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

NCT03168139 | Completed Phase 1

• 3 other identifiers: SNOXA12C6012016-003657-15Keynote-559
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer; Metastatic Pancreatic Cancer

Keywords

Metastatic colorectal cancer; Metastatic pancreatic cancer; NOX-A12; Olaptesed pegol; Spiegelmer; Pembrolizumab; PD-1 inhibitor; Stromal cell-derived factor-1 (SDF-1); CXCL12; Tumor microenvironment; Immunotherapy; Checkpoint inhibition

Outcome Measures

Primary Outcomes (2)

• Monotherapy: Pharmacodynamics

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

  up to 14 days

• Combination Therapy: Safety - adverse events, vital signs, ECG, hematology & safety laboratory

  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

  up to 24 months

Secondary Outcomes (4)

• Monotherapy: Safety

  up to 14 days

• Monotherapy: Pharmacodynamics

  up to 14 days

• Combination Therapy: Disease control rate (DCR)

  up to 24 months

• Combination Therapy: Efficacy - time to event analyses

  up to 24 months

Study Arms (1)

Olaptesed pegol + Pembrolizumab

EXPERIMENTAL

Drug: Olaptesed pegol - Monotherapy; Drug: Olaptesed pegol + Pembrolizumab - Combination Therapy

Interventions

Olaptesed pegol - Monotherapy DRUG

Monotherapy (MT) period: Treatment with 300 mg olaptesed pegol only, weekly on MT D1 and MT D4 for up to 2 weeks

Also known as: NOX-A12

Olaptesed pegol + Pembrolizumab

Olaptesed pegol + Pembrolizumab - Combination Therapy DRUG

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

Also known as: NOX-A12, Keytruda, MK-3475

Olaptesed pegol + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age ≥18 years
• a) Male or female patient with a history of treated metastatic stage IV colorectal cancer with liver metastases of the primary colorectal cancer after two or more lines of prior treatment OR b) Male or female patient with a history of treated metastatic stage IV pancreatic ductal adenocarcinoma with liver metastases of the primary pancreatic cancer after one or more lines of prior treatment
• Histologically or cytologically confirmed diagnosis of colorectal or pancreatic ductal cancer with liver metastasis
• Measurable disease based on RECIST 1.1 as determined by the site study team
• Expected survival of at least three months
• Patient with liver metastasi(e)s amenable to repeated biopsies
• Patient agreeing to repeated biopsies of metastases
• Karnofsky performance status ≥80 %
• a) Colorectal cancer patients that have received current standard treatment options (progression or intolerance to oxaliplatin, irinotecan, 5-fluorouracil and trifluridine/tipiracil with or without treatment combinations of cetuximab and/or bevacizumab, or ramucirumab or panitumumab, or regorafenib, including monotherapies with any of these options) OR b) Pancreatic cancer patients that have received current treatment options (progression or intolerance to combination therapies with oxaliplatinum, irinotecan, 5-fluorouracil, gemcitabine, nab-paclitaxel or erlotinib, including monotherapies with any of these options)
• No chemotherapy treatment within the last three weeks prior to study MT Day 1
• Resolution of toxic effect(s) of the most recent prior chemotherapy to levels deemed appropriate by the investigator; if patients have received major surgery, they must have recovered from the toxicity and/or complications from the intervention
• The following laboratory parameters should be within the ranges specified:
• Hemoglobin (Hb) ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000/mm³ (≥ 1.0 x 10\^9/L)

You may not qualify if:

• Inability to personally provide written informed consent or to understand and collaborate throughout the study
• Inability or unwillingness to comply with study requirements
• Patients with metastatic lesions suitable for resection
• Patients with metastatic cancer that have a drastic clinical progression (e.g. from Karnofsky performance 100% to 70%) within the last six weeks before screening
• Participation in any clinical research study with administration of an investigational drug or therapy within 30 days prior to enrolment in the study
• Use of any investigational or non-registered product (drug or vaccine) other than the study treatment
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in pembrolizumab clinical studies
• Prior radiation therapy of tumor/metastases
• Diagnosis of immunodeficiency or requiring concomitant chronic treatment with systemic corticosteroids or any other immunosuppressive agents within 7 days prior to the first dose of study treatment; the use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor
• Intake of immunomodulatory medication (Type 1 interferons)
• Prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to study MT Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to such agents administered more than 2 weeks earlier
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study MT Day 1 or no recovery (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
• Prior transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study MT Day 1
• Live vaccine within 30 days prior to the first dose of study treatment
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

Sponsors & Collaborators

• TME Pharma AG: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

Heidelberg, 69120, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms

Interventions

NOX-A12; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: May 30, 2017
• Study Start: April 18, 2017
• Primary Completion: March 25, 2020
• Study Completion: March 25, 2020
• Last Updated: July 8, 2020

Record last verified: 2020-07

Locations

DE (1)