Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Infections

Wounds and Injuries

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Pneumonia

Radiation Pneumonitis

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Central Nervous System Depressants

Other Dietary Supplements

Nivolumab

Pembrolizumab

Atezolizumab

Immune Checkpoint Inhibitors

Tislelizumab

Cisplatin

Immunomodulating Agents

Durvalumab

Benzocaine

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Tannic Acid

For performance status (PS)=0-1 and both lungs V20≤20%, mean lung dose (MLD)≤11 gray(Gy), then the patient should be treated with concurrent chemo-radiotherapy and immunotherapy, and immunotherapy should be given after chemo-radiotherapy to maintain up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with Immune checkpoint inhibitors (ICIs) at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. The chemotherapy regimen will be cisplatin at a dose of 25 mg/m2 once a week for 5-6 cycles. Marketed programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.

For PS=0-1 and 20%\<both lungs V20≤25% or 11Gy\<MLD≤13Gy, radiotherapy alone combined with concurrent immunotherapy, followed by immunotherapy up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.

For PS=2 or 25%\<both lungs V20≤30% or 13Gy\<MLD≤17Gy, radiotherapy alone, followed by immunotherapy for up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. The dosage is recommended according to the drug insert.

Radiotherapy techniques: Volumetric-modulated arc therapy (VMAT) and image guided radiotherapy (IGRT).

Radiotherapy dose: Radical prescription dose of 60 gray (Gy) ± 10%, 2 Gy per session, once a day, 5 days a week.

radiotherapy

Cisplatin 25 mg/m2 once per week for a total of 5-6 cycles. For participants who have not completed 4 cycles of conversion chemotherapy in combination with immunotherapy, the original chemotherapy regimen may also be used, with the total number of chemotherapy cycles not exceeding 6 cycles.

Platinum-Based Drug

Concurrent programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors every 3 weeks during radiotherapy and no more than 3 doses during the course of radiotherapy.

Immunotherapy

All participants will be evaluated within 1-42 days after receiving radiation (chemotherapy). If disease progression does not occur, adjuvant therapy with a PD-1 or PD-L1 inhibitor is continued until disease progression up to 1 year.

Immunotherapeutic Agent

Xu Yujin, PhD

Patients with stage III non-small-cell lung cancer initially evaluated as unresectable are selected for the program, who are remained unresectable after 2-4 cycles of conversion chemotherapy combined with immune checkpoint inhibitors. Investigators will stratify the treatment according to different performance status scores and radiotherapy plan bi-lung receptor volume to evaluate the safety and efficacy of immunotherapy followed by combined radiotherapy.

This is a prospective, real-world cohort study, which aimed to evaluate the safety and efficacy of immunotherapy followed by combined radiotherapy. Participants will be selected and entered into three different cohorts according to different performance status(PS) scores and radiotherapy schedules based on the amount of bilateral lungs treated. Cohort A: PS=0-1 and bilateral lung V20≤20%, mean lung dose(MLD)≤11 gray(Gy), radiotherapy and immunotherapy, followed by immunotherapy for up to 1 year; Cohort B: PS=0-1 and 20%\<bilateral lung V20≤25% or 11 Gy\<MLD≤13 Gy, radiotherapy combined with immunotherapy, followed by immunotherapy for up to 1 year; Cohort C: PS=2 or 25%\<bilateral V20≤30% and 3 Gy \<MLD≤ 17 Gy, radiotherapy alone, followed by immunotherapy for up to 1 year.

Radiotherapy Combined With ICIs as Treatment for LA-NSCLC After Failing Induction Immunochemotherapy

Radiotherapy Combined With Immune Checkpoint Inhibitors (ICIs) as Treatment for Locally Advanced Non-small-cell Lung Cancer After Failing Induction Immuno-chemotherapy: a Prospective, Real-world Cohort Study.

Incidence of grade 2 or higher radiation pneumonitis.

Time from enrolment to disease progression or death from any cause or censored at the last follow-up.

Time from enrolment to death or censored at the last follow-up.

Zhejiang Cancer Hospital

Chief Physician, Department of Thoracic Radiotherapy

Immunotherapy will be administered according to standard of care and reimbursement modalities in Belgium. Targeted agents will be administered according to manufacturer's instructions.

Immunotherapy will be administered according to standard of care and reimbursement modalities in Belgium.

Targeted agents will be administered according to standard of care and reimbursement modalities in Belgium. Targeted agents will be administered according to manufacturer's instructions.

Molecular Target

The purpose of this study is to collect blood samples, as well as tumor tissue for genetic analysis. The collection of samples will allow the creation of a plasma bank. Targeted individuals are cancer patients of all types, treated with immunotherapy or targeted therapy.

Immunotherapy or targeted agents will be administered according to standard of care and reimbursement modalities in Belgium. Targeted agents will be administered according to manufacturer's instructions.

With the aim to identify predictive markers of response to treatment or possible resistance mechanism, the plasma samples and the tumor samples will be used for genetic analysis, for example but not limited to, whole exome sequencing. This may lead to the discovery of some germinal mutations implicated in other diseases than cancer.

The trial will include patients with any type of cancer treated with one of the following regimens after signing of the patient's informed consent:

* I: Molecular targeted agent
* II: Immunotherapy

Prospective Collection of Tumor Biopsy and Plasma Samples From Cancer Patients Treated With Molecular Targeted Therapies or Immunotherapy

Efficacy will be determined in terms of overall responses according to standard practice by the local investigator. Disease and response assessments are defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Overall survival is defined as the time from the date of inclusion to the date of death from any cause or to the date of last follow-up (in exceptional cases where it is impossible to document the date of death). Every effort should be made to document the cause of death.

Progression free survival (PFS) will be measured from the date of inclusion to the date of progression or death, whatever the cause.

Progression will be defined according to the RECIST criteria.

Objective tumor response will be measured according to the RECIST 1.1 criteria.

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

Neoplasm, Residual

Wilms Tumor

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neoplastic Processes

Wilms' Tumor

Vaccines

Molgramostim

Sargramostim

Melphalan

Lenalidomide

Bortezomib

Monatide (IMS 3015)

Proteasome Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Galinpepimut-S (GPS) inoculations are started 12-22 d following autologous stem cell transplantation (ASCT). GPS (1.0 ml of emulsion) is given s.c. on weeks 0, 2, 4, 6, 8, \& 10 (i.e., x 6). Injection sites are pre-stimulated with Sargramostim (GM-CSF; 70 μg) s.c. on d -2 (± 1 d ) \& d 0 of each GPS inoculation. N.B.: during each GPS inoculation, the Sargramostim \& GPS are administered to the same anatomical site. Subjects are observed for \>/= 30 minutes after vaccination. Non-progressing subjects who are clinically stable (no active infection with fevers \& no cardiovascular/respiratory compromise) may receive up to 6 more vaccinations q-month. The use of post-ASCT maintenance therapy with either lenalidomide or bortezomib is allowed starting \>/= 3 months after ASCT.

Preparation of a suspension of liquid vaccine drug product preparation (100 mcg of each peptide x 4 WT1 peptides within the GPS mixture; total weight: 400 mcg) 1:1 v/v with Montanide (oil depot emulsifier) to a total volume of \~1 ml, which is then injected s.c. to the patient. GPS is administered subcutaneously with Montanide adjuvant, with the first dose within 22 days of ASCT with melphalan conditioning (200 mg/sq.m.) and biweekly administration thereafter, for a total of 6 initial doses. Subsequently, patients continued to receive booster GPS administrations every 4 weeks, for an additional set of 6 doses, assuming they remain non-progressors per International Myeloma Working Group (IMW) criteria and are also clinically stable.

WT1 Analog Peptide Vaccine

Granulocyte-macrophage colony-stimulating factor (GM-CSF; Leukine®) is administered s.c. at a dose of 70 μg on day -2 and day 0 of each GPS administration.

Sargramostim (GM-CSF)

IMiD (lenalidomide; 10 mg p.o. daily) OR -in select patients- proteasome inhibitor (bortezomib; 1.3 mg/sq.m. s.c. every 2 weeks) maintenance starting 3-months post auto SCT.

lenalidomide

Guenther Koehne, MD, PhD

David J Chung, MD, PhD

The purpose of this study is to see if the investigator can help the immune system to work against myeloma through the use/administration of a peptide vaccine (immunotherapy agent) directed against the Wilms Tumor 1 (WT1) protein called galinpepimut-S (or GPS, for brief). Because cancer is produced by the patient's own body, the immune system does not easily recognize and fight cancer cells. The immune system needs to be "trained" to do this; the latter goal is accomplished by using a vaccine consisting of selected fragments of the target antigen, in this case, WT1.

This disease has been selected for this study because the WT1 protein is often present in myeloma cells. WT1 is a gene that is involved in the normal development of kidneys and other organs. When the WT1 gene becomes abnormal, it can make proteins involved in the development of cancer, i.e., can acquire the properties of a true "oncogene". This study will determine whether the vaccine against the WT1 antigen (present in malignant plasmacytes) can cause an immune response which is safe, but also able to keep the myeloma from either coming back or progressing.

Key Features:

- This is a Phase 1/2 clinical study conducted in patients with newly diagnosed high-risk multiple myeloma to examine the effects of GPS immunotherapy on clinical and immunobiological indices. The study is titled "A Pilot Trial of a WT1 Analog Peptide Vaccine (Galinpepimut-S) in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation" and is designed as a single-arm, single-institution, open-label study.

Rationale:

- Overexpression of WT1 in multiple myeloma (MM) cells has been demonstrated by immunocytochemistry (IHC) and in HLA-A\*0201 patients by staining with a high-affinity fully human IgG1 mAb (ESK1) specific to the RMFPNAPYL/HLA-A\*0201 complex on malignant plasma cells. WT1 also serves as a target for antigen-specific directly immunizing immunotherapeutic approaches, such as peptide vaccines (in this case, galinpepimut-S), in patients with multiple myeloma. Patients with persistent plasma cell leukemia following CD34+-selected allografts treated with adoptive transfer of donor-derived WT1-specific cytotoxic T cells are capable of achieving long-lasting complete remission (CR) status, thus underscoring the therapeutic potential of activated T-cells specifically immunized against WT1 peptides. The above provide the theoretical basis for the possibility of successful immunization after exposure to a WT1-specific vaccine (such as galinpepimut-S), whereby WT1-sensitized T-lymphocytes (both CD8+ and CD4+) from vaccinated MM could be directed to antigen (WT1) expressed on malignant plasma cells.

Galinpepimut-S (GPS) - Key features:

- GPS is a tetravalent peptide vaccine, consisting of an equiweight mixture of 4 WT1-derived peptides which have been chosen to strengthen antigenicity, but also broaden immunogenicity over a wide range of HLA subtypes, being able to stimulate both CD8+ (MHC Class I)- and CD4+ (MHC Class II)-dependent responses. Of note, 2 of the 4 peptides are heteroclitic, i.e., carry by-design introduced missense mutations, in order to decrease tolerogenicity (as these modified peptides are no longer identified as "self" moieties by the vaccinated host's immune system. GPS contains one heteroclitic peptide (WT1-A1) to stimulate CD8+ responses, two longer native peptides (427 long and 331 long) to stimulate CD4+ responses and one longer heteroclitic peptide (122A1 long) that is capable of stimulating both CD8+ and CD4+ cells (with the CD8-activating shorter sequence/locus 'buried' with the lengthier CD4-activating one). Galinpepimut-S is always mixed in emulsion with the immunological adjuvant Montanide™ and is administered after granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostine; Leukine®) pre-stimulation.

Putative Mechanism of action (MOA) of galinpepimut-S in MM:

- Galinpepimut-S (GPS) is a peptide immunogen of the vaccine type, capable of inducing in the treated host WT1-specific antigenicity and eventual systemic immunogenicity against WT1-expressing deposits of cancerous cells. The above principles are applicable in MM patients treated with this immunotherapeutic. It is very likely that the antigen presenting cell (APC)-CD8-CD4 cross-activating circuits are markedly amplified in subjects receiving galinpepimut-S, leading to specific and direct immunization against WT1 and eventual killing of WT1-expressing malignant plasma cells via activated immunocytes (mainly lymphocytes and natural killer \[NK\] cells). This MOA represents a plausible model for the immunobiological basis of the observed clinical activity of galinpepimut-S against various tumor types (other than MM) tested to-date, and is poised to be applicable in MM as well.

WT1 Analog Peptide Vaccine in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation

A Pilot Trial of a WT1 Analog Peptide Vaccine in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation

The level of induction of T-cell (CD4+ and CD8+) immune responses against WT1 peptides within the galinpepimut-S vaccine mixture - as compared to baseline (t=0; before vaccine administration)- will be measured by intracellular interferon-γ production assay and MHC tetramer analyses - the latter, if available for patient's HLA-type.

The level of induction of T-cell (CD4+ and CD8+) immune responses against WT1 peptides within the galinpepimut-S vaccine mixture - as compared to baseline (t=0; before vaccine administration) - will be measured by intracellular interferon-γ production assay and MHC tetramer analyses - the latter, if available for patient's HLA-type.

From time of registration to the time of documented myeloma progression (as defined by the International Myeloma Working Group \[IMW\] consensus criteria; Kumar S et al. Lancet Oncol. 2016) or subject death.

From time of registration to the time of subject death.

Toxicity will be graded in accordance with Common Toxicity Criteria, version 4.0 (CTCAE 4.0) The only toxicities captured outside of the SAEs reported will be all Grade 1-5 toxicities deemed definitely, probably, or possibly related to the portion of the study. relevant to the active administration of galinpepimut-S.

Protein expression analysis for WT antigens will be done by immunohistochemistry (IHC) as follows: Monoclonal antibodies to CD138/Syndecan, co-express WT1 when staining WT1 mAB 6F-H2 will employed by the study specified research lab on MSKCC S-631.

Sellas Life Sciences Group

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Chemotherapy

target treatment

Surgery

Radiotherapy

Maud Toulmonde, MD

Simone Mathoulin-Pélissier, MD/PhD

Antoine Italiano, MD/PhD

Jean-Yves Blay, MD/PhD

Axel Le Cesne, MD/PhD

The BCB SARCOMES database is a clinical and biological national database dedicated to sarcoma that contains 3 main databases with specific aims: the first is the pathology database (French expert network dedicated to the management of bone sarcomas \[RESOS\] / French expert network dedicated to the pathology of sarcomas \[RREPS\]), dedicated to systematic review of mesenchymal tumor diagnostics nationwide; the second is clinical (RESOS / French expert clinical network for sarcomas \[NETSARC\]), collecting multidisciplinary tumor boards (MDTB) data of patients nationwide, and the third (CONTICABASE / BONE / GIST) is dedicated to collecting patients longitudinal/follow up data, with a focus on treatments of every events, and a catalogue of associated samples.

Primary objectives of BCB-SARCOMES are the following: description of the patterns of care and treatment outcomes, assessment of the prognostic factors of patients' outcomes.

With the financial support of the French National Cancer Institute \[Institut National du cancer \[INCa\]).

National Clinical and Biological Sarcoma Database : An Initiative of the French Sarcoma Group

The "BCB-sarcomes" Database: the Database of the French Sarcoma Group Dedicated to the Collection of Clinical and Biological Data for All Sarcomas

Time from the systemic treatment onset to the next treatment or death due to any cause, whichever comes first. When neither death nor new systemic therapy is observed, TNT is censored at the date of last patient contact.

Interval between diagnosis and the time of death. When death is not observed, OS is censored at the date of last patient contact.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiotherapy Combined With ICIs as Treatment for LA-NSCLC After Failing Induction Immunochemotherapy	NCT06031597	Non-small Cell ...	radiotherapy Platinum-Based ... Immunotherapy Immunotherapeut...	18 Years - 75 Years	Zhejiang Cancer Hospital
Prospective Collection of Tumor Biopsy and Plasma Samples From Cancer Patients Treated With Molecular Targeted Therapies or Immunotherapy	NCT03835520	Cancer	Immunotherapeut... Molecular Targe...	18 Years -	Cliniques universitaires Saint-Luc- Université Catholique de Louvain
WT1 Analog Peptide Vaccine in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation	NCT01827137	Multiple Myelom... Minimal Residua... High-Risk Cance...	WT1 Analog Pept... Sargramostim (G... lenalidomide	18 Years -	Sellas Life Sciences Group
National Clinical and Biological Sarcoma Database : An Initiative of the French Sarcoma Group	NCT03978039	Sarcoma	Chemotherapy Immunotherapeut... target treatmen... Surgery Radiotherapy	-	Institut Bergonié
Radiotherapy Combined With ICIs as Treatment for LA-NSCLC After Failing Induction Immunochemotherapy	NCT06031597	Non-small Cell ...	radiotherapy Platinum-Based ... Immunotherapy Immunotherapeut...	18 Years - 75 Years	Zhejiang Cancer Hospital
National Clinical and Biological Sarcoma Database : An Initiative of the French Sarcoma Group	NCT03978039	Sarcoma	Chemotherapy Immunotherapeut... target treatmen... Surgery Radiotherapy	-	Institut Bergonié

Spots Global Cancer Trial Database for immunotherapeutic agent