Trial Title:
A Study Of IMM47 In Subjects With Advanced Solid Tumors
NCT ID:
NCT05985083
Condition:
Oncology
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
ADVANCED SOLID TUMORS
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IMM47
Description:
IMM47 is humanized mAb targeting CD24 to be administered via intravenous infusion every 2
weeks in 28-day treatment cycles.
Arm group label:
Dose escalation
Summary:
This is a first-in-human (FIH), open-label, multi-center, phase I study to evaluate the
safety, tolerance, pharmacokinetics (PK), immunogenicity, preliminary anti-tumor
activity, pharmacodynamics, and biomarker activity of IMM47 monotherapy in subjects with
advanced solid tumors.
Detailed description:
In phase Ia phase, approximately 17-48 eligible subjects with advanced solid tumors will
be enrolled, and an accelerated titration method and the traditional "3+3" design method
will be adopted to explore the safety, tolerability, PK, immunogenicity, and anti-tumor
activity of 6 dose levels of IMM47: 5 μg/kg, 50 μg/kg, 250 μg/kg, 1.0 mg/kg, 3.0 mg/kg
and 5.0 mg/kg or higher, to determine the MTD and RP2D.
Accelerated dose cohorts: At the dose cohorts of 5 μg/kg and 50 μg/kg, one subject will
be enrolled at first, and the conventional "3+3" design will be altered and the
additional 2 or 5 subjects would be enrolled if any ≥ Grade 2 drug related toxicities are
observed during the first 28-day cycle (DLT observational period).
"3+3" dose cohorts: Thereafter, at least three subjects will be enrolled in each dose
cohort at the 250 μg/kg, 1.0 mg/kg, 3.0 mg/kg and 5.0 mg/kg dose levels sequentially.
There will be a minimum interval of 48 hours between the 1st and 2nd subjects being dosed
in each "3+3" dose cohort. If no DLTs occur in a dose cohort of 3 subjects during the
first cycle (DLT observational period), 3 subjects will be enrolled at the next higher
dose level. If 1 of 3 subjects in a cohort experiences a DLT, an additional 3 subjects
will be enrolled at that dose level. If only 1 of 6 subjects experiences a DLT, then 3
subjects will be enrolled at the next higher dose level. If 2 or more subjects
experienced DLTs within a cohort, dose escalation will be halted and 3 more subjects will
be enrolled at the previous lower (tolerated) dose level until that cohort has 6
evaluable subjects. Depending on toxicity, the dose deescalation to an intermediate dose
may occur. Higher doses than 5.0 mg/kg may be explored under the decision of Safety
Review Committee (SRC). A total of 6 subjects must be enrolled at the MTD (or the highest
dose studied where no more than 1 of 6 subjects experiences a DLT if the MTD is not
identified) and evaluated at the end of Cycle 1 before any subject is dosed in the
expansion cohorts.
Continued dosing with IMM47 beyond the second cycle will be offered to subjects who do
not experience disease progression or significant toxicity. Subjects who are benefiting
from IMM47 will receive the treatment up to 12 cycles, at investigator's discretion.
Subjects discontinuing the study treatment early for any reason will complete an
end-of-treatment (EOT) visit within 30 (+7) days after the last dose, and a safety
follow-up visit within 90 (±7) days after the last dose. If the subjects who achieve
complete response (CR), partial response (PR), or stable disease (SD) with clinical
benefit discontinue the investigational product, the follow-up visits will be completed
every 12 weeks until disease progression, informed consent withdrawn by subject, death,
or loss to follow-up, or end of study (whichever occurs first). Survival follow-up will
be performed for a maximum of 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years at the time of signing the ICF.
2. With an expected life expectancy of ≥ 12 weeks.
3. With an ECOG performance status score of 0-1.
4. For phase Ia, subjects diagnosed histologically or cytologically with advanced
solidtumors (preferred but not limited to ovarian, esophageal, breast, lung,
colorectal, hepatocellular, pancreatic, urothelial, prostate, and head and neck
cancers) that have failed previous standard treatments or no standard treatment is
available.
5. The intervals for discontinuing the last anti-tumor therapy prior to the first dose
of the investigational product are required as follows Subjects who previously
received chemotherapeutic agents must have discontinued the drug for more than 3
weeks.
Subjects who previously received small-molecule targeted therapy must have
discontinued treatment for more than 2 weeks or 5 half-lives of the drug (whichever
is longer).
Subjects who previously received monoclonal antibodies (eg. CD20 antibody,
PD-1/PD-L1 antibody) must have discontinued the treatment for more than 4 weeks.
Subjects who previously underwent palliative radiation therapy must have
discontinued the treatment for more than 2 weeks.
6. With suitable organ and hematopoietic functions:
Neutrophil count ≥1.5 × 109/L. (no growth factor therapy within 4 weeks prior to
Screening).
Platelet count ≥100 × 109/L ; for subjects with HCC, platelet count ≥75 ×109 /L
Hemoglobin ≥ 90 g/L (subjects may be transfused >2 weeks before screening, but
should not be transfusion-dependent).
Total Bilirubin (TBIL) ≤ 1.5 × ULN (or ≤ 3.0 × ULN if subject has a documented
history of Gilbert's syndrome or liver metastases).
Both aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (or
both AST and ALT ≤ 5.0 × ULN if subject has a documented history of liver
metastases).
International normalized ratio (INR) ≤1.5 × ULN, or activated partial thromboplastin
time (APTT) ≤ 1.5× ULN.
Left ventricular ejection fraction (LVEF) ≥ 50%. Serum creatinine ≤1.5 × ULN or
creatinine clearance (CrCl) ≥ 40 mL/min (Cockcroft and Gault Equation) if serum
creatinine >1.5 ULN. Lower calculated creatinine clearance values may be allowed at
the Investigator's discretion and in consultation with the Medical Monitor and
Sponsor
7. Adverse events associated with previous anti-tumor therapies should have recovered
to ≤ Grade 1 (CTCAE version 5.0) (except for toxicities not considered a safety risk
such as alopecia, skin pigmentation, and other non-clinically significant
abnormalities).
8. Female subjects (based on sex assigned at birth) of childbearing potential must be
tested negative for serum pregnancy test during the screening period before
receiving the first administration of IMM47; any female subject of childbearing
potential must agree to take effective contraceptive measures during the entire
study and within 6 months after last dose of the investigational product. A subject
is considered to have childbearing potential if he/she is biologically capable of
having children and has a heterosexual sex life. Female subjects meeting at least
one of the following criteria are deemed to be without childbearing potential:
Has undergone hysterectomy or bilateral oophorectomy Medically confirmed with
ovarian failure Medically confirmed as postmenopausal (menstruation has stopped for
12 consecutive months not for pathological or physiological reasons)
Acceptable forms of contraception for female subjects are:
Should not have sexual intercourse or genital contact with a male partner, or use a
method of birth control for the duration of the study participation and for 6 months
last dose of the investigational product.
Must agree to use one form of contraception, including sterilization, combined
estrogen and progestogen containing hormonal contraception pills or an intravaginal,
transdermal, or intrauterine device.
Intrauterine hormone-releasing system. Bilateral tubal occlusion (surgical procedure
that involves blocking by cutting, burning or removing sections, or placing clips of
the fallopian tubes to prevent the ovum [egg] from being fertilized).
A vasectomized partner (surgical procedure that involves cutting and sealing the
tubes used to transport semen from the testicles to the penis, thereby rendering
infertility).
Male subjects with female partners of childbearing potential are eligible to
participate if they agree to ONE of the following for the duration of the study and
until 90 days after the last dose of the study treatment:
Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle
(abstinent on a long-term and persistent basis) and agree to remain abstinent.
Agree to use a male condom and have their partner use a contraceptive method with a
failure rate of <1% per year as described below when having penile-vaginal
intercourse with a WOCBP who is not currently pregnant.
In addition, male subjects must refrain from donating sperm for the duration of the
study and for 90 days after the last dose of study treatment.
Male subjects with a pregnant or breastfeeding partner must agree to remain
abstinent from penile-vaginal intercourse or use a male condom during each episode
of penile penetration for the duration of the study and until 90 days after the last
dose of the study treatment.
9. Subjects who voluntarily sign the informed consent form, understand the study, and
are willing to comply with the protocol, and are able to complete all trial
procedures.
10. At least one measurable or evaluable tumor lesion. For solid tumor: Measurable
lesion according to RECIST version 1.1 is defined as tumor lesions ≥10 mm in longest
diameter or pathologic node ≥ 15 mm in short axis.
11. For both phase Ia and Ib, subjects must agree to provide archived tumor tissue
samples for CD24 IHC expression assessment by the central laboratory. In the setting
where archival material is unavailable or unsuitable for use (e.g., recently
diagnosed subjects or diagnosed with fine needle aspiration), the subject must
consent and undergo fresh tumor biopsy (biopsy at acceptable risk as judged by the
Investigator). The requirement for fresh biopsy collected from a given subject could
be waived after the discussion with the Sponsor, if the tumor tissues are not safely
accessible as determined by the Investigator, or the tumor biopsies have to be
obtained from sites that require significant risk procedures.
Exclusion Criteria:
1. Subjects who previously received CD24 targeted therapy.
2. Prior allogeneic hematopoietic stem cell transplant or other organ transplants.
3. Subjects with known active central nervous system (CNS) metastases or primary CNS
Lymphoma. Stable previously treated CNS metastases in subjects who are asymptomatic
and have not been on corticosteroid therapy within 3 weeks prior to screening are
not considered to be active.
4. Subjects in need of immediate cytoreduction therapy.
5. Significant medical disease or conditions, as assessed by the Investigators and
Sponsor that would substantially increase the risk-benefit ratio of participating in
the study. This includes but is not limited to:
Uncontrolled hypertension (systolic BP > 160 mmHg or diastolic BP > 90 mmHg),
pulmonary hypertension, or unstable angina.
New York Heart Association (NYHA) Grade II or higher congestive heart failure.
History of myocardial infarction, or bypass surgery or stent placement within 6
months prior to the first dose of the investigational product.
Severe arrhythmia requiring treatment (except for atrial fibrillation or paroxysmal
supraventricular tachycardia that, according to the judgment of the investigators,
do not affect the study).
QTc interval > 450 ms for males and > 470 ms for females (Fridericia's Formula).
History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within
6 months prior to the first dose of investigational product.
Concurrent interstitial lung disease (ILD) (except for radiation therapy-induced
loco regional interstitial pneumonia), severe chronic obstructive pulmonary disease,
severe pulmonary insufficiency.
Diseases that may cause gastrointestinal bleeding or perforation. Known inherited or
acquired bleeding disorders Uncontrolled diabetes mellitus. Thoracoabdominal or
pericardial effusions that cannot be controlled by puncture and drainage and require
repeated drainage or with significant symptoms.
History of liver disease, including cirrhosis, alcoholic liver disease, etc.
6. Concurrent medical condition requiring systemic corticosteroids (prednisone daily
dose > 10 mg or equivalent dose) within 7 days prior to first dose of the
investigational product or during the study, or other immunosuppressive medications,
but not including locoregional corticoids by intranasal, inhalated or other routes
of administration, or physiological-dose corticoids systemic-therapy.
7. Known active infection including hepatitis B (known positive HBV surface antigen
(HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2
antibodies).
Subjects with a past or resolved HBV infection (defined as the presence of hepatitis
B core antibody [anti-HBc] and absence of HBsAg) are eligible.
Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase
chain reaction is negative for HCV RNA.
Subjects with HIV infection, and CD4+ T-cell (CD4+) counts < 350 cells/μL; or with
acquired immunodeficiency syndrome (AIDS) - defining opportunistic infections within
the past 12 months; or with uncontrolled opportunistic infections; or have an HIV
viral load >400 copies/mL.
8. Subjects with uncontrollable severe active infections (such as septicemia,
bacteremia, or viremia).
9. Subjects who received live attenuated vaccine within 4 weeks prior to the first dose
of the investigational product, or plan to receive attenuated vaccine during the
study.
10. Subjects who underwent a major surgery within 4 weeks prior to the first dose or
plan to undergo a major surgery in 3 months after receiving the investigational drug
(excluding catheterization, peripherally inserted central catheter, etc.).
11. Females who have a positive serum pregnancy test or who are lactating or planning to
become pregnant during the study or within 6 months after the last dose of
investigational product.
12. Received investigational therapy or used an investigational device within 4 weeks
prior to the first dose of study treatment
13. History of psychiatric illness or substance abuse likely to interfere with the
ability to comply with protocol requirements or giving informed consent
14. Prior malignancy active within the previous 3 years are not eligible for the trial
except for: locally curable cancers that have been apparently cured, such as basal
or squamous cell skin cancer, prostate cancer with evidence of undetectable Prostate
Specific Antigen (PSA) or carcinoma in situ of the prostate, cervix or breast.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Scientia Clinical Research Ltd, NSW
Address:
City:
Sydney
Zip:
2031
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Charlotte Lemech, Dr
Facility:
Name:
Macquarie University Clinical Trials Unit (MQ CTU)
Address:
City:
Syd
Zip:
2109
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Megan Crumbaker, Dr
Facility:
Name:
Icon Cancer Centre South Brisbane, QLD
Address:
City:
Brisbane
Zip:
4101
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Jim Coward, A Prof
Facility:
Name:
John Flynn Private Hospital
Address:
City:
Gold Coast
Zip:
4224
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
David Martin, Dr
Start date:
August 18, 2023
Completion date:
January 23, 2025
Lead sponsor:
Agency:
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Agency class:
Other
Collaborator:
Agency:
IQVIA RDS
Agency class:
Other
Source:
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05985083
