Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Monotherapy (MT) period:

Treatment with 300 mg olaptesed pegol only, weekly on MT D1 and MT D4 for up to 2 weeks

Olaptesed pegol - Monotherapy

Combination therapy (CT) period:

Treatment with 300 mg olaptesed pegol in combination with 200 mg pembrolizumab every three weeks (Q3W) until progressive disease or limiting toxicity, for a maximum of 24 months in total

Olaptesed pegol + Pembrolizumab - Combination Therapy

The purpose of this study is to show that the type, number and/or distribution of tumor metastases infiltrating immune cells such as cytotoxic T cells and/or the cytokine signature in the tumor metastases can be modulated by treatment with olaptesed pegol and to explore safety, tolerability and efficacy of olaptesed pegol in combination with pembrolizumab as a basis for subsequent studies in combination with immunotherapies, in particular checkpoint inhibitors.

Olaptesed pegol (NOX-A12) targets a key chemokine in the tumor microenvironment, CXCL12, which is naturally involved in the homeostasis of blood and immune cells. In cancer, CXCL12 acts as a communication bridge between tumor cells and their environment. In particular, it confers resistance to checkpoint inhibitors through T-cell exclusion in preclinical models. The hypothesis is that inactivation of CXCL12 by olaptesed pegol induces changes in the tumor microenvironment of patients with colorectal and pancreatic cancer which render the tumors more susceptible to immuno-oncological approaches such as checkpoint inhibition.

Olaptesed (NOX-A12) Alone and in Combination With Pembrolizumab in Colorectal and Pancreatic Cancer

A Two-part, Open-label Phase 1/2 Study to Evaluate Pharmacodynamic Effects and Safety of Olaptesed Pegol Monotherapy and Safety and Efficacy of Olaptesed Pegol / Pembrolizumab Combination Therapy in Metastatic Colorectal and Pancreatic Cancer

Evaluation of changes within the tumor microenvironment induced by CXCL12 inhibition with olaptesed pegol by comparing pre- and post-treatment biopsy specimens

Safety and tolerability of olaptesed pegol in combination with pembrolizumab will be evaluated by assessing adverse events, vital signs (pulse rate, blood pressure), 12-lead ECG, hematology (full blood count including platelets and differential count), safety laboratory including thyroid function tests

Assessment of safety and tolerability of olaptesed pegol in patients with metastatic (stage IV) colorectal and pancreatic cancer (adverse events, vital signs (pulse rate, blood pressure), 12-lead ECG, hematology (full blood count including platelets and differential count), safety laboratory)

Investigation of changes in the cytokine/chemokine signature within the tumor microenvironment and in the peripheral blood induced by CXCL12 inhibition with olaptesed pegol by comparing the pre- and post-treatment samples

DCR will be calculated as the proportion of patients with best overall response to treatment with olaptesed pegol in combination with pembrolizumab of complete response (CR), partial response (PR) or stable disease (SD).

Treatment responses will be assessed according to the current guidelines of the RECIST 1.1 and irRECIST.

Efficacy of treatment with olaptesed pegol in combination with pembrolizumab (PFS and OS)

Merck Sharp & Dohme LLC

TME Pharma AG

Nervous System Diseases

Glioblastoma

Brain Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Bevacizumab

Angiogenesis Inhibitors

Growth Inhibitors

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, bevacizumab every two weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely or not resected patients

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients

Olaptesed pegol continuous administration for 26 weeks

Olaptesed pegol

Radiotherapy in weeks 1-6; cumulative dose of 60 Gy in 2 Gy fractions

Radiotherapy

Bevacizumab every 2 weeks i.v. for 26 weeks

Pembrolizumab every 3 weeks i.v. for 26 weeks

The purpose of this study is to obtain first, exploratory information on the safety and efficacy of (i) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete tumor resection, (ii) olaptesed pegol in combination with radiation therapy and bevacizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete or complete tumor resection, (iii) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after complete tumor resection, and (iv) olaptesed pegol in combination with radiation therapy and pembrolizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after either complete or incomplete tumor resection.

3+3 dose escalation and a 3-arm expansion group

Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients

Single-arm Dose-escalation Phase 1/2 Study of Olaptesed Pegol (NOX-A12) in Combination With Irradiation in Inoperable or Partially Resected First-line Glioblastoma Patients With Unmethylated MGMT Promoter With a 3-arm Expansion Group Including Fully Resected Patients and Combination With Bevacizumab or Pembrolizumab

Number of patients with treatment-related adverse events as assessed by CTCAE

Progression free survival at 6 months (PFS-6) in %

Median progression-free survival (mPFS) in months

Changes from baseline in tumor vascularization over time as %cerebral blood volume

concentration of olaptesed pegol in plasma in µmol/L

Quality of Life measures are recorded according to EORTC QLQ30 module, which is validated for cancer patients in general and measured as a unit of scale. This is a standard tool for assessing patient reported quality of Life along time during treatment.

Quality of Life measures are recorded according to EORTC QLQ BN-20 module, which is validated for brain tumor patients and measured as a unit of scale. This is a standard tool for assessing patient reported quality of Life along time during treatment.

Change from baseline in neurologic performance scores by Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The NANO Scale evaluates 9 major domains of neurologic function, with each domain being scored on a range from 0 to 2 or 3.

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Pilot Group (NOX-A12 single agent, and combined with BR):

* 3 cohorts of 3 patients will receive treatment with NOX-A12 alone at a single dose of 1, 2 or 4 mg/kg i.v. 2 weeks before the combination treatment of NOX-A12 and BR begins.The combination of NOX-A12 and BR will follow a dose titration design beginning at 1 mg/kg NOX-A12 (cycle 1), proceeding to dose levels of 2 mg/kg (cycle 2) and 4 mg/kg (cycle 3) NOX-A12 in combination with BR. This is followed by consolidation in cycles 4-6 when NOX-A12 will be kept at the highest individually titrated dose.

Expansion Group (NOX-A12 in combination with BR):

* Expansion patients will not receive single agent NOX-A12, but will receive combination treatment as for the pilot group.

NOX-A12

Kai Riecke, MD

The purpose of this study is to evaluate the safety and efficacy of NOX A12 in combination with a background therapy of bendamustine and rituximab (BR) chemotherapy in previously treated patients with chronic lymphocytic leukemia (CLL).

CLL cells express high levels of CXCR4 chemokine receptors, which cause leukemia cell migration and adhesion to stromal cells secreting the CXCR4 ligand, CXCL12 (or stromal-derived-factor 1, SDF-1). NOX A12 is a specific CXCL12 antagonist and may improve BR therapy by disrupting CXCR4-CXCL12 interactions, thereby mobilizing CLL cells from protective tissue microenvironments to the blood. Furthermore, SDF-1 inhibition may alter the activation status of CLL cells, thereby triggering apoptosis or sensitization of CLL cells towards chemotherapy.

NOX-A12 in Combination With Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL)

A Multi-center, Open Label, Uncontrolled, Phase IIA Clinical Trial Evaluating the Safety and Efficacy of NOX A12 in Combination With a Background Therapy of Bendamustine and Rituximab (BR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

The safety evaluation will be based on the following assessments:

* adverse events
* vital signs
* 12 lead ECGs
* laboratory parameters
* immunogenicity

Assessment of the complete remission rate after cycle 3 and 6 will be the primary efficacy endpoint. The 1996 NCI-WG criteria which have been updated in 2008 will be applied.

The pharmacodynamics evaluation will be based on the following assessments:

* mobilization of peripheral blood CD34+ cells and CLL cells
* plasma concentration of SDF-1/CXCL12

The pharmacokinetics evaluation will be based on the following assessments:

* plasma concentration of NOX-A12
* 24-hour urine excretion of NOX-A12

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaptesed (NOX-A12) Alone and in Combination With Pembrolizumab in Colorectal and Pancreatic Cancer	NCT03168139	Metastatic Colo... Metastatic Panc...	Olaptesed pegol... Olaptesed pegol...	18 Years -	TME Pharma AG
Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients	NCT04121455	Glioblastoma	Olaptesed pegol Radiotherapy Bevacizumab Pembrolizumab	18 Years -	TME Pharma AG
Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients	NCT04121455	Glioblastoma	Olaptesed pegol Radiotherapy Bevacizumab Pembrolizumab	18 Years -	TME Pharma AG
Olaptesed (NOX-A12) Alone and in Combination With Pembrolizumab in Colorectal and Pancreatic Cancer	NCT03168139	Metastatic Colo... Metastatic Panc...	Olaptesed pegol... Olaptesed pegol...	18 Years -	TME Pharma AG
NOX-A12 in Combination With Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL)	NCT01486797	Chronic Lymphoc...	NOX-A12	18 Years -	TME Pharma AG

Spots Global Cancer Trial Database for spiegelmer

Every month we try and update this database with for spiegelmer 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 spiegelmer

Every month we try and update this database with for spiegelmer 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 spiegelmer 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.