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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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:
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
Primary outcome [4] 0 0
RP2D (recommended Phase 2 dose)
Timepoint [4] 0 0
From start of treatment to treatment termination visit, up to 48 weeks
Primary outcome [5] 0 0
serious adverse events (SAEs)
Timepoint [5] 0 0
Baseline up to 30 days after the last dose of study drug, up to 48 weeks
Secondary outcome [1] 0 0
Maximum Plasma Concentration (Cmax)
Timepoint [1] 0 0
48 weeks of treatment cycles
Secondary outcome [2] 0 0
Time to maximum concentration (Tmax)
Timepoint [2] 0 0
48 weeks of treatment cycles
Secondary outcome [3] 0 0
Elimination half-life (t1/2)
Timepoint [3] 0 0
48 weeks of treatment cycles
Secondary outcome [4] 0 0
Immunogenicity
Timepoint [4] 0 0
48 weeks of treatment cycles
Secondary outcome [5] 0 0
Overall Rate Response (ORR)
Timepoint [5] 0 0
When the last subject enrolled completes approximately 48 weeks of treatment
Secondary outcome [6] 0 0
Disease control rate (DCR)
Timepoint [6] 0 0
When the last subject enrolled completes approximately 48 weeks of treatment
Secondary outcome [7] 0 0
Duration of response (DoR)
Timepoint [7] 0 0
When the last subject enrolled completes approximately 48 weeks of treatment
Secondary outcome [8] 0 0
Progression-free Survival (PFS)
Timepoint [8] 0 0
When the last subject enrolled completes approximately 48 weeks of treatment
Secondary outcome [9] 0 0
AUC(0-tlast)
Timepoint [9] 0 0
48 weeks of treatment cycles
Secondary outcome [10] 0 0
AUC0-inf
Timepoint [10] 0 0
48 weeks of treatment cycles

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
N/A
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)
NSW,QLD
Recruitment hospital [1] 0 0
Scientia Clinical Research Ltd, NSW - Sydney
Recruitment hospital [2] 0 0
Macquarie University Clinical Trials Unit (MQ CTU) - Syd
Recruitment hospital [3] 0 0
Icon Cancer Centre South Brisbane, QLD - Brisbane
Recruitment hospital [4] 0 0
John Flynn Private Hospital - Gold Coast
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
2109 - Syd
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 0 0
4224 - Gold Coast

Funding & Sponsors
Primary sponsor type
Other
Name
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
IQVIA RDS
Address [1] 0 0
Country [1] 0 0

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/ct2/show/NCT05985083
Trial related presentations / publications
Public notes

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
qiying.lu@immuneonco.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05985083