Trial Title:
IMM2902 in Patients With Advanced Solid Tumors Expressing HER2
NCT ID:
NCT05805956
Condition:
Advanced Solid Tumor
Advanced Lung Cancer
Advanced Gastric Carcinoma
Advanced Cholangiocarcinoma
Conditions: Official terms:
Cholangiocarcinoma
Stomach Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IMM2902
Description:
a recombinant bispecific monoclonal antibody with high affinity to the dual targets, HER2
and CD47
Arm group label:
IMM2902
Summary:
This trial is an open-label, multicenter, first-in-human dose-escalation and cohort
expansion Phase I/II clinical study to evaluate the safety, tolerability and preliminary
efficacy of IMM2902 in the treatment of HER2-expressing advanced solid tumors
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily sign the Informed Consent Form (ICF) and follow the protocol
requirements;
2. Age ≥ 18 years old and ≤ 75 years old, regardless of gender;
3. Expected survival time ≥ 12 weeks;
4. HER2 expression:
HER2 protein expression or HER2 gene amplification was found in primary or
metastatic tumor tissue (IHC) or FISH.
Phase I (dose escalation phase):
HER2 expression is defined as IHC1+, IHC2+ or IHC3+, FISH testing is not required,
and testing results from local qualified medical institutions are acceptable.
Phase II (cohort expansion phase):
HER2 overexpression is defined as IHC 3+ or IHC 2+, which can be tested by local
qualified medical institutions.
5. Clinical diagnosis:
Phase I (dose escalation phase):
Patients with advanced solid tumors with HER2 expression (IHC1+, IHC2+ or IHC3+)
confirmed by histology or cytology, who have previously received standard treatment
progress, treatment ineffective or no standard treatment plan, including but not
limited to breast cancer, gastric cancer (including gastroesophageal combination
adenocarcinoma), urothelial carcinoma, biliary tract carcinoma, ovarian cancer,
colon cancer and non-small cell lung cancer.
Phase II (cohort expansion phase), including 3 cohorts:
Cohort 1: Histologically or cytologically confirmed unresectable locally advanced or
metastatic non-small cell lung cancer with HER2 overexpression (IHC3+ or IHC2+), who
have previously failed systemic therapy; Cohort 2: Unresectable locally advanced or
metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) with
histologically or cytologically confirmed HER2 overexpression (IHC3+ or IHC2+), who
have previously received at least two systemic regimens.
Cohort 3: Unresectable locally advanced or metastatic biliary tract cancer with
histologically or cytologically confirmed HER2 overexpression (IHC3+ or IHC2+),
recurrence or disease progression after previous standard treatment.
6. Patients included in the Phase II study need to provide previous HER2 test results,
or archive tumor tissue to detect HER2 expression status. If neither is available,
the patient may undergo a new tumor biopsy.
7. According to the evaluation criteria for solid tumors (RECIST v1.1), measurable
lesions (longest diameter of spiral CT scan ≥ 10 mm, if the lesion is a lymph node,
the short axis ≥ 15 mm; and the lesion has not received radiotherapy, unless the
lesion clear progress); Phase I (dose escalation phase): Evaluable lesions (target
lesions or non-target lesions); Phase II (Cohort Expansion Phase): Measurable
lesions (target lesions) according to RECIST v1.1 criteria.
8. Eastern Cooperative Oncology Group (ECOG) score 0 or 1;
9. Adequate organ and coagulation function
10. AE related to previous systemic chemotherapy, radical/extensive radiotherapy or
other antineoplastic drug treatment recovered to (NCI CTCAE v5.0)≤ Grade 1 (except
for non-clinically significant or asymptomatic laboratory abnormalities), Patients
with controlled grade 2 hypothyroidism and hyperglycemia may be enrolled after
consultation with the sponsor;
11. Cumulative dose of anthracycline doxorubicin ≤360mg/m2 or its equivalent dose,
epirubicin ≤720mg/m2;
10. Patients of childbearing age must take effective contraceptive measures during the
study to within 6 months after the last dose.
Exclusion Criteria:
1. Received the last systemic or local anti-tumor therapy within 4 weeks before the
first administration, including chemotherapy, immunotherapy, biological agents,
etc.; received hormone anti-tumor therapy, small molecule targeted therapy within 2
weeks before the first administration; Palliative local treatment for non-target
lesions within 2 weeks before the first administration; received non-specific
immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis
factor, etc., not including IL-11 for the treatment of thrombocytopenia); Chinese
herbal medicine or Chinese patent medicine with anti-tumor indications within 1 week
before the first administration.
2. Received therapeutic drugs targeting SIRPα/CD47 4 weeks before the first
administration, such as CD47 antibody, SIRPα fusion protein, SIRPα antibody and
SIRPγ fusion protein;
3. Patients with primary central nervous system (CNS) malignant tumors or active CNS
metastases who have failed local treatment (radiotherapy or surgery), but the
following patients are allowed to enroll: a. Asymptomatic brain metastases; b.
Clinical symptoms are stable (that is, there is no imaging progress 4 weeks before
the first administration, and any neurological symptoms have returned to the
baseline level), and corticosteroids and other treatments for brain metastases are
not required for ≥4 weeks;
4. Uncontrolled hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood
pressure ≥ 90mmHg) or pulmonary hypertension or unstable angina pectoris; myocardial
infarction or bypass or stent surgery within 6 months before administration; Chronic
heart failure history of grade III-IV of NYHA criteria; clinically significant
valvular disease; serious arrhythmia requiring treatment (except atrial
fibrillation, paroxysmal supraventricular tachycardia), including male QTc ≥ 450ms,
Female QTc≥470ms (calculated by Fridericia formula); cerebrovascular accident (CVA)
or transient ischemic attack (TIA) within 12 months before enrollment;
5. History of arterial thrombosis, deep vein thrombosis and pulmonary embolism within 3
months before the first administration;
6. Have a history of moderate or severe dyspnea at rest due to advanced malignant
tumors or their complications or severe primary lung diseases, or currently require
continuous oxygen therapy, or currently suffer from interstitial lung disease (ILD),
severe chronic obstructive pulmonary disease, severe pulmonary insufficiency,
symptomatic bronchospasm, etc.;
7. Suffering from other malignant tumors within 5 years before the first
administration. Except: a. Cervical carcinoma in situ or non-melanoma skin cancer
that has been radically cured; b. Second primary cancer that has been radically
cured and has no recurrence within five years; c. The investigators believe that
both primary cancers can benefit from this study;
8. Diseases that may cause gastrointestinal bleeding or perforation (such as duodenal
ulcer, intestinal obstruction, acute Crohn's disease, ulcerative colitis,
large-scale gastric and small intestinal resection, etc.); patients with chronic
Crohn's disease and patients with ulcerative colitis (except those with total colon
and rectal resection), even in the inactive phase, should be excluded; those with
hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis
syndrome; Perforation, intestinal fistula history, but not cured after surgical
treatment; esophageal and gastric varices;
9. Need puncture and drainage to treat uncontrollable pleural, abdominal and
pericardial effusions that require repeated drainage or have obvious symptoms;
10. Have active hepatitis B [hepatitis B virus surface antigen (HBsAg) positive and/or
hepatitis B virus antibody (HBcAb) positive, and HBV DNA ≥ 2000 IU/ml, and hepatitis
caused by drugs or other reasons is excluded], or active hepatitis C [anti-hepatitis
C virus (HCV) antibody positive, and HCV RNA is higher than the lower limit of
detection, and hepatitis caused by drugs or other causes is excluded];
11. Has a history of immunodeficiency, including human immunodeficiency virus (HIV)
infection, or other immunodeficiency diseases, or has a history of organ
transplantation;
12. Have a history of autoimmune diseases, including but not limited to systemic lupus
erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease,
Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis, etc.
patient. except:
1. Hypothyroidism that can be controlled only by hormone replacement therapy;
2. Skin diseases that do not require systemic treatment (such as vitiligo, and
psoriasis);
3. Controlled celiac disease. However, patients who are using immunosuppressants
or systemic hormone therapy (prednisone or other equivalent hormones at a dose
≥ 10 mg/day) and continue to use them within 2 weeks before enrollment cannot
be enrolled;
13. Evidence of uncontrollable severe active infection (such as sepsis, bacteremia,
viremia, etc.);
14. Have a history of allergies of grade 3 or above to any component or excipient of the
study drug; or have a history of allergic reactions of grade 3 or above to
trastuzumab or other anti-HER2 targeted drugs (CTCAE v5.0 classification);
15. Received anti-tumor vaccine treatment 4 weeks before the first administration or
plan to receive anti-tumor vaccine trial;
16. Have undergone major surgery within 4 weeks before the first administration and have
not fully recovered, or plan to undergo major surgery in the first 12 weeks after
receiving the study drug; have received minor surgery (including catheterization) 2
days before enrollment, except for central venous catheterization via peripheral
venipuncture);
17. Those who have a clear history of neurological or mental disorders, such as
epilepsy, dementia, and poor compliance;
18. Has a history of alcoholism or drug abuse in the past 1 year;
19. Serum pregnancy test positive or breastfeeding women; do not agree to take adequate
contraceptive measures during the study period and within 6 months after receiving
the test drug;
20. Patients who have participated in other clinical studies in the past shall be out of
the group in accordance with original clinical studies and more than 4 weeks prior
to the first administration of this study;
21. Other situations where investigators believe they are inappropriate for
participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
301 Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Jianming Xu
Facility:
Name:
Fudan University Cancer Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Jiong Wu
Start date:
February 15, 2022
Completion date:
October 2024
Lead sponsor:
Agency:
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
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/NCT05805956
