Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Breast Neoplasms

Stomach Neoplasms

Urinary Bladder Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Stomach Cancer

PRS-343

A multi center, open-label, Phase 1 dose escalation study with expansion cohort is designed to determine the MTD, RP2D and dosing schedule of PRS-343 in patients with HER2+ advanced or metastatic solid tumors.

The study will evaluate PRS-343 administered by intravenous (IV) infusion every 3 weeks (Schedule 1) initially. If safety, PK, and PD data suggest a different dosing schedule should be evaluated, Schedule 2 and/or 3 (dosing every 2 weeks in a 28-day cycle or once a week in a 21-day cycle, respectively) may be conducted. Separate MTDs may be determined for each schedule evaluated. Dose-limiting toxicities (DLTs) will be reported during the first cycle of each schedule (e.g., 21 days after the first dose in Cycle 1 for Schedule 1). Patients will be monitored for safety throughout the study. Dosing will continue until criteria for study drug discontinuation are met (disease progression or withdrawal from the study).

Patients with unknown HER2 status will be consented separately in a pre-screening visit in order to undergo HER2 testing prior to screening. All patients will be evaluated at screening (Day 28 to 1) and baseline (Day 1 predose).

Once the MTD has been established, up to 30 additional patients with locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2 targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder) may be enrolled in individual expansion cohorts. The expansion cohort will be enrolled at the MTD and/or at a lower dose level if safety/PD/PK/efficacy data support further evaluation of a lower dose level in order to determine the RP2D. The RP2D may be equivalent to or lower than the MTD.

An End-of-Treatment Visit will be performed at the time of treatment discontinuation. Patients will be evaluated 30 days after the End-of-Treatment Visit or prior to starting subsequent therapy, if sooner, at the Safety Follow-up Visit to assess any ongoing AEs as outlined in the protocol.

Obinutuzumab pre-treatment cohorts: The potential of obinutuzumab pre-treatment to reduce formation of ADA will be studied in a cohort of up to ten patients receiving PRS-343 at a dose of 8 mg/kg Q2 weeks (corresponding to Cohort 11b).

Patients will be assessed for tumor response/progression per RECIST v1.1

PRS-343 in HER2-Positive Solid Tumors

A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors

Pieris Pharmaceuticals, Inc.

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Antibodies

Immunomodulating Agents

Antibodies, Bispecific

Immunoglobulins

The initial cohorts will enroll sequentially as single participant cohorts. If no DLT or ≥Grade 2 study drug related adverse event is observed, then dosing will proceed in a 3+3 design. Additional participants will be recruited into the PK/PD expansion cohorts at dose levels deemed safe during dose escalation. Once a tolerated dose has been established participants will be recruited into tumour-specific expansion cohorts.

Dosing of participants will occur intravenously (IV), at a fixed dose in treatment cycles once every 4 weeks (Q4W) until disease progression or unacceptable toxicity.

FS222

invoX Clinical Trials

Marina Maglakelidze, MD

Laurentia Nicoleta Gales, MD

Alexandru Grigorescu, MD

Tudor Ciuleanu, MD

Ignacio Melero Bermejo, Ldo.

Guzman Alonso Casal, MD

Elena Garralda Cabanas, Ldo.

Javier Garcia Corbacho, Ldo.

Marc Cucurull Salamero

Delvys Rodriguez-Abreu, MD

Victor Moreno, MD

Gillermo de Velasco Oria de Rueda, Ldo.

Valentina Boni, MD

Mariano Provencio Pulla, MD

Teresa Garcia Manrique, MD

Andrés Cervantes Ruiperez, Ldo.

This study will be conducted in adult participants diagnosed with advanced tumours to characterize the safety, tolerability, pharmacokinetics (PK), and activity of FS222. This is a Phase 1, multi-center, open label, multiple-dose, first in human study, designed to systematically assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for FS222 in participants with advanced tumours. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

FS222 First in Human Study in Patients With Advanced Malignancies

A Phase 1, Open-Label, First-in-Human Study to Evaluate the Safety and Anti-tumour Activity of FS222, a CD137/PD-L1 Bispecific Antibody, in Subjects With Advanced Malignancies

Safety and tolerability will be evaluated by collection of AEs and SAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

Toxicity will be evaluated according to the NCI CTCAE Version 5.0.

invoX Pharma Limited

Antineoplastic Agents

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

PRS-343 in Combination with Atezolizumab

A Phase 1b, open-label, dose escalation study of PRS-343 in combination with atezolizumab in patients with HER2-positive advanced or metastatic solid tumors.

This is a multicenter, open-label Phase 1b study to determine the MTD and RP2D and to assess the safety and efficacy of PRS-343 administered in combination with atezolizumab, a PD-L1 antibody, in previously treated advanced or metastatic HER-2 positive solid tumors (e.g., bladder, breast and gastrointestinal). The study will include a dose escalation period followed by an expansion period. PRS-343 and atezolizumab will be given intravenously once every three weeks (Q3W).

All available safety data, emerging PK, pharmacodynamic data, and dose limiting toxicities (DLTs) will be considered in guiding the Safety Committee's decisions regarding subsequent doses to be tested during the escalation phase of the study. Once the MTD and RP2D have been established, an expansion cohort will be enrolled.

One treatment cycle is defined as 21 days (3 weeks).

Single Group Assignment Drug PRS-343 Combination Therapy

PRS-343 in Combination With Atezolizumab in HER2-Positive Solid Tumors

A Phase 1b, Open-Label, Dose Escalation Study of PRS-343 in Combination With Atezolizumab in Patients With HER2-Positive Advanced or Metastatic Solid Tumors

Blood and Lymph Conditions

Immune System Diseases

Behaviors and Mental Disorders

Recurrence

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

Aggression

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

B-cell Lymphoma

Acute Graft Versus Host Disease

Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

Three dose levels will be evaluated.

Group 1: CD19.CAR/28137ζ at 1×10\^6 cells/m\^2 and CD19.CAR/28ζ at 1×10\^6 cells/m\^2

Group 2: CD19.CAR/28137ζ at 5×10\^6 cells/m\^2 and CD19.CAR/28ζ at 5×10\^6 cells/m\^2

Group 3: CD19.CAR/28137ζ at 2×10\^7 cells/m\^2 and CD19.CAR/28ζ at 2×10\^7 cells/m\^2

Dose Escalation Phase:CD19.CAR/28 and CD19.CAR/28137 T cells

The primary goal of the expanded cohort is to further study the safety profiles of CAR-T cells in each of the disease settings, both with or without lymphodepleting chemotherapy given before CAR-T cell infusion.

Expansion Phase: CD19.CAR/28 and CD19.CAR/28137 T cells

Carlos A Ramos, MD

Mahshid Azamian

Carlos A. Ramos, MD

Subjects on this study have a type of lymph gland cancer called Non-Hodgkin Lymphoma, acute lymphocytic leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment.

The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients.

T cells can kill tumor cells but normally there are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person.

The antibody used in this study is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, anti-CD19 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor.

In the laboratory, the investigators found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer in the body but not long enough for them to be able to kill the lymphoma cells. The investigators believe that if they add an extra stimulating protein, called CD137, the cells will have a better chance of killing the lymphoma cells.

The investigators are going to see if this is true by putting the CD19 chimeric receptor with CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA.

The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how long the T cell with each sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.

Patients will give the investigators blood to make CD19 CD28 (with and without CD137) chimeric receptor-T cells in the laboratory. These cells will be grown and frozen. To make the T cells, investigators will take blood (or blood from a donor) and stimulate it with growth factors to make the T cells grow. To get the CD19 antibody and CD28 (with or without CD137) to attach to the surface of the T cell, they will insert the antibody gene into the T cell. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps to find the T cells in the blood after injecting them; in order to tell them apart investigators have made two viruses that are slightly different because one has CD137. These two viruses can be told apart by a special laboratory test. Because the patient will receive cells with a new gene in them, the patient will be followed for a total of 15 years to see if there are any long term side effects of gene transfer. If the patient cannot visit the clinic, he or she will be contacted by the research coordinator or physician.

When subjects enroll on this study, they will be assigned a dose of CD19 chimeric receptor-T cells. Several studies suggest that the infused T cells need room to be able to proliferate and accomplish their functions and that this may not happen if there are too many other T cells in circulation.

Because of that, if the subject's level of circulating T cells is relatively high, s/he may receive one treatment of cyclophosphamide (Cytoxan) and fludarabine if the doctor thinks this is appropriate. This drug will decrease the numbers of the subject's own T cells before infusion of the CD19 chimeric receptor T cells. If subject is already receiving chemotherapy, this may not be needed. The investigators would prefer subjects do not receive other chemotherapy until 6 weeks after cell infusion but they can do so if their doctor thinks it is medically necessary.

Patients will be given an injection of cells into the vein through an IV at the assigned dose. The injection will take about 20 minutes. The investigators will follow them in the clinic after the injection for up to 3 hours.

If after a 6 week evaluation period after the infusion, the patient seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), s/he may be able to receive up to five additional doses of the T cells if s/he wishes. The first repeat infusion can only take place at least 6 weeks after the first infusion. Any additional infusions after that would be at least 4 weeks apart. All additional infusions will be at the same dose level received the first time or a lower dose. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)

Phase I Study of Activated T-Cells Expressing Second or Third Generation CD19-Specific Chimeric Antigen Receptors for Advanced B-Cell Non-Hodgkin's Lymphoma, Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia (SAGAN)

Toxicity will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 4. DLT will be defined as any of the following that is NOT (1) pre-existing, or (2) due to infection (to which patients with CLL and NHL are predisposed), or (3) due to underlying malignancy, and that may, after consultation with the FDA when indicated, be considered possibly, probably, or definitely related to the study cellular products: (1) Non-hematologic DLT is any grade 3 or grade 4 non-hematologic toxicity, including allergic reactions to T cell infusions; (2) Hematologic DLT is defined as any grade 4 hematologic toxicity. Patients with evidence of bone marrow disease (metastases or diffuse infiltration) are not evaluable for hematologic dose limiting toxicity.

Survival will be measured by a real time Q-PCR assay to detect CD19.CAR-ATLs in peripheral blood from subjects. Plots will be generated to depict patterns of survival. Also, longitudinal modeling techniques will be used.

To compare the changes in frequency of two different T-cell products in the same patient, two different Q-PCR assays will be used, which distinguish each CAR by the presence or absence of the CD137 co-stimulatory endodomain gene.

Tumor responses will be assessed by the International Working Group Revised Response Criteria for Malignant Lymphoma or the National Cancer Institute CLL Working Group Recommendations, as applicable.

Changes in the percentage of circulating modified T cells after additional doses will be measured by each respective real time Q-PCR assay to detect CD19.CAR-ATLs in peripheral blood from subjects. Plots will be generated to depict patterns of survival. Also, longitudinal modeling techniques will be used.

To study the function of CD19.CAR-ATLs, the following assays will be performed on PBMCs isolated from subjects: (1) ELISPOT for interferon-gamma release using CD19-positive cells and CD19-negative target cells; (2) Other functional assays, such as in vitro reactivation of PBMCs, in patients on whom the appropriate reagents are available; and (3) Immunophenotyping.

Center for Cell and Gene Therapy, Baylor College of Medicine

The Methodist Hospital Research Institute

Baylor College of Medicine

Professor

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Tucatinib

Ramucirumab

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients aged 18 years or older with HER2-positive gastric or GEJ adenocarcinoma who have progressed on prior treatment with a regimen containing a platinum and fluoropyrimidine and a HER2-directed therapy such as trastuzumab and now are candidates for treatment with ramucirumab and paclitaxel

Patients aged 18 years or older with HER2 low (IHC 1+ or IHC 2+ without HER2/neu amplification) gastric or GEJ adenocarcinoma who have received at least one prior treatment regimen

Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel

Cinrebafusp alfa (PRS-343) in combination with tucatinib

Gordon Otto, MD, PhD

A Phase 2, multi-center, open-label study of cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel in patients with HER2-high and in combination with tucatanib in patients with HER2-low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This is a multi-center, open-label study of cinrebafusp alfa in combination with clinically established doses of ramucirumab and paclitaxel in patients with HER2-positive (IHC 3+ or IHC 2+ with HER2/neu gene amplification) gastric or GEJ adenocarcinoma (Arm 1) and in combination with tucatinib in patients with low levels of HER2 (IHC 1+ or IHC 2+ without HER2/neu amplification) (Arm 2).

Parallel Group Assignment Drug Cinrebafusp Alfa (PRS-343) Combination Therapy

Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma

A Phase 2, Multi-Center, Open-Label Study of Cinrebafusp Alfa (PRS-343) in Combination With Ramucirumab and Paclitaxel in Patients With HER2-Positive Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and in Combination With Tucatinib in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PRS-343 in HER2-Positive Solid Tumors	NCT03330561	HER2-positive B... HER2-positive G... HER2-positive B... HER2-positive S...	PRS-343	18 Years -	Pieris Pharmaceuticals, Inc.
FS222 First in Human Study in Patients With Advanced Malignancies	NCT04740424	Advanced Cancer Metastatic Canc...	FS222	18 Years -	invoX Pharma Limited
PRS-343 in Combination With Atezolizumab in HER2-Positive Solid Tumors	NCT03650348	HER2-positive B... HER2-positive G... HER2-positive B... HER2-positive S...	PRS-343 in Comb...	18 Years -	Pieris Pharmaceuticals, Inc.
Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)	NCT01853631	Non-Hodgkin Lym... Chronic Lymphoc... Acute Lymphocyt...	Dose Escalation... Expansion Phase...	- 75 Years	Baylor College of Medicine
PRS-343 in HER2-Positive Solid Tumors	NCT03330561	HER2-positive B... HER2-positive G... HER2-positive B... HER2-positive S...	PRS-343	18 Years -	Pieris Pharmaceuticals, Inc.
Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma	NCT05190445	HER2-positive G...	Cinrebafusp alf... Cinrebafusp alf...	18 Years -	Pieris Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for cd137

Every month we try and update this database with for cd137 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cd137

Every month we try and update this database with for cd137 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cd137 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.