| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Solid malignant tumors, in the following four indications;
Non-Small Cell Lung Cancer (NSCLC),
Pancreatic Ductal Adenocarcinoma (PDAC),
Triple negative Breast Cancer (TNBC) or
Colorectal Cancer (CRC) |
|
| E.1.1.1 | Medical condition in easily understood language |
Solid malignant tumors, in the following four indications;
Non-Small Cell Lung Cancer (NSCLC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Triple negative Breast Cancer (TNBC) or
Colorectal Cancer(CRC) |
|
| 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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065147 |
| E.1.2 | Term | Malignant solid tumor |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
Part I
• To define the Maximum Tolerated Dose (MTD) or Recommended Phase 2 dose (RP2D) of CAN04 once weekly (Q1W) in subjects with relapsed or refractory NSCLC, PDAC, TNBC or CRC.
Part II
• To determine the safety and tolerability of CAN04 at the RP2D in sub-jects with NSCLC or PDAC tumors, when given as monotherapy once weekly and once every 2 weeks (Q2W), and once weekly in combina-tion.
|
|
| E.2.2 | Secondary objectives of the trial |
• To assess pharmacokinetic (PK) parameters of CAN04.
• To assess anti-drug antibody (ADA) formation against CAN04.
• To determine preliminary signs of clinical efficacy of CAN04 as a single agent.
Additional secondary objectives for Part II
• To assess quality of life.
• To determine preliminary signs of clinical efficacy of CAN04 as a single agent and in combination.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Ability to understand and willingness to provide written informed consent before any trial-related activities. (Trial-related activities are any proce-dures that would not have been performed during normal management of the subject).
2. Age ≥ 18 year.
3. Measurable disease in accordance to irRC by computed tomography (CT) or magnetic resonance imaging (MRI) scan, no more than 6 weeks prior to screening.
4. At least 4 weeks since the last dose of chemotherapy, radiation therapy, immunotherapy, or surgery; at least 6 weeks for therapy which is known to have delayed toxicity; at least 4 weeks since treatment with biolog-ic/targeted therapies.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
6. Adequate bone marrow, hepatic, renal and coagulation function.
7. Clinical laboratory values at screening:
- Serum creatinine <1.5xULN
- Hemoglobin >9.0 g/dL
- Absolute neutrophil count >1000/µL in Part I and >1500/µL in Part II
- Platelets >75x109/L
- Total bilirubin <1.5x ULN
- Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤3x ULN (for subjects with hepatic metastases < 5x ULN)
- Prothrombin Time (PT) & Partial Thromboplastin Time (PTT) within 1.5x institutional ULN.
- In case there are no normal ranges available for the prothrombin time (PT) test, the international normalized ratio (INR) test may be used instead of PT. At screening, subjects should have an INR <1.5x ULN.
Additional inclusion criterion for Part I:
8. Subject with histologically or cytologically confirmed, unresectable, locally advanced or metastatic NSCLC, PDAC, CRC or TNBC tumor, relapsed or refractory to standard therapy or for which there is no standard therapy.
Additional inclusion criterion for Part II:
9. Arm A, Arm B and Arm E: Subjects with histologically or cytologically confirmed, locally
advanced, metastatic squamous or non-squamous NSCLC or PDAC,
relapsed or refractory to standard of care therapy or for whom there is
no standard therapy.
10. Presence of tumor lesions amenable to biopsy and willingness to
undergo repeat biopsies of these tumor lesions.
11. Arm C only:
11a: Subjects with histologically or cytologically confirmed diagnosis of
unresectable stage IIIB or stage IV squamous or non-squamous NSCLC
11b: Subjects must be eligible to receive a first line standard
chemotherapy regimen with cisplatin/gemcitabine or a second line
standard chemotherapy regimen with cisplatin/gemcitabine after
relapsing from first line with pembrolizumab monotherapy.
11c: Subjects who underwent (neo)adjuvant treatments are eligible if
the (neo)adjuvant treatment ended at least 6 months prior to inclusion.
12. Arm D only:
12a: Subjects with newly diagnosed, treatment naїve, histologically or cytologically
confirmed, unresectable, locally advanced or metastatic (stage III or
stage IV) PDAC.
12b: Subjects must be eligible to receive treatment with nab-paclitaxel
and gemcitabine.
12c: Subjects who underwent (neo)adjuvant treatments are eligible if
the (neo)adjuvant treatment ended at least 6 months prior to inclusion. |
|
| E.4 | Principal exclusion criteria |
1. Known or suspected allergy to trial product or related product.
2. Subjects receiving live vaccination, etanercept or other TNF-a inhibitors or other investigational agents during or just prior to (within 28 days of first study drug administration) participation in this study.
3. Previous participation in this trial (enrolled).
4. Clinical evidence of an active second malignancy.
5. Subjects with a life expectancy <12 weeks.
6. Uncontrolled or significant cardiovascular disease defined as New York Heart Association Classification III, or IV.
7. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
8. Not recovered from the adverse effects of prior therapy at the time of enrollment to ≤ grade 1, with the exception of alopecia grade 2.
9. Symptomatic brain metastases which are either untreated or uncontrolled by surgery and/or radiotherapy.
10. Immunocompromised subject currently receiving systemic therapy.
11. Subjects with history of HIV, hepatitis B or C exposure currently controlled by antiviral therapy.
12. Known bleeding disorder or coagulopathy.
13. Subjects with microbial or viral infection which is not controlled by appro-priate medication. Subjects with any type of chronic infection.
14. Women who are pregnant or breastfeeding.
15. Women of childbearing potential (WOCBP, defined as < 2 years after last menstruation and not surgically sterile) or men whose sexual partners are WOCBP who are unwilling or unable to use a highly effective method of contraception for at least 1 month prior to study entry, for the duration of the study, and for at least 3-6 months after the last dose of study medica-tion.
16. Evidence of serious uncontrolled medical disorder or active infection that, in the opinion of the Investigator or Medical Monitor, makes it undesirable for the subject to participate in the study or that would jeopardize compli-ance with the protocol.
17. Other medical conditions that in the opinion of the investigator disqualify the subject for inclusion.
18. Only for Arm C:
18a Prior lines of treatment with anti-cancer medication other than
pembrolizumab administered as 1st line.
18b Known tumor EGFR mutation, unless contraindication to EGFRdirected
therapy.
18c Known tumor ALK rearrangements, unless contraindication to ALKdirected
therapy or ALK-directed therapy not available. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part I and II
• The incidence of Grade 3 and higher adverse events (AEs) related to CAN04 administration and according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Ongoing during the complete trial. |
|
| E.5.2 | Secondary end point(s) |
Pharmacokinetics
• Concentration at the end of an injection/infusion (Cinf end).
• Maximum concentration (Cmax).
• Time taken to reach maximum concentration (Tmax).
• Terminal half-life (t½).
• Clearance (CL).
• Apparent volume of distribution during the terminal phase (Vz).
• Area under the curve from time 0 to infinity (AUC0-∞).
• Area under the curve from time 0 to time t (AUC0-t).
• Area under the curve from time 0 to time 24h (AUC0-24)
• Area under the curve from time 0 to time 168 h (AUC0-168)
• Mean residence time (MRT).
• Serum concentration of soluble IL1RAP.
Additional pharmacokinetic endpoint for Part II:
• Area under the curve from time 0 to tau (AUC0-t)
Anti-drug antibodies (ADA) against CAN04
• Anti-Drug Antibodies (ADA) against CAN04.
Preliminary signs of efficacy
• Overall Response Rate (ORR) using irRC and RECIST 1.1; with irRC to be the decision-making criteria.
• Duration of Response (DoR).
• Progression Free Survival (PFS) at 12 months and for the duration of the trial
• Overall Survival (OS) at 12, 24 and 36 months
Additional endpoints for Part II
• Health-related Quality of Life (HRQL) assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ C30; version 3.0).
• In addition and ONLY for subjects with NSCLC: Health-related QoL as
assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ - LC13). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Depending on the end point. Ongoing during the complete trial. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| 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 | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| 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 | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| In Part II: MTD once weekly versus MTD once every 2 weeks versus MTD once weekly/every 2 weeks + SOC |
|
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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