Metastatic Colorectal CancerPhase 1/2Keynote-559NCT03168139
Olaptesed (NOX-A12) Alone and in Combination With Pembrolizumab in Colorectal and Pancreatic Cancer
A Phase 1/2 study testing Olaptesed pegol - Monotherapy and Olaptesed pegol + Pembrolizumab - Combination Therapy in people with Metastatic Colorectal Cancer and Metastatic Pancreatic Cancer, run by TME Pharma AG at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, Metastatic Pancreatic Cancer
- What is being tested?
- Olaptesed pegol - Monotherapy and Olaptesed pegol + Pembrolizumab - Combination Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 18 Apr 2017to 25 Mar 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- Platelets ≥ 100,000/mm³ (≥ 100 x 10^9/L)
- Creatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m²
- Total bilirubin ≤ 1.5 x ULN (upper limit normal)
- ALT (alanine transaminase) ≤ 5 x ULN
- AST (aspartate transaminase) ≤ 5 x ULN
- INR (International Normalized Ratio) or PT (Prothrombin Time) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- aPTT (Activated Partial Thromboplastin Time) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female patients of child-bearing potential must have a negative urine or serum pregnancy test within 28 days prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Patients must agree to use an effective method of contraception or be abstinent during and for 120 days following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)
- Male patients must use an effective barrier method of contraception during study and for 120 days following the last dose if sexually active with a FCBP
Who cannot join
- 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
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- 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
- History of interstitial lung disease
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- History of anaphylaxis or severe drug hypersensitivity reactions
- Active infection requiring systemic therapy
- Known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or with another confirmed or suspected immunosuppressive or immunodeficient condition
- Concurrent chronic severe medical problems (heart failure, uncontrolled diabetes, bleeding disorder etc.), unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator, is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
- Women of childbearing potential: refusal or inability to use effective means of contraception
- Contra-indication or known hypersensitivity to olaptesed pegol, polyethylene glycol, pembrolizumab or further ingredients to the investigational medicinal products
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- Previous enrolment in this clinical study
Trial locations and contacts
1 site in 1 country.
Germany1 site
Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Heidelberg, 69120
About this study
Official title: 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
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.
Read the detailed description
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.
- Being tested
- Olaptesed pegol - Monotherapy, Olaptesed pegol + Pembrolizumab - Combination Therapy
- 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
- Medical subject headings
- Colorectal Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olaptesed pegol - MonotherapyDrug
Also called NOX-A12
Monotherapy (MT) period:
Treatment with 300 mg olaptesed pegol only, weekly on MT D1 and MT D4 for up to 2 weeks
Olaptesed pegol + Pembrolizumab - Combination TherapyDrug
Also called NOX-A12, Keytruda, MK-3475
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
| Study group | Role | What they receive |
|---|---|---|
| Olaptesed pegol + Pembrolizumab | Experimental | Not described Receives: Drug: Olaptesed pegol - Monotherapy; Drug: Olaptesed pegol + Pembrolizumab - Combination Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monotherapy: Pharmacodynamics
Evaluation of changes within the tumor microenvironment induced by CXCL12 inhibition with olaptesed pegol by comparing pre- and post-treatment biopsy specimens
Measured: 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
Measured: up to 24 months
Secondary outcomes (4)
Monotherapy: Safety
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)
Measured: up to 14 days
Monotherapy: Pharmacodynamics
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
Measured: up to 14 days
Combination Therapy: Disease control rate (DCR)
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.
Measured: up to 24 months
Combination Therapy: Efficacy - time to event analyses
Efficacy of treatment with olaptesed pegol in combination with pembrolizumab (PFS and OS)
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start18 Apr 2017
- Primary completion25 Mar 2020
- Study completion25 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- TME Pharma AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03168139
- Sponsor's protocol ID
- SNOXA12C601
- Other IDs
- 2016-003657-15, Keynote-559, 2016
- Acronym
- Keynote-559
- Status last verified
- Jul 2020
- First submitted
- 19 May 2017
- Last updated
- 8 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03168139
- Acronym / sponsor ID
- Keynote-559 / SNOXA12C601
- Keywords
- Metastatic colorectal cancer, Metastatic pancreatic cancer, NOX-A12, Olaptesed pegol, Spiegelmer, Pembrolizumab, PD-1 inhibitor, Stromal cell-derived factor-1 (SDF-1)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- TME Pharma AGIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 25 Mar 2020 (actual)
- Study completion
- 25 Mar 2020 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaptesed pegol + Pembrolizumab | Experimental | Drug: Olaptesed pegol - Monotherapy, Drug: Olaptesed pegol + Pembrolizumab - Combination Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaptesed pegol - MonotherapyAlso: NOX-A12Monotherapy (MT) period: Treatment with 300 mg olaptesed pegol only, weekly on MT D1 and MT D4 for up to 2 weeks | Drug | Olaptesed pegol + Pembrolizumab |
| Olaptesed pegol + Pembrolizumab - Combination TherapyAlso: NOX-A12, Keytruda, MK-3475Combination 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 | Drug | Olaptesed pegol + Pembrolizumab |
Primary outcome
Monotherapy: Pharmacodynamics
Time frame: up to 14 days
Evaluation of changes within the tumor microenvironment induced by CXCL12 inhibition with olaptesed pegol by comparing pre- and post-treatment biopsy specimens
Combination Therapy: Safety - adverse events, vital signs, ECG, hematology & safety laboratory
Time frame: up to 24 months
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
4 secondary outcomes
Monotherapy: Safety
Time frame: up to 14 days
Monotherapy: Pharmacodynamics
Time frame: up to 14 days
Combination Therapy: Disease control rate (DCR)
Time frame: up to 24 months
Combination Therapy: Efficacy - time to event analyses
Time frame: up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Olaptesed pegol - Monotherapy and Olaptesed pegol + Pembrolizumab - Combination Therapy in people with Metastatic Colorectal Cancer and Metastatic Pancreatic Cancer, run by TME Pharma AG at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monotherapy: Pharmacodynamics (time frame: up to 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2020.