| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Colorectal cancer with liver metastases
Pancreatic cancer with liver metastases
|
Kolorektalkrebs mit Lebermetastasen
Pankreaskrebs mit Lebermetastasen |
|
| E.1.1.1 | Medical condition in easily understood language |
Colorectal cancer with liver metastases
Pancreatic cancer with liver metastases |
Kolorektalkrebs mit Lebermetastasen
Pankreaskrebs mit Lebermetastasen |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10052358 |
| E.1.2 | Term | Colorectal cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033605 |
| E.1.2 | Term | Pancreatic cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Monotherapy part:
Pharmacodynamics – evaluation of immune infiltrate changes within the tumor microenvironment induced by CXCL12 inhibition with olaptesed pegol by comparing pre- and post-treatment biopsy specimens
Combination therapy part:
To assess safety and tolerability of olaptesed pegol in combination with pembrolizumab
|
|
| E.2.2 | Secondary objectives of the trial |
Monotherapy part:
Safety – assessment of safety and tolerability of olaptesed pegol in patients with metastatic (stage IV) colorectal and pancreatic cancer
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
Combination therapy part:
To explore the efficacy of treatment with olaptesed pegol in combination with pembrolizumab
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent
2. Age ≥18 years
3. 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
4. Histologically or cytologically confirmed diagnosis of colorectal or pancreatic ductal cancer
with liver metastasis
5. Measurable disease based on RECIST 1.1 as determined by the site study team
6. Expected survival of at least three months
7. Patient with liver metastasi(e)s amenable to repeated biopsies
8. Patient agreeing to repeated biopsies of metastases
9. Karnofsky performance status ≥80 %
10. a) Colorectal cancer patients that have received current standard treatment options (progression or intolerance to oxaliplatin, irinotecan, 5-fluorouracil and/or 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)
11. No chemotherapy treatment within the last three weeks prior to study MT Day 1
12. 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
13. 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 109/L)
Platelets ≥ 100,000/mm3 (≥ 100 x 109/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
14. 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)
15.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
|
|
| E.4 | Principal exclusion criteria |
1. Inability to personally provide written informed consent or to understand and collaborate throughout the study
2. Inability or unwillingness to comply with study requirements
3. Patients with metastatic lesions suitable for resection
4. 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
5. Participation in any clinical research study with administration of an investigational drug or therapy within 30 days prior to enrolment in the study
6. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment
7. 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
8. Prior radiation therapy of tumor/metastases
9. 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
10. Intake of immunomodulatory medication (Type 1 interferons)
11. 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
12. 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
13. 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
14. Live vaccine within 30 days prior to the first dose of study treatment
15. 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 (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic Treatment
16. History of interstitial lung disease
17. History of (non-infectious) pneumonitis that required steroids or current pneumonitis
18. History of anaphylaxis or severe drug hypersensitivity reactions
19. Active infection requiring systemic therapy
20. 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
21. 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
22. 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
23. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
24. 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
25. Women of childbearing potential: refusal or inability to use effective means of contraception
26. Contra-indication or known hypersensitivity to olaptesed pegol, polyethylene glycol, pembrolizumab or further ingredients to the investigational medicinal products
27. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
28. Previous enrolment in this clinical study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Window of Opportunity Monotherapy part:
Pharmacodynamics – changes in number, distribution and/or infiltration of immune cells characterized by surface marker expression in tumor metastases after treatment with olaptesed pegol
Combination therapy part:
Safety: Adverse events, laboratory findings/parameters |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Pharmacodynamicswill be evaluated at the end of the monotherapy phase, safety and efficacy at ther end of the study |
|
| E.5.2 | Secondary end point(s) |
Safety: Adverse events, laboratory findings/parameters
Pharmacodynamics – changes in the cytokine/chemokine signature of tumor metastases and in peripheral blood after treatment with olaptesed pegol
Combination therapy part:
Efficacy: Treatment response (RECIST 1.1, irRECIST), PFS, DCR, OS
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Pharmacodynamicswill be evaluated at the end of the monotherapy phase, safety and efficacy at ther end of the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| pharmacodynamics and safety |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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