An open label, dose escalation followed by dose expansion, safety and tolerability trial of CAN04, a fully humanized monoclonal antibody against IL1RAP, in subjects with solid malignant tumors.
- Conditions
- Solid malignant tumors10027656
- Registration Number
- NL-OMON50396
- Lead Sponsor
- Cantargia AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
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 <1.5xULN
* Hemoglobin >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
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 <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. Known history of autoimmune disorders, human immunodeficiency virus (HIV)
infection, or any other relevant congenital or acquired immunodeficiency.
Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C
(HCV) infection viral load. Note: Patients who have positive hepatitis B core
antibody or hepatitis B surface antibody can be enrolled but must have an
undetectable hepatitis B viral load. Patients who have positive hepatitis C
antibody must have an undetectable hepatitis C viral load.
12. Known bleeding disorder or coagulopathy.
13. Subjects with microbial or viral infection, which is not controlled by
appropriate 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 medication, depending on
the treatment arm. Also see section 6.1.10.1 * Contraception Methods.
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 compliance
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 monotherapy administered as 1st line.
18b Known tumor EGFR mutation, unless contraindication to EGFR-directed therapy.
18c Known tumor ALK rearrangements, unless contraindication to ALK-directed
therapy or ALK-directed therapy not available.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint for both parts of the study is as follows:<br /><br>The incidence of Grade 3 and higher adverse events (AEs) related to CAN04<br /><br>administration<br /><br>and according to the National Cancer Institute - Common Terminology Criteria<br /><br>for Adverse<br /><br>Events (CTCAE, version 4.03).</p><br>
- Secondary Outcome Measures
Name Time Method