunotherapy Adjuvant	Chemotherapy Dr... Immunotherapy	25 Years - 80 Years	The Second Hospital of Shandong University
Real World Study of Efficacy and Safety of Atezolizumab Plus Chemotherapy in Chinese Patients With ES-SCLC	NCT04663438	Extensive-stage...	Chemotherapy Dr...	18 Years - 80 Years	Peking Union Medical College Hospital
Real World Study of Efficacy and Safety of Atezolizumab Plus Chemotherapy in Chinese Patients With ES-SCLC	NCT04663438	Extensive-stage...	Chemotherapy Dr...	18 Years - 80 Years	Peking Union Medical College Hospital
Ajuvant Chemotherapy and Immunotherapy in Patients With Esophageal, Esophageal- Gastric Junction Cancer	NCT04688801	Esophageal Canc... Gastroesophagea... Immunotherapy Adjuvant	Chemotherapy Dr... Immunotherapy	25 Years - 80 Years	The Second Hospital of Shandong University
PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study	NCT04115410	Carcinoma, Non-... Immune-Related ...	PD-1 inhibitor Chemotherapy Dr...	18 Years -	Sungkyunkwan University

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