Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma, Transitional Cell

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Atezolizumab

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immune Checkpoint Inhibitors

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

LYMPHODEPLETION: Patients receive cyclophosphamide IV and fludarabine IV on days -4, -3, and -2 before each T-cell infusion.

T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve weeks after first T-cell infusion, patients with progressive disease and non-persisting transgenic TCR T cells may receive a second T-cell infusion.

In the Phase 2 portion of the study, atezolizumab will be administered as standard of care beginning 24-72 hours after T-cell infusion. Atezolizumab will be given IV every 3 weeks for at least 1 year in the absence of disease progression or unacceptable toxicity. An alternative PD1 inhibitor may be substituted if atezolizumab (preferred) is not available.

MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells

PD1 Inhibitor

Michael Schweizer

This phase I/II trial investigates the side effects of genetically engineered cells called FH-MagIC TCR-T cells and how well they work with atezolizumab in treating patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer that has spread to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize MAGE-A1, a protein on the surface of tumor cells. These MAGE-A1-specific T cells may help the body's immune system identify and kill MAGE-A1 tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FH-MagIC TCR-T cells with atezolizumab may help treat patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer.

OUTLINE:

This is a phase I, dose escalation study of FH-MagIC TCR-T cells followed by a phase II study.

LYMPHODEPLETION: Patients receive cyclophosphamide intravenously (IV) and fludarabine IV on days -4, -3, and -2 before each T-cell infusion.

T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve weeks after first T-cell infusion, patients with progressive disease and non-persisting transgenic TCR T cells may receive a second T-cell infusion.

In the Phase 2 portion of the study, atezolizumab will be administered as standard of care beginning 24-72 hours after T-cell infusion. Atezolizumab will be given IV every 3 weeks for at least 1 year in the absence of disease progression or unacceptable toxicity. An alternative PD1 inhibitor may be substituted if atezolizumab (preferred) is not available.

After completion of study treatment, patients are followed up annually for 15 years after final infusion of FH-MagIC TCR-T.

Genetically Engineered Cells (MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells) and Atezolizumab for the Treatment of Metastatic Triple Negative Breast Cancer, Urothelial Cancer, or Non-small Cell Lung Cancer

ATTAMAGE-A1.: Phase I/II Study of Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity MAGE-A1-Specific T-Cell Receptor (TCR) Combined With Atezolizumab in Patients With Metastatic MAGE-A1 Expressing Cancer

Lesions will be separately tracked but response determined in totality. As indicated, patient must have at least one trackable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response will be a defined as best overall response by RECIST 1.1. A Complete Response will be defined as total regression of all tumors, a Partial Response as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and Progressive Disease as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter. If the disease does not fall in either category it will be considered Stable Disease (RECIST v1.1 criteria).

Results will be reported by sample for the single treated patient. Patient samples were tested using a WPRE assay showing transgenic T cells in blood. This was detected by qPCR.

Outcome will be reported as a count of participants that displayed transgenic T cells in their tumor tissue after treatment. This was assessed by WRPE staining and scRNA sequencing. Unfortunately, no transgenic cells were detected on the one treated patient's tumors.

Outcome will be reported as a count of participants that were alive as the 1 year post infusion timepoint and also had not experienced progression at that timepoint.

Outcome will be reported as a count of participants that were alive at the 1 year post infusion timepoint.

Evaluated by immune-related RECIST criteria. Outcome will be reported as a count of participants that experienced a Complete Response or Partial Response per RECIST criteria. A complete response (CR) will be defined as total regression of all tumors, a Partial Response as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and Progressive Disease as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter. If the disease does not fall in either category it will be considered Stable Disease (RECIST v1.1 criteria).

SignalOne Bio, Inc.

Fred Hutchinson Cancer Center

Associate Professor

LYMPHODEPLETION: Patients receive cyclophosphamide IV and fludarabine IV on days -4, -3, and -2 before each T-cell infusion.

T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve weeks after first T-cell infusion, patients with progressive disease and non-persisting transgenic TCR T cells may receive a second T-cell infusion.

In the Phase 2 portion of the study, atezolizumab will be administered as standard of care beginning 24-72 hours after T-cell infusion. Atezolizumab will be given IV every 3 weeks for at least 1 year in the absence of disease progression or unacceptable toxicity. An alternative PD1 inhibitor may be substituted if atezolizumab (preferred) is not available.

Atezolizumab: Given IV

Cyclophosphamide: Given IV

Fludarabine: Given IV

MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells: Given IV

PD1 Inhibitor: Given IV

Treatment (FH-MagIC TCR-T Cells, Atezolizumab)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Damian Green

Count of Participants That Experienced Treatment-related Unexpected Grade 3 or Higher Adverse Events

Best Overall Response

BU712PRETX

BU712I1D000

BU712I1D001

BU712I1D003

BU712I1D007

BU712I1D014

BU712I1D021

BU712I1D028

BU712I1D056

BU712I1D180

BU712I2D03

BU712I2D07

BU712I2D14

BU712I2D21

BU712I2D28

BU712I2D56

BU712I2D84

Peripheral Blood Concentration of Infused Transgenic T Cells Over Time

Participants That Displayed Transgenic T Cells in Tumor Tissue

Progression-free Survival

Overall Survival

Objective Response Rates

Overall Study

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Azacitidine

Decitabine

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Antimetabolites

Enzyme Inhibitors

Patients will be administered Camrelizumab(SHR-1210) at D1 and D15 and decitabine at D1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity.

Camrelizumab(SHR-1210)

Kai Xue

Hongming Zhu

Junmin Li

This is an open-label, single arm, phase 2 study to evaluate efficacy and safety of PD1 inhibitor Camrelizumab(SHR-1210) combined with DNA methyltransferase inhibitor decitabine in elderly patients with relapse and refractory acute myeloid leukemia.

In this single-center, open-label, nonrandomized, no control, prospective clinical trial, 29 relapsed or refractory acute myeloid leukemia patients will be enrolled. Patients will be administered Camrelizumab(SHR-1210) at D1 and D15 and decitabine at D1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity.

Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia

Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia : An Open-Label, Single-Arm, Phase 2 Study.

CR, CRi, and morphologic leukemia-free state (MLFS)

Blast and promyelocytic leukemia less than 5% in bone marrow

PFS is defined from the date of entry on study until disease progression, including treatment failure, relapse from CR, or death from any causes.

OS is defined for patients entering the study as time to death of all causes.

To evaluate overall survival rate at 6 months from study entry.

To evaluate overall survival rate at 12 months from study entry.

Assessed according to the Common Terminology Criteria for Adverse Events Version 4.03.

Shanghai Jiao Tong University School of Medicine

Director of Department of Hematology

Digestive System Diseases

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Pharmaceutical Solutions

Bone Density Conservation Agents

Micronutrients

Vitamins

Pembrolizumab

Vitamin D

Cholecalciferol

Vitamin A

Retinol palmitate

Ergocalciferols

Hormones

Calcium

Calcium, Dietary

Trace Elements

Vitamin D3

Calciferol

Retinol

Ergocalciferol

Vitamin D2

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

pembrolizumab 200 mg IV q 3 weeks \& placebo- normal saline IV 3 xs per week

paricalcitol

placebo

Daniel D Von Hoff, MD, FACS

Chemotherapy regimens for pancreatic cancer can now stabilize a patient's cancer and/or place some patients in remission or partial remission. The challenge now is to find options for maintenance therapies that will improve survival and allow continued benefits with minimal toxicities and inconvenience to the patients. This study will determine the effects of one possible maintenance regimen.

The study is being conducted to determine the effects that pembrolizumab with or without the addition of paricalcitol may have on pancreatic cancer. Half of the patients will be randomized to receive pembrolizumab + paricalcitol and half to receive pembrolizumab + placebo.

Pembrolizumab (also known as Keytruda®), which is approved in the USA and some other countries, is available by prescription to treat several different cancers, but has not been approved to treat pancreatic cancer. Pembrolizumab helps the body detect and fight cancer by making cancer cells more vulnerable to attack by the body's immune system. This medication binds to and lessens the action of specific parts of cells in the body's immune system, which act to modulate or balance the immune response. By decreasing this modulation of the immune response, the body's own system may be better able to fight the cancer. Pembrolizumab is known as an immune checkpoint inhibitor.

It is thought that the effect of pembrolizumab could possibly be strengthened by the addition of paricalcitol, which is a form of vitamin D. Paricalcitol may make the cells in the immune system more sensitive to the activity of pembrolizumab and could make the local environment hostile to the cancer cells. Both activities could be effective against cancer growth.

Paricalcitol (also known as Zemplar®) is used to treat high levels of parathyroid hormone and prevent bone loss in patients with advanced kidney disease. Paricalcitol is not approved by the FDA for the treatment of advanced pancreatic cancer.

The effects of the study drugs will be assessed by repeated radiological imaging (CT scans), incidence of adverse reactions, and survival rates.

Participants will also be asked to provide biological specimens for the study team to measure cellular changes. This will include fecal matter (stool), blood, and tumor tissue.

The Food and Drug Administration (FDA) has determined that this study meets the requirements for Investigational New Drug (IND) Exemption.

This is a double-blind, randomized, placebo-controlled phase II trial with the identity of the treatment unknown to the patients, investigators, and the Sponsor.

A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer

A SU2C Catalyst ® Randomized Phase II Trial of the PD1 Inhibitor Pembrolizumab With or Without a Vitamin D Receptor Agonist Paricalcitol in Patients With Stage IV Pancreatic Cancer Who Have Been Placed in Best Possible Response

Difference in disease progression according to RECIST 1.1 and iRECIST criteria

Patient compliance rate of completing the PPCB application was calculated by the total percentage of completed questionnaires over expected questionnaires across all participants.

Improvement in symptoms as recorded by the Patient Personalized Clinical Benefit (PPCB)

Differences in tumor and/or tissue texture on CT scans between the two treatment arms

Differences in gut microbial communities within and between fecal samples using alpha and beta diversity metrics based on 16S rRNA sequencing

Progression Free Survival (PFS) defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) survival in the absence of death or progressive disease which is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

All adverse events occurring on or after Cycle 1/day 1through 30 days after the last dose of trial treatment will be summarized by body systems and per grade according to NCI-CTCAE Version 4.

Duration of survival will be defined as the time from initial treatment (cycle1/day1) until death. Overall survival will be estimated for each arm using a Kaplan-Meier estimate.

Mutational landscapes, transcriptional programs in tumor tissue

Identify cellular VDR targets in the immune microenvironment

Stand Up To Cancer

Merck Sharp & Dohme LLC

Translational Genomics Research Institute

Participants with multiple events for a given AE term were counted only once for each AE term. If the same AE term was reported more than once for a participant, only the AE term with the highest grade was included.

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

Pembrolizumab & Paricalcitol

pembrolizumab 200 mg IV q 3 weeks \& placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Pembrolizumab & Placebo

Total

Age, Continuous

ECOG 0

ECOG 1

Eastern Cooperative Oncology Group (ECOG performance) status scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.

ECOG 0=Fully active, able to carry on all pre-disease performance without restriction

ECOG=1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

ECOG Performance Status

Due to lack of grant funding, the other exploratory objectives to assess the changes in tumor and/or tissue texture on imaging, and to monitor and compare gut microbial communities in both arms, have not yet been able to be accomplished. The Investigators are looking for some way to fund the exploratory objectives in the future.

Derek Cridebring, PhD. Director, Molecular Medicine Division

All patients that receive trial treatment will be included in the analysis. Excludes 3 participants in the pembrolizumab + paricalcitol group: 1 participant that died due to other cause before 6 months, 2 participants who withdrew from study treatment before 6 months.

Progression- Free Survival at 6 Months From Initiation of Trial Treatment

Abdominal bloating

Abdominal pain

ALT increase

Alkaline phosphatase increase

Anemia

Arthralgia

AST increase

Creatinine increase

Hypertension

Hypophysitis

All patients who received any amount of trial treatment were included in the analysis. The reported AEs are those noted as possibly or definitely related to study agents.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genetically Engineered Cells (MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells) and Atezolizumab for the Treatment of Metastatic Triple Negative Breast Cancer, Urothelial Cancer, or Non-small Cell Lung Cancer	NCT04639245	Anatomic Stage ... Metastatic Lung... Metastatic Mali... Metastatic Trip... Metastatic Urot... Stage IV Lung C...	Atezolizumab Cyclophosphamid... Fludarabine MAGE-A1-specifi... PD1 Inhibitor	18 Years -	Fred Hutchinson Cancer Center
Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia	NCT04353479	Acute Myeloid L...	Camrelizumab(SH... Decitabine	60 Years - 75 Years	Shanghai Jiao Tong University School of Medicine
A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer	NCT03331562	Pancreatic Canc... Pancreas Adenoc... Advanced Pancre... Metastatic Panc... Metastatic Panc...	Pembrolizumab paricalcitol placebo	18 Years -	Translational Genomics Research Institute
A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer	NCT03331562	Pancreatic Canc... Pancreas Adenoc... Advanced Pancre... Metastatic Panc... Metastatic Panc...	Pembrolizumab paricalcitol placebo	18 Years -	Translational Genomics Research Institute
Genetically Engineered Cells (MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells) and Atezolizumab for the Treatment of Metastatic Triple Negative Breast Cancer, Urothelial Cancer, or Non-small Cell Lung Cancer	NCT04639245	Anatomic Stage ... Metastatic Lung... Metastatic Mali... Metastatic Trip... Metastatic Urot... Stage IV Lung C...	Atezolizumab Cyclophosphamid... Fludarabine MAGE-A1-specifi... PD1 Inhibitor	18 Years -	Fred Hutchinson Cancer Center
Downstaging Protocol Containing Immunotherapy for HCC Beyond the Milan Criteria Before Liver Transplantation	NCT05475613	Liver Transplan... Hepatocellular ...	Downstaging pro... Liver transplan...	18 Years - 75 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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