Solid malignant tumors
Conditions
Interventions
None listed
Sponsors
Cantargia AB
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Ability to understand and willingness to provide written informed consent before any trial-related activities. (Trial-related activities are any procedures that would not have been performed during normal management of the subject). 2. Age * 18 year. 3. Measurable disease in accordance to irRC (subjects enrolled prior to protocol version 7.0) or iRECIST (subjects enrolled after protocol version 7.0) by computed tomography (CT) or magnetic resonance imaging (MRI) scan. Imaging tests performed up to 2 weeks before ICF signature are valid for trial entry if they are performed with the same technique/equipment as the follow-up scans. 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 biologic/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 9.0 g/dL * Absolute neutrophil count >1000/µL in Part I and >1500/µL in Part II * Platelets >75x109/L for CAN04 monotherapy, and >100x109/L for the combination with chemotherapy (Arms C and D). * 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 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, unresectable, locally advanced or 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. All arms: Presence of tumor lesions amenable to biopsy and willingness to undergo repeat biopsies of these tumor lesions. It is not necessary to repeat the baseline biopsy procedure if: (i) there is enough archival material available, (ii) it has been preserved adequately, (iii) the subject did not receive any systemic anticancer treatment from the day of biopsy sampling and until the first dose of study drug, and (iv) if the sample is less than 60 days old from the treatment start. 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
Exclusion criteria
Exclusion criteria: 1. Known or suspected allergy to trial product or related product. 2. Subjects receiving live vaccination, etanercept or other TNF-* inhibitors or any 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 metastatic second malignancy. 5. Subjects with a life expectancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint for both parts of the study is as follows: 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints for both part of the study are as follows: Pharmacokinetics * Concentration at the end of infusion (Cinf end). * Maximum concentration (Cmax). * Time taken to reach maximum concentration (tmax). * Terminal half-life (t*). * 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 (sIL1RAP) will be assessed since it is a biomarker that may form immune complex with CAN04 and affect free concentration of CAN04. Additional pharmacokinetic endpoint for Part II: * Area under the curve from time 0 to tau (AUC0-*) Immunogenicity * Anti-Drug Antibodies (ADA) against CAN04. Preliminary signs of efficacy * Overall Response Rate (ORR) using irRC (Part I and Part II Arms A, B, and E), iRECIST (Part II, Arms C and D) and RECIST 1.1 (both Part I and II); with irRC (before protocol version 7.0) or iRECIST (from protocol version 7.0 onwards) 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 QoL as assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (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 LC13 (EORTC QLQ - LC13). | — |
Countries
Netherlands
Outcome results
None listed