Metastatic colorectal cancer MedDRA version: 20.0 Level: LLT Classification code 10010036 Term: Colorectal carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: MGN1703
Product Code: MGN1703
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lefitolimod
CAS Number: 1548439-51-5
Current Sponsor code: MGN1703
Other descriptive name:
Sponsors
MOLOGEN AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Male or female patient 18 years or older 3. Histologically confirmed diagnosis of colorectal cancer presenting with unresectable stage IV (UICC) disease (primary tumor may be present) 4. Complete or partial response, as assessed by local investigators according to RECIST 1.1, within 12-30 weeks from start of induction treatment with standard first-line chemotherapy with or without biological agents 5. ECOG PS 0-1 6. Haematology and biochemistry laboratory results within the limits expected for a patient population recovering after receiving induction treatment: - Platelet count = 80x10 9/L - Leukocyte count = 1.50x10 9/L - Lymphocytes = 0.50x10 9/L - Haemoglobin = 9.0 g/dL or 5.59 mmol/L - Total bilirubin = 2.5 times the upper limit of normal (ULN) - AST = 3xULN in absence of liver metastases, or = 5.0xULN in presence of liver metastases - ALT = 3xULN in absence of liver metastases, or = 5.0xULN in presence of liver metastases - Serum creatinine = 2.0xULN 7. Male and female patients of childbearing potential (i.e. not post-menopausal for at least 24 consecutive months and did not undergo surgical sterilization – hysterectomy, bilateral tubal ligation, or bilateral oophorectomy for women, vasectomy for men) using an effective means of contraception with a failure rate of less than 1% per year, e.g. established use of oral, implanted or injected hormonal contraceptives; placement of intra-uterine device (IUD) or intra-uterine system (IUS); use of barrier methods such as condom or diaphragm together with spermicide product; true abstinence (when it is in line with preferred and usual lifestyle of the patient). Contraception will start after screening and continue throughout study until at least one month after the last dose of lefitolimod (MGN1703) or longer if required according to the SmPCs of the used standard therapy medications. Females of child bearing potential must have a negative serum pregnancy test. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 297 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 243
Exclusion criteria
Exclusion criteria: 1. History of other malignant tumors within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ 2. Known brain metastases (present or treated) 3. Contraindication to receiving lefitolimod (MGN1703) as per current investigator's brochure 4. Known hypersensitivity to any components of the study product 5. Prior allogeneic stem cell transplantation or organ transplantation. 6. Active or uncontrolled infections or undiagnosed febrile condition. 7. Severe anemia requiring repeated blood cell transfusion 8. Pre-existing autoimmune or antibody mediated diseases or immune deficiency 9. Chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks; continuous systemic steroid treatment within the last 2 weeks prior to start of study treatment 10. Use of systemic antibiotic therapy within the last 2 weeks prior to start of study treatment 11. Inadequate pulmonary function according to the investigator's judgment, history of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan 12. HIV seropositivity or active HBV/HCV infection 13. Serious concomitant disease or a medical condition that in the judgment of the investigator renders the patient at high risk of treatment complications 14. Female patient who is pregnant or breast feeding 15. Contraindication to receiving the planned standard maintenance treatment according to applicable SmPC 16. Treatment with any anti-cancer investigational drug within 12 months prior to study treatment or participation in another clinical study with other investigational drugs within 28 days prior to study treatment. 17. Vaccination within 1 month prior to start of study treatment 18. Any medical, mental, psychological or psychiatric condition that in the opinion of the investigator would not permit the patient to complete the study or understand the patient information
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the IMPALA trial is the evaluation of the efficacy of a novel switch maintenance treatment with lefitolimod (MGN1703) to increase overall survival (OS) in patients with metastatic colorectal cancer with tumor reduction after induction treatment with standard first-line chemotherapy, with or without biological agents.;Secondary Objective: The secondary objectives are efficacy parameters such as progression free survival and survival endpoints, toxicity and safety, tolerability, Quality of Life and patient related outcome (in participating study sites), and translational research.;Primary end point(s): The primary study endpoint is overall survival after randomization (OS), defined as the time between the date of randomization and the date of death from any cause.;Timepoint(s) of evaluation of this end point: The primary study endpoint is overall survival after randomization (OS), defined as the time between the date of randomization and the date of death from any cause. Measured by imaging (CT/MRI) at screening and throughout study according to local practice. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival from start of induction therapy (OSi) 2. Overall survival rates at 3, 4 and 5 years after Randomization 3. Progression free survival on study treatment (PFS on study) after randomization until second disease progression (PD) according to RECIST 1.1 (includes PFS1 and PFS2, see below). 4. Progression free survival after randomization until first PD, necessitating discontinuation of maintenance and re-introduction of all first-line chemotherapy agents (PFS1). 5. PFS after re-introduction of initial induction therapy until PD (usually followed by the start of a second line treatment) (PFS2) 6. Progression free survival after first-line treatment, including induction treatment before randomization, maintenance treatment and re-induction until subsequent PD (usually followed by the start of a second line treatment) (PFS3) 7. PFS rates at 2, 3, 4 and 5 years after randomization 8. Primary and secondary endpoints will also be analyzed by stratification criteria and by maintenance strategy. - Overall response rate (ORR = CR + PR) after randomization according to RECIST v1.1 . PFS will be assessed according to RECIST 1.1. 9. Responses and PD will be confirmed by independent radiological review for exploratory purposes only (the primary assessment will be that of the local investigators) 10. Adverse events (toxicity) according to NCI CTC AE v4.03 11. Quality of Life (QoL) assessment (EORTC QLQ C30 + CR29 and additional tools used locally) in selected study sites 12. Translational research a.) All randomized patients will participate in the immuno-monitoring plan. b.) Histopathological and biological markers information available at the centers will be collected. c.) The Study Steering Committee may also propose additional research projects for the sponsor's approval. Those selected for separate funding will be detailed in annex protocols submitted to local ethics committees for approval at participating institutions and will be cond | — |
Countries
Austria, Belgium, Estonia, Germany, Italy, Spain, United Kingdom
Contacts
Public ContactDirector Clinical Operations
MOLOGEN AG
Outcome results
None listed