Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Irinotecan

Paclitaxel

Gemcitabine

Pembrolizumab

Leucovorin

Fluorouracil

Albumin-Bound Paclitaxel

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

400 mg per week as continous infusion until progression or intolerable toxicity

Olaptesed pegol

200 mg every 3 weeks as i.v. infusion until progression or intolerable toxicity or a maximum of 35 administrations

Diana Beyer, Dr.

The purpose of this study is to provide a go/no-go decision for a randomized expansion study by assessing the disease control rate (DCR) at 6 weeks for the combination of olaptesed pegol on top of pembrolizumab and (Arm 1) nanoliposomal irinotecan, 5-FU and leucovorin or (Arm 2) gemcitabine and nab-paclitaxel, to assess safety and tolerability and time-to-event endpoints.

Olaptesed With Pembrolizumab and Nanoliposomal Irinotecan or Gemcitabine/Nab-Paclitaxel in MSS Pancreatic Cancer

An Open-label Phase 2 Study of Olaptesed Pegol (NOX-A12) Combined With Pembrolizumab and Nanoliposomal Irinotecan/5-FU/Leucovorin or Gemcitabine/Nab-paclitaxel in Microsatellite-stable Metastatic Pancreatic Cancer Patients

Assessment of the disease control rate (DCR) at 6 weeks for the combination of olaptesed pegol on top of pembrolizumab and (Arm 1) nanoliposomal irinotecan, 5-FU and leucovorin or (Arm 2) gemcitabine and nab-paclitaxel

Safety and tolerability of olaptesed pegol pegol on top of pembrolizumab and (Arm 1) nanoliposomal irinotecan, 5-FU and leucovorin or (Arm 2) gemcitabine and nab-paclitaxel

Merck Sharp & Dohme LLC

TME Pharma AG

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Immunomodulating Agents

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)

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

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaptesed With Pembrolizumab and Nanoliposomal Irinotecan or Gemcitabine/Nab-Paclitaxel in MSS Pancreatic Cancer	NCT04901741	Metastatic Panc...	Olaptesed pegol 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
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

Spots Global Cancer Trial Database for olaptesed pegol