Clinical Trials

Date: 2017-09-28

Type of information: update on patient enrollment

phase: 1-2

Announcement: update on patient enrollment

Company: Noxxon Pharma (Germany) Merck&Co (USA - NJ)

Product: pembrolizumab and olaptesed pegol (NOX-A12)

Action mechanism:

  • monoclonal antibody/immune checkpoint inhibitor/spiegelmer. Keytruda® (pembrolizumab - MK-3475) is a highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. Keytruda® is the first approved drug that blocks the PD-1 cellular pathway.
  • Olaptesed pegol/NOX-A12 specifically antagonizes CXCL12/SDF-1 (CXC Chemokine Ligand 12 / Stromal Cell-Derived Factor-1), a chemokine which attracts and activates immune and non-immune cells including stem cells from the bone marrow. CXCL12 binds with high affinity to two chemokine receptors, CXCR4 and CXCR7. The CXCL12 / CXCR4 / CXCR7 axis has been shown to play a role in stem cell mobilization, vasculogenesis, tumor growth and metastasis. CXCL12 signaling has been shown to play an important role in the pathophysiology of CLL, especially in the interaction of leukemic cells with the tissue microenvironment. The therapeutic concept of NOX-A12 is to inhibit such tumor-supporting interactions and thereby sensitize CLL cells to chemotherapy.

Disease: metastatic colorectal cancer, metastatic pancreatic cancer

Therapeutic area: Cancer - Oncology

Country: Germany

Trial details:

  • 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.
  • Noxxon and Merck&Co collaborated closely in the two-arm clinical trial design that is composed of two parts: patients will receive NOX-A12 monotherapy for two weeks, followed by combination therapy of NOX-A12 plus Keytruda® for up to two years.
  • The primary purpose of part 1 of the trial is to confirm that treatment with NOX-A12 can modulate the tumor microenvironment including the type, number and/or distribution of immune cells, such as cytotoxic T cells as well as chemokine and cytokine signatures in the tumor tissue. All patients completing part 1 move to part 2, in which they receive NOX-A12 in combination with Keytruda®. Part 2 is designed to explore the safety, tolerability and efficacy of NOX-A12 in combination with Keytruda®.
  • This open-label trial is designed to include 20 patients, 10 patients for each metastatic pancreas and colorectal cancer. (NCT03168139)

Latest news:

  • • On September 28, 2017, Noxxon Pharma provided an update on the ongoing Phase 1/2 combination trial with NOX-A12 and Keytruda® (pembrolizumab) in pancreatic and colorectal cancer patients. The trial has enrolled 10 patients and therefore has successfully reached the halfway mark of the overall enrollment. The trial remains on schedule to deliver top-line biopsy analysis following NOX-A12 monotherapy and top-line response rates for all 20 patients to NOX-A12 in combination with Keytruda® in the second and fourth quarters of 2018 respectively. Based on initial review of the two-week NOX-A12 monotherapy portion of the open-label study, NOX-A12’s safety and tolerability continue to be in line with previously reported and published data in that patients exhibit no major drug-related adverse effects. In addition, the currently available data from the first four enrolled patients suggest that NOX-A12 is able to penetrate into tumor tissue where it binds and neutralizes its target in both colorectal and pancreatic cancer patients. This analysis is based on levels of CXCL12 (C-X-C Chemokine Ligand 12), NOX-A12’s target, and other biomarkers measured in tumor biopsies.
  • • On  July 4, 2017, Noxxon Pharma announced that the first patients were treated in its Phase 1/2 clinical trial in patients with metastatic colorectal and pancreatic cancer at the National Center for Tumor Diseases in Heidelberg, Germany. The goal of the trial is to evaluate safety and the effects of NOX-A12 (olaptesed pegol) as a monotherapy on immune cell infiltration into tumors in addition to safety and efficacy of NOX-A12 in combination with Keytruda® (pembrolizumab), a programmed death receptor-1 (PD-1) immune checkpoint-inhibiting antibody marketed by Merck&Co.
  • Two patients have now completed part 1 of the trial in which they received NOX-A12 monotherapy for two weeks. Data from this stage will be used to analyze safety and, through tumor biopsies taken before and after NOX-A12 treatment, the ability of NOX-A12 to modulate the tumor microenvironment including the number of T-cells present in the tumors.
  • Part 1 could, as such, provide clinical data to support the broad potential applicability for combinations of NOX-A12 not only with checkpoint inhibitors but also other T-cell based therapeutics such as CAR-T approaches. Both patients that completed part 1 have now progressed into part 2, receiving NOX-A-12 in combination with Keytruda®. Top-line data for all 20 patients from part 1 is targeted to be available in Q2 2018, and initial response-rate data in Q4 2018.

Is general: Yes