Status and phase
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About
This is a Phase 1/2, open-label, multicentric, non-randomised, parallel-arm study that aims to establish the safety, tolerability, and initial efficacy of CAN04 in combination with 3 SoC chemotherapies (mFOLFOX, DTX, and G/C).
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
PHASE 1 and PHASE 2:
PHASE 1 (Dose Escalation)
Subject has histologically or cytologically confirmed diagnosis of locally advanced cancer or metastatic cancer. Subjects do not need to have measurable disease per response evaluation criteria in solid tumours (RECIST) v1.1.
Subject has a condition where all standard therapeutic options with proven survival benefit have been exhausted, refused by the subject, or are contraindicated. OR Subject has a condition where 1 of the 3 study regimens (mFOLFOX, DTX, or G/C) is considered SoC for the next-line treatment.
Subject has additional disease characteristics per treatment arm:
PHASE 2 All treatment arms in Phase 2 (CRC, NSCLC or BTC)
CRC Arm
NSCLC Arm
Note: Subjects who received DTX monotherapy in a prior line of therapy are not eligible.
BTC Arm
Exclusion criteria
Subject has a known or suspected allergy to study drugs (including chemotherapy regimens), any of its components.
Subject has another histologically confirmed cancer different from those described in inclusion criteria, except for cervical carcinoma in situ, superficial non-invasive bladder tumour, curatively treated stage I non-melanoma skin cancer, or prostate cancer subjects curatively treated with surgery or radiation and not receiving systemic or androgen deprivation therapy. Subjects with a history of another cancer, different from that described in the inclusion criteria, can be enrolled if the cancer was curatively treated ≥5 years ago and non-recurrence has been documented in the past 2 years.
Subject has uncontrolled or significant heart failure defined as New York Heart Association Classification III or IV.
Subjects to receive mFOLFOX or DTX: having peripheral sensory neuropathy Grade ≥2.
Subject has QT interval corrected using Fridericia's formula (QTcF) >480 msec at screening.
Subjects to receive DTX and CAN04: if they have liver metastases and aspartate aminotransferase (AST) and/or ALT >1.5 × upper limit of normal (ULN) concomitant with alkaline phosphatase >2.5 × ULN.
Subject has uncontrolled brain metastases. Subjects are allowed to be enrolled if brain metastasis has been previously treated with surgery, and/or stereotactic radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of prednisone or equivalent) at the time of the first dose of CAN04. For asymptomatic subjects, without known brain metastases, brain imaging during screening is not required. Subjects with known brain metastases should have undergone brain imaging in the frame of the imaging screening procedures.
Subject has an active severe infection requiring parenteral antibiotics at the time of enrolment or subjects currently receiving oral antibiotics as a continuation of a previous course of parenteral antibiotics. Subjects can be enrolled when antibiotic treatment is complete and if there are no signs of residual infection. Note: Subjects with BTC who required stent placement should have the procedure completed 2 weeks before and be free of antibiotics (oral or parenteral) for at least 1 week before first treatment administration.
Subject has a history of a relevant autoimmune disease as per assessment of the investigator or autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day).
Subject is expected to require any other form of systemic or localised anti-neoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
Subject has had an allogeneic tissue/solid organ transplant.
Subject received a live vaccination, etanercept, or other tumour necrosis factor-alpha inhibitors prior to (within 28 days of first study drug administration) participation in this study. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, a wash-out of 2 weeks before first administration of study drug is recommended.
Subject had treatment with systemic anti-cancer treatments, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter. Subjects should have recovered from previous treatment toxicity to Grade 1, baseline (except alopecia and peripheral neuropathy).
Subject received radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for palliative irradiation to peripheral tumour lesions, other than for example spine or pelvis, without increased risk for delayed cytopenias) and has not recovered to Grade 1 or better from related toxicity of such therapy (except for alopecia).
Subject has known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load. Note: Subjects who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be included but must have an undetectable hepatitis B viral load.
Subjects who test positive for human immunodeficiency virus (HIV) are NOT excluded from this study but must meet the following criteria:
Subject has a known history of any other relevant congenital or acquired immunodeficiency other than HIV infection.
Subject has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Subject has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
Subject has any medical condition, co-morbidity, physical examination finding, metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the subject unsuitable for participation in a clinical study due to high safety risks and/or potential to affect interpretation of results of the study.
Subject has known allergy to any of the drugs or excipients in the allocated treatment.
Only subjects in the G/C arm: Subjects who, as per applicable local label, due to hearing impairment or ongoing phenytoin administration, have contraindication for cisplatin.
mFOLFOX Arm/CRC Arm Exclusion Criteria
Subjects with clinical laboratory test values at screening below the lower limit of normal for any of the following electrolytes: potassium, magnesium, corrected or ionised calcium.
Subjects with congenital long QT syndrome or a history of ventricular arrhythmias, including bradyarrhythmia (<50 beats per minute).
Subjects with existing uncompensated heart disease: myocardial ischaemia or early (up to 4 weeks) post-infarction status, congestive heart failure, left ventricular hypertrophy, cardiomyopathy, conduction disorder within 6 months before enrolment.
Subjects with dihydropyrimidine dehydrogenase (DPD) deficiency or who have been treated within 4 weeks of first dose of study treatment with potent DPD inhibitors (eg, brivudine, sorivudine). Subjects who previously received 5-FU without toxicity that can be correlated with DPD deficiency do not need to be tested
Subjects with pernicious anaemia or other anaemias due to vitamin B12 deficiency that cannot be corrected before the first dose of mFOLFOX.
Primary purpose
Allocation
Interventional model
Masking
40 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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