Trial Title:
Safety of AM-928 Infusion in Advanced Solid Tumors
NCT ID:
NCT05687682
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Solid tumor
EpCAM
Antibody
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
AM-928
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
AM-928
Description:
AM-928, which is a humanized anti-EpCAM monoclonal antibody developed by AcadeMab
Biomedical Inc.
Arm group label:
Level -1
Arm group label:
Level 1
Arm group label:
Level 2
Arm group label:
Level 3
Arm group label:
Level 4
Arm group label:
Level 5
Arm group label:
Level 6
Summary:
This is a Phase I, open-label, dose-escalation study for a novel cancer treatment,
AM-928, intravenous infusion antibody for advanced solid tumor. The study is aimed to
learn the safety, tolerability, pharmacokinetics, and preliminary efficacy profile of
AM-928.
The dose escalation strategy will adopt accelerated titration combined with a Bayesian
optimal interval (BOIN) design. Seven dose levels are designed and each participant will
be assigned to a specific dose regimen depending on the time of enrollment. In the study,
each participant will receive AM-928 treatment cycles till meeting any treatment
discontinuation criterion and be followed for safety and long-term survival.
The whole study is expected to take approximately three years to complete.
Detailed description:
This is a first-in-human Phase I, open-label, dose-escalation study to investigate the
safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of AM-928 infusion
in subjects with advanced solid tumors in multiple sites in Taiwan.
Eligible subjects will be dosed with different dosages of AM-928 in 1 of the 7 dose
levels (0.1, 0.3, 1, 3, 6, 10, 15 mg/kg). Dose levels will be escalated from dose Level 1
at 0.3 mg/kg to Level 6 at 15 mg/kg of AM-928 (or may be de-escalated to Level -1 at 0.1
mg/kg), which will be administered (intravenous infusion) once weekly (QW) for 4 weeks
(D1, D8, D15, D22) as a treatment cycle until any treatment discontinuation criterion is
met. Basically, there will be no breaks between dosing cycles. From Cycle 4,
intra-subject dose escalation may be applied if supported by preliminary safety and PK
data.
The dose escalation strategy will adopt accelerated titration combined with a Bayesian
optimal interval (BOIN) design. The accelerated titration will be adopted for 0.3 mg/kg,
while the BOIN design will be adopted for other dose levels, including 1 mg/kg, 3 mg/kg,
6 mg/kg, 10 mg/kg, and 15 mg/kg. In the "accelerated titration" stage, if any ≥ Grade 2
adverse event occurs, the current and subsequent dose groups will be changed to the BOIN
dose escalation method. The target toxicity rate for the maximum tolerated dose (MTD) is
ϕ= 0.3, and the maximum sample size is determined to be 30, maximum of 9 subjects per
dose level. A cohort size of 3 and a maximum cohort number of 3 for each dose level will
be adopted for subject recruitment. The dose escalation may end when one of the following
criteria is met: (1) The planned sample size of 30 has been reached; (2) 9 subjects have
been treated and evaluable for DLT at the next intended dose level (should not exceed 9
subjects at one dose level); (3) all doses explored appear to be overly toxic, and the
MTD cannot be determined.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female, age ≥ 18 years
2. Histologically/cytologically confirmed, locally advanced unresectable or metastatic
solid tumors that are refractory to or intolerant of existing standard therapy, for
which no effective standard therapy that confers clinical benefit is available
3. Availability of archival tissue specimens for EpCAM immunohistochemistry (IHC)
staining. Tumor tissues acceptable include:
- Tumor tissue sample collected at the time of initial diagnosis
- The most recent available metastatic tumor biopsy tissue if available (a
pre-treatment biopsy may be obtained if the biopsy site is safely accessible)
4. Has at least one measurable lesion according to Response Evaluation Criteria in
Solid Tumors (RECIST) version 1.1
5. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
6. Subject's life expectancy of at least 12 weeks
7. Has adequate hematopoietic, coagulation, hepatic function and renal function:
- Hemoglobin ≥ 8.0 g/dL without transfusion or erythropoiesis stimulating agent
support within 1 week
- Absolute neutrophil count (ANC) ≥ 1,500 cells/μL without WBC growth factor
support within 1 week
- Total white blood cell (WBC) ≥ 2,500 cells/μL
- Platelet ≥ 80,000 counts/μL without transfusion support within 1 week
- International normalized ratio (INR) and activated partial thromboplastin time
(APTT) ≤ 1.5 upper limit of normal (ULN)
- Total bilirubin ≤ 1.5× ULN and no sign of jaundice (≤ 3× ULN for subjects with
known Gilbert disease)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3× ULN (≤
5× ULN for subjects with tumor involvement in liver)
- Serum albumin ≥ 3.0 g/dL
- eGFR (CKD-EPI) ≥ 60 mL/min/1.73 m^2
8. A female subject with childbearing potential should be confirmed of not being
pregnant or not lactating at the screening and during the study
9. Willingness and ability to comply with protocol-stated requirements, instructions,
and restrictions in the investigator's judgement
10. Is able to understand the nature of this study and accepts to enter the study by
signing written informed consent
Exclusion Criteria:
1. Received any localized cancer therapeutic modalities (e.g., surgery on target
lesions, radiotherapy) within 4 weeks prior to initial dosing (except the palliative
radiotherapy performed on non-target local lesions), or have any unrecovered
surgical wound (except the wound from the biopsy at screening)
2. Received anti-tumor chemotherapy, small molecular targeted therapy, hormone therapy
(except hormone replacement therapy or oral contraceptives), biological product
therapy (mAbs, bispecific antibody, and ADC), or other anti-cancer agents within 2
weeks or 5 half-lives (whichever is shorter) before the first AM-928 dosing;
received immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) before
the first AM-928 dosing.
3. Carries history of primary malignancy other than the entry diagnosis that could
affect compliance with the protocol or interpretation of results within 3 years
prior to the Screening Visit, except curatively treated non-melanoma skin cancer,
cervical carcinoma in situ, or superficial bladder tumors
4. Received immunosuppressive medication(s) (including, but not limited to, steroids,
cyclophosphamide, azathioprine, methotrexate, thalidomide, tumor necrosis factor-ɑ
antagonists, and calcineurin inhibitors) within 2 weeks (for those half-life ≤ 72
hours) or 4 weeks (for those half-life > 72 hours) prior to study dosing and during
the study period, with the following caveats:
- For steroids, ≤10 mg of prednisone per day or equivalent is allowed
- Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is
allowed. For a subject under long-term treatment of a concurrent
disease/status, the dose should be stable (i.e., no change or decreasing dose)
within 3 months prior to C1D1
- The use of inhaled corticosteroids is allowed if they are on a stable dose
(i.e., no change or decreasing dose within 3 months prior to C1D1)
- The use of oral mineralocorticoids is allowed
- Physiologic doses of corticosteroids for adrenal insufficiency or supportive
care for a subject's advanced tumor may be allowed at the investigator's
discretion
5. Subject with significant cardiopulmonary abnormalities as defined by:
- Poorly controlled hypertension (systolic blood pressure > 150 mm-Hg and/or
diastolic blood pressure > 100 mm-Hg on anti-hypersensitive medications)
- Left ventricular ejection fraction (LVEF) < 50% at screening
- History of symptomatic congestive heart failure > class 2 per New York Heart
Association (NYHA) classification
- History of myocarditis
- Myocardial ischemia/infarction or unstable angina within 6 months of study
enrollment
- Uncontrolled serious cardiac arrhythmias
- Corrected QT interval > 470 ms demonstrated by at least 2 ECGs > 30 minutes
apart
- Evidence of active pneumonitis (including drug-induced), organizing pneumonia
(i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or
history of idiopathic pulmonary fibrosis. History of radiation pneumonitis in
the radiation field (fibrosis) is permitted.
- History of 2nd or 3rd-degree atrioventricular conduction defects
6. History of thromboembolic or cerebrovascular events within the last 6 months at
screening, including transient ischemic attack, cerebrovascular accident, or deep
vein thrombosis
7. Prior treatment with any EpCAM-targeted anti-cancer therapies
8. Subjects with the following infections:
- History of active pulmonary tuberculosis infection ≤ 48 weeks prior to C1D1,
regardless of treatment
- Any major episode of infection requiring treatment with systemic antibiotics or
hospitalization within 2 weeks prior to C1D1
- Known human immunodeficiency virus (HIV) history
- Presence of hepatitis B surface antigen (HBsAg) with HBV viral load > 2000
IU/mL (HBsAg-positive subjects with HBV viral load ≤ 2000 IU/mL are eligible.
These subjects should continue to receive antiviral treatment during the study
treatment and follow local HBV antiviral treatment standards after the study
treatment during the study)
- HCV RNA positive (subjects with a history of HCV infection are eligible if
their HCV viral load cannot be detected at screening; curative antiviral
therapy should have been completed at least 4 weeks before C1D1)
9. Administration of a live, attenuated vaccine within 4 weeks before C1D1 or
anticipation that such a live, attenuated vaccine will be required during the study
10. Received any investigational product within 4 weeks before C1D1
11. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
humanized antibodies
12. Known hypersensitivity to any of the components of AM-928
13. Has unstable/uncontrolled central nervous system (CNS) malignancy, leptomeningeal,
or brain metastasis (progressing or those who continue to require glucocorticoids or
intrathecal chemotherapy)
14. Has symptomatic pleural effusion, pericardial effusion, or poorly controlled ascites
15. Suffering from side/toxic effects of previous or current therapy [i.e., National
Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE) ≥ Grade
2] that, judged by the investigator, may interfere with the trial results or the
subject's safety
16. Prior allogeneic stem cell, solid organ, or bone marrow transplantation
17. Subject with any underlying medical, mental, or psychological conditions that would
impair the treatment compliance, contraindicate the use of the investigational
product, or that may render the subject at high risk from treatment complications,
in the opinion of the investigator, would not permit to participate in the study
18. All male subjects and female subjects with childbearing potential (between puberty
and 1 year after menopause) should use at least one of the appropriate contraception
methods shown below from signing ICF to at least 4 months or 5 half-lives (if data
available), whichever is longer, after stopping study treatment.
1. Total abstinence (when this is in line with the preferred and usual lifestyle
of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception.
2. Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before
taking study treatment. In the case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow up hormone level
assessment.
3. Male sterilization (at least 6 months prior to screening). For female subjects
on the study, the vasectomized male partner should be the sole partner for that
subject.
4. Combination of any two of the following listed methods: (d.1+d.2 or d.1+d.3, or
d.2+d.3):
d.1. Use oral, injected, or implanted hormonal methods of contraception or other
forms of hormonal contraception that have comparable efficacy (failure rate <1%),
for example, hormone vaginal ring or transdermal hormone contraception.
d.2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). d.3.
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Taiwan University Hospital
Address:
City:
Taipei
Zip:
10002
Country:
Taiwan
Status:
Recruiting
Start date:
July 14, 2023
Completion date:
June 2026
Lead sponsor:
Agency:
AcadeMab Biomedical Inc.
Agency class:
Industry
Source:
AcadeMab Biomedical Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05687682
