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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05985083




Registration number
NCT05985083
Ethics application status
Date submitted
30/07/2023
Date registered
14/08/2023
Date last updated
4/10/2023

Titles & IDs
Public title
A Study Of IMM47 In Subjects With Advanced Solid Tumors
Scientific title
A Phase I, Open-Label, Multicenter, Dose-Escalation And Cohort-Expansion Study Of IMM47 In Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
IMM47-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic Solid Tumors 0 0
Oncology 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IMM47

Experimental: Dose escalation - It's a dose escalation to identify the Maximum Tolerated dose (MTD) , recommended Phase II dose (RP2D) of IMM47, an accelerated titration method and the traditional "3+3" design method will be adopted. IMM47 will be sequentially escalated at the dose of 5 µg/kg,50 µg/kg, 250 µg/kg,1.0 mg/kg,3.0 mg/kg and 5.0 mg/kg or higher dose levels, administered via intravenous infusion every 2 weeks in 28-day treatment cycles.

The duration of the infusion is 120 min (± 10 min) for the 1st infusion and 60 min (± 5 min) for subsequent infusions.


Treatment: Drugs: IMM47
IMM47 is humanized mAb targeting CD24 to be administered via intravenous infusion every 2 weeks in 28-day treatment cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DLTs
Timepoint [1] 0 0
Baseline up to 28 days after the first dose
Primary outcome [2] 0 0
MTD(maximum tolerated dose)
Timepoint [2] 0 0
From start of treatment to treatment termination visit, up to 48 weeks
Primary outcome [3] 0 0
adverse events (AEs)
Timepoint [3] 0 0
Baseline up to 30 days after the last dose of study drug, up to 48 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/01/2025
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Other
Name
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT05985083
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Jim Coward, A/Prof
Address 0 0
Icon Cancer Centre South Brisbane, QLD
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Qiying Lu, Dr.
Address 0 0
Country 0 0
Phone 0 0
+86 21 38016387
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05985083