Trial Title:
IAH0968 in Combination With GC for the Treatment of HER2-Positive Unresectable Advanced/Metastatic Malignant Tumors
NCT ID:
NCT05991518
Condition:
HER2 Gene Mutation
Conditions: Official terms:
Neoplasms
Cisplatin
Gemcitabine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Investigator)
Intervention:
Intervention type:
Combination Product
Intervention name:
Injection of IAH0968+Gemcitabine+Cisplatin
Description:
Administration of IAH0968 is given once per cycle, with each cycle defined as every 3
weeks.
Arm group label:
Phase IIa - Clinical Exploratory Stage
Arm group label:
Phase Ia - Dose escalation
Other name:
IAH0968+GC
Intervention type:
Combination Product
Intervention name:
Gemcitabine+Cisplatin
Description:
Gemcitabine is administered at a dose of 1000 mg/m2 on the second day (D2) and ninth day
(D9) of each cycle. At least 6 hours after the completion of gemcitabine infusion,
cisplatin is administered at a dose of 70 mg/m2 on the second day (D2) of each cycle.
Arm group label:
Phase IIa - Clinical Exploratory Stage
Other name:
GC
Summary:
The study aims to evaluate the efficacy and safety of IAH0968 in combination with
gemcitabine and cisplatin for the treatment of HER2-positive unresectable
advanced/metastatic malignant tumors and cholangiocarcinoma. The study is divided into
two stages: Phase Ib, an open-label, non-randomized, multicenter dose-escalation trial,
and Phase II, a randomized, double-blind, parallel-controlled, multicenter trial.
Detailed description:
Phase Ib is an open-label, non-randomized, multicenter dose-escalation trial. It utilizes
the classic "3+3" design to investigate the safety and tolerability of IAH0968 in
combination with gemcitabine and cisplatin for the treatment of HER2-positive
unresectable advanced/metastatic malignant tumors and cholangiocarcinoma.
Phase II study is a randomized, double-blind, parallel-controlled, multicenter research
design. It aims to investigate the efficacy of IAH0968 in combination with gemcitabine
and cisplatin for the treatment of HER2-positive unresectable advanced/metastatic
malignant tumors and cholangiocarcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Phase Ib
1. The age of the participant should be 18 years or older.
2. The participant should have been diagnosed with HER2-positive advanced solid tumors
that have failed standard treatment, as confirmed by pathological histology or
cytology. Standard treatment failure is defined as disease progression during or
after the last treatment, or inability to tolerate treatment due to severe toxicity
(grade ≥ 4 hematologic toxicity or grade ≥ 3 non-hematologic toxicity following
previous standard treatment). HER2 positivity is defined as proven HER2-positive
through immunohistochemistry (IHC) staining and/or fluorescence in situ
hybridization (FISH). The interpretation and standards for HER2 positivity in breast
cancer will follow current breast cancer guidelines, and for HER2 positivity in
cancers other than breast cancer, current gastric cancer guidelines will be followed
(Appendix 9).
3. The GC regimen is the frontline standard treatment for the specific type of cancer
(including urinary tract carcinoma, NSCLC, pancreatic cancer, nasopharyngeal
carcinoma, etc.).
4. The participant should have at least one measurable lesion according to RECIST 1.1
criteria, and the measurable lesion should not have undergone any local treatment
(including local radiotherapy, ablation, and intervention therapy).
5. The ECOG performance status should be 0 or 1 (refer to Appendix 3).
6. During the screening phase, the participant's organ functions should be relatively
normal (upper limit of normal values based on the respective study center's range),
including:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- Hemoglobin (Hgb) ≥ 90 g/L
- Platelet count (PLT) ≥ 90 × 109/L
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 ×
upper limit of normal (ULN), or ≤ 5.0 × ULN for patients with liver metastasis
- Total bilirubin (TBIL) ≤ 1.5 × ULN
- Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min
calculated according to the Cockcroft-Gault formula (refer to Appendix 2)
- All premenopausal women and women within 12 months of menopause should have a
negative pregnancy test.
- Left ventricular ejection fraction (LVEF) ≥ 50%.
- Prothrombin time or international normalized ratio ≤ 1.5 × ULN, unless the
patient is receiving anticoagulant therapy.
If the patient has received platelet growth factors and/or granulocyte
colony-stimulating factors prior to the above examinations, a washout period of at
least 1 week is required.
7. The expected survival period should be ≥ 3 months.
8. The patient should agree to use at least one medically acceptable contraceptive
method during the study treatment period and within 6 months following the end of
the study treatment (for women: intrauterine device, oral contraceptives, or
condoms, etc.; for men: condoms, abstinence, etc.), and female patients should not
be lactating.
The patient should have full understanding of the study content, procedures, and
potential risks and benefits, and should sign the informed consent form. The patient
should demonstrate good compliance and be able to cooperate with the study and follow-up.
Phase IIa
1. The age of the participant should be 18 years or older.
2. The participant should have been diagnosed with locally advanced or metastatic
HER2-positive BTC (biliary tract cancer) confirmed by pathological histology or
cytology, and should not have received systemic chemotherapy treatment.
3. The participant should have at least one measurable lesion according to RECIST 1.1
criteria, and the measurable lesion should not have undergone any local treatment
(including local radiotherapy, ablation, and intervention therapy).
4. The ECOG performance status should be 0 or 1 (refer to Appendix 3).
5. During the screening phase, the participant's organ functions should be relatively
normal (upper limit of normal values based on the respective study center's range),
including:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- Hemoglobin (Hgb) ≥ 90 g/L
- Platelet count (PLT) ≥ 90 × 109/L
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 ×
upper limit of normal (ULN), or ≤ 5.0 × ULN for patients with liver metastasis
- Total bilirubin (TBIL) ≤ 1.5 × ULN
- Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min
calculated according to the Cockcroft-Gault formula (refer to Appendix 2)
- All premenopausal women and women within 12 months of menopause should have a
negative pregnancy test.
- Left ventricular ejection fraction (LVEF) ≥ 50%.
- Prothrombin time or international normalized ratio ≤ 1.5 × ULN, unless the
patient is receiving anticoagulant therapy.
6. The expected survival period should be ≥ 3 months.
7. The patient should agree to use at least one medically acceptable contraceptive
method during the study treatment period and within 6 months following the end of
the study treatment (for women: intrauterine device, oral contraceptives, condoms,
etc.; for men: condoms, abstinence, etc.), and female patients should not be
lactating.
The patient should have full understanding of the study content, procedures, and
potential risks and benefits, and should sign the informed consent form. The patient
should demonstrate good compliance and be able to cooperate with the study and follow-up.
Exclusion Criteria:
Phase Ib
1. Known hypersensitivity reaction to any monoclonal antibody or a documented history
of allergies to gemcitabine or cisplatin and its components.
2. Previous treatment: (1) Not recovered from adverse reactions caused by previous
anti-tumor treatment to normal levels (according to CTCAE 5.0, hematologic toxicity
≥ Grade 2, non-hematologic toxicity ≥ Grade 1), excluding radiation-induced late
toxicities considered irreversible by the investigator such as alopecia and skin
pigmentation. (2) Patients who have received treatment with trastuzumab/pertuzumab
and their biosimilars (mono-therapy, combination chemotherapy, ADC drugs, bispecific
antibodies, etc.) within 4 weeks prior to enrollment. (3) Patients who have
participated in other clinical trials within 4 weeks prior to enrollment and have
used investigational drugs during this period. (4) Patients who have previously
received GC regimen treatment for anti-tumor therapy and experienced relapse due to
drug resistance.
3. Previous allogeneic hematopoietic stem cell transplantation or solid organ
transplantation.
4. Surgical procedures within 4 weeks prior to enrollment, and the investigator
considers that the patient's condition has not recovered to a level allowing for
initiation of this study treatment (excluding previous diagnostic biopsies and
biliary stent placement/percutaneous transhepatic cholangiographic drainage
procedures performed to relieve bile duct obstruction [PTBD]).
5. Vaccination with live vaccines within 4 weeks prior to enrollment, or receipt of
blood transfusion within 2 weeks.
6. Radiotherapy other than focal palliative bone radiotherapy within 4 weeks prior to
enrollment.
7. Clinical symptoms of central nervous system metastasis within 4 weeks prior to
enrollment. Patients with previous treatment for brain or meningeal metastases may
be included if the clinical condition is stable for at least 2 months and systemic
steroid therapy (dose > 10 mg/day prednisone or equivalent) has been discontinued
for ≥ 4 weeks.
8. Hospitalization or inability to undergo study treatment within 30 days prior to
randomization due to exacerbation of chronic obstructive pulmonary disease or other
respiratory diseases.
9. Liver transplant candidates and patients who can undergo transplantation during a
medically acceptable period.
10. Exclusion of early-stage cancers (other than those treated with curative intent
within 5 years before signing the informed consent), including but not limited to in
situ cervical cancer, superficial noninvasive bladder cancer, basal cell carcinoma,
and in situ squamous cell carcinoma, or gastrointestinal tumors limited to the
mucosal layer and already resected under endoscopy.
11. Presence of severe or poorly controlled diseases, including but not limited to: (1)
myocardial infarction, clinically significant arrhythmias requiring treatment,
congestive heart failure, myocarditis, and angina pectoris occurring within 6 months
prior to enrollment. (2) Hepatitis B virus (HBV) infection with positive HBV DNA
(≥1.0×104 copies/mL or ≥2000 IU/mL), hepatitis C virus (HCV) infection with positive
HCV RNA (>1.0×103 copies/mL or >100 IU/mL), and positive human immunodeficiency
virus (HIV) test. (3) Active tuberculosis (clinical symptoms, physical examination
findings, or radiographic evidence of active tuberculosis). (4) Severe and
uncontrolled pulmonary diseases (severe infectious pneumonia, interstitial lung
disease, etc.) (≥ Grade 3 CTCAE). (5) Uncontrolled biliary infection. Biliary
obstruction should be relieved by endoscopic or percutaneous transhepatic biliary
drainage (PTBD). Patients with biliary obstruction should have sufficient biliary
drainage and no evidence of ongoing infection at the time of enrollment and on Day 1
of Cycle 1 without antibiotic treatment. (6) Severe infections of any type that are
uncontrolled (≥ Grade 3 CTCAE). (7) Presence of ascites, pleural effusion, or
pericardial effusion requiring drainage before the first study drug treatment.
Presence of other conditions considered inappropriate for participation in this study by
the investigator.
Phase IIa
1. Known hypersensitivity reaction to any monoclonal antibody.
2. History of allergy to gemcitabine or cisplatin and its components.
3. Recent surgery within 4 weeks prior to enrollment, with the patient's condition
considered inadequate for starting the study treatment (excluding prior diagnostic
biopsies and percutaneous transhepatic biliary drainage PTBD for relieving bile duct
obstruction).
4. Vaccination with any live vaccines within 4 weeks prior to enrollment or receipt of
blood transfusion within 2 weeks.
5. Radiation therapy received within 4 weeks prior to enrollment, excluding focal
palliative bone radiation.
6. Detection of clinically symptomatic central nervous system metastasis within 4 weeks
prior to enrollment. Prior treatment for brain or meningeal metastasis is allowed if
clinically stable for at least 2 months and has stopped systemic steroid therapy
(dose >10 mg/day prednisone or equivalent) for ≥4 weeks.
7. Hospitalization or inability to initiate study treatment due to exacerbation of
chronic obstructive pulmonary disease or other respiratory diseases within 30 days
prior to randomization.
8. Liver transplant candidates and patients who are eligible for transplantation within
a medically acceptable time frame.
9. Exclusion of early-stage cancers treated with curative intent within the past 5
years or mucosal cancers limited to gastroenteric mucosa and treated by endoscopic
resection.
10. Presence of severe or poorly controlled diseases, including but not limited to: a)
occurrence of myocardial infarction, clinically significant cardiac arrhythmias
requiring treatment, congestive heart failure, myocarditis, or angina within 6
months prior to enrollment; b) Hepatitis B virus (HBV) infection with positive HBV
DNA (≥1.0×104 copies/mL or ≥2000 IU/mL), hepatitis C virus (HCV) infection with
positive HCV RNA (>1.0×103 copies/mL or >100 IU/mL), or positive human
immunodeficiency virus (HIV) test; c) active tuberculosis (clinical symptoms,
physical examination findings, or radiographic evidence of active tuberculosis); d)
severe and uncontrolled pulmonary disease (severe infectious pneumonia, interstitial
lung disease, etc.) (≥CTCAE Grade 3); e) uncontrolled biliary infection. Biliary
obstruction should be relieved by stent placement or percutaneous transhepatic
biliary drainage (PTBD). Patients with biliary obstruction should have adequate
biliary drainage, with no evidence of ongoing infection on the day of enrollment and
Day 1 of Cycle 1, without receiving antibiotic treatment; f) uncontrolled severe
infections of any kind (≥CTCAE Grade 3); and g) presence of ascites, pleural
effusion, or pericardial effusion requiring drainage prior to initial study drug
treatment.
Other conditions deemed inappropriate for participation in this study, as determined by
the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Affiliated Zhongshan Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Liu Tianshu, M.D.
Start date:
April 25, 2023
Completion date:
December 2025
Lead sponsor:
Agency:
SUNHO（China）BioPharmaceutical CO., Ltd.
Agency class:
Industry
Source:
SUNHO（China）BioPharmaceutical CO., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05991518
