Trial Title:
A Clinical Trial to Evaluate Effect of IAP0971 in Patients With Advanced Malignant Tumors
NCT ID:
NCT06581419
Condition:
Advanced Malignant Neoplasm
Advanced or Metastatic Non-small Cell Lung Cancer
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IAP0971
Description:
Subjects receive IAP0971, which will be administered every 3 weeks in a 3-week cycle.
Arm group label:
phase I
Arm group label:
phase II
Summary:
Phase I: To evaluate the safety, tolerance and effectiveness of IAP0971 for the treatment
of advanced malignant tumors.
Phase II: Evaluation of IAP0971 therapy driver negative and PD-L1 positive (TPS≥50%) The
initial treatment is effective in subjects with advanced or metastatic non-small cell
lung cancer.
Detailed description:
The study includes dose-escalation (Phase I) and dose-expansion (Phase II) clinical
trials. Phase I clinical trials will be conducted first. After completing the
dose-escalation phase, the plan is to determine the recommended Phase II dose (RP2D) in
the maximum tolerated dose (MTD) group and proceed with the subsequent Phase II
exploratory studies.
The objective of the Phase I dose-escalation phase is to preliminarily assess the safety
and tolerability of IAP0971 and to determine the MTD based on the incidence of
dose-limiting toxicities (DLTs) in each dose group. Phase II will use an open-label,
non-randomized, single-arm, multicenter design. The study will evaluate adverse events
and adverse reactions through clinical observation, vital sign monitoring, and laboratory
tests. Tumor assessments will be conducted using RECIST 1.1 criteria: within 48 weeks of
the first infusion of the investigational drug, assessments will be performed after every
two cycles (±7 days), and after 48 weeks, assessments will occur every four cycles (±7
days) until disease progression, initiation of new anti-tumor therapy,
investigator-determined ineligibility (e.g., intolerable adverse reactions), loss to
follow-up, voluntary withdrawal, death, or study termination/suspension.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age of 18-75 years old (including cut-off value), regardless of gender.
2. Phase I only: patients with histologically confirmed advanced or metastatic
malignant solid tumors who have failed to respond to standard treatment, who have no
standard treatment options, who are not currently applicable to standard treatment,
or who have been assessed by the investigator to benefit from this treatment.
3. Phase II only: patients with histologically confirmed locally advanced (stage IIIB
or IIIC) or metastatic (stage IV) non-small cell lung cancer (NSCLC) that is not
amenable to complete surgical resection and definitive concurrent chemoradiotherapy.
Note: For patients with locally advanced stage (stage IIIB/IIIC) who cannot accept
radical concurrent/sequential chemoradiotherapy, they need to be evaluated by
relevant professional physicians and confirmed by written records.
4. Phase II only: no prior systemic antitumor therapy for locally advanced or
metastatic NSCLC (except for patients who received adjuvant/neoadjuvant chemotherapy
or definitive concurrent or sequential chemoradiotherapy for locally advanced
disease and disease progression ≥6 months after the last treatment).
5. Phase II only: PD-L1 positive (TPS≥50%) as determined by IHC, and patients were
negative for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase
(ALK) by immunohistochemistry.
6. have at least one measurable lesion according to RECIST 1.1 criteria (tumor lesion
located in the previous radiotherapy area or other locoregional treatment site,
generally not considered a measurable lesion unless the lesion has clearly
progressed or persists beyond three months of radiotherapy).
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. predicted survival time ≥3 months.
9. with adequate organ function:
① Blood system (no blood transfusion or hematopoietic stimulation therapy within 14
days) : absolute neutrophil count (ANC) ≥1.5×109/L, platelet count (PLT) ≥100×109/L,
hemoglobin (HGB) ≥90 g/L; ② Liver function: total bilirubin (TBIL) ≤1.5 times the
upper limit of normal value (ULN), except Gilbert's syndrome Out of; Aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 times ULN, and
patients with liver metastasis or liver cancer need AST and ALT≤5.0 times ULN and
total bilirubin ≤3.0 times ULN;
② Renal function: serum creatinine (Cr) ≤1.5 times ULN; If creatinine > 1.5 times
ULN, creatinine clearance (Ccr) ≥50 mL/min (calculated by Cockcroft-Gault formula)
was required.
③ Coagulation function: prothrombin international normalized ratio (INR) ≤1.5 times
ULN, activated partial thromboplastin time (APTT) ≤1.5 times ULN, patients with
liver metastasis or liver cancer need INR and APTT≤2.5 times ULN.
10. Eligible patients (men and women) of childbearing potential must consent to use a
reliable method of contraception (hormonal or barrier methods or abstinence) with
their partner during the trial and for at least 6 months after the last dose; Female
patients of reproductive age had to have a negative blood pregnancy test within 7
days before the first use of the study drug.
11. Subjects must give informed consent for this study and voluntarily provide written
informed consent before the trial.
Exclusion Criteria:
1. Phase II only: small cell lung cancer or sarcomatoid lesion confirmed by
histopathology.
2. Phase II only: previous immunotherapy, including immune checkpoint inhibitors (e.g.,
anti-PD-1 /PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists
(e.g. ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immune cell therapy, and any
treatment targeting the mechanism of tumor immune action.
3. Phase I only: patients received anti-tumor therapy such as systemic chemotherapy,
radiotherapy, biological therapy, endocrine therapy, or immunotherapy within 4 weeks
before the first dose of study drug; The following drugs were excluded according to
the following criteria:
① Treatment with a small-molecule tyrosine kinase inhibitor within 2 weeks before
the first dose;
② Palliative local treatment for non-target lesions within 2 weeks before the first
dose; Patients received non-specific immunomodulatory therapy (such as interleukin,
interferon, thymosin, not including IL-11) within 2 weeks before the first dose;
③ received Chinese herbal medicine or Chinese patent medicine with anti-tumor
indications within 2 weeks before the first dose.
4. received other investigational drugs or treatments within 4 weeks before the study
drug.
5. received systemic glucocorticoids (prednisone > 10 mg/ day or equivalent) or other
immunosuppressive agents within 14 days before the first dose of study drug; The use
of topical, ocular, intra-articular, nasal, and inhaled glucocorticoids was
excluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrast
allergy).
6. the adverse effects of previous antineoplastic therapy have not recovered to CTCAE
5.0 grade ≤1 or the relevant requirements of the inclusion criteria (except for
toxicities without safety risks judged by the investigators, such as alopecia, grade
2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement
therapy).
7. major surgical procedures (excluding needle biopsies) within 4 weeks before the
first dose of study drug, major trauma, or the need for elective surgery during the
trial.
8. prior allogeneic hematopoietic stem-cell transplantation or organ transplantation.
9. clinically symptomatic parenchymal or meningeal metastases.
10. have active infection and currently require intravenous anti-infective therapy.
11. have a history of immunodeficiency, including testing positive for human
immunodeficiency virus (HIV) antibodies.
12. active hepatitis B (HBsAg positive and HBV-DNA positive or greater than the upper
limit of normal), active hepatitis C (hepatitis C virus antibody positive and HCV
RNA positive or greater than the upper limit of normal).
13. received any live vaccine within 4 weeks before the first dose of study drug.
14. known hypersensitivity to any antibody-based drug (NCI CTCAE grade 5.0 ≥3) or to the
study drug, active ingredient, or inactive excipients of a PD-1/PD-L1 inhibitor.
15. with severe and uncontrollable lung diseases (severe infectious pneumonia,
interstitial lung disease, etc.); Or other moderate-to-severe lung diseases that
severely affect respiratory function that may interfere with the detection or
management of drug-related pulmonary toxicity.
16. have a history of severe cardiovascular and cerebrovascular disease, including but
not limited to:
① Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia
requiring clinical intervention, II-III degree atrioventricular block, etc.
② Mean QT interval corrected with Fridericia's method (QTcF) > 470 ms;
③ Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or
other grade 3 or above cardiovascular and cerebrovascular events occurred within 6
months before the first dose; ④ patients with New York Heart Association (NYHA)
functional class ≥II heart failure or left ventricular ejection fraction (LVEF) <
50% or structural heart disease with high risk as judged by other investigators; And
5) clinically uncontrolled hypertension.
17. have an active or previous autoimmune disease (e.g., systemic lupus erythematosus,
rheumatoid arthritis, vasculitis, etc.) with the possibility of recurrence, except
clinically stable autoimmune thyroid disease, type I diabetes mellitus, vitiligo,
cured atopic dermatitis in children, and psoriasis (within the past 2 years) that
does not require systemic treatment."
18. had other malignancies within 5 years before study administration, except for
malignancies that could be expected to be cured with treatment (including, but not
limited to, adequately treated thyroid cancer, carcinoma in situ of the cervix,
basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast
treated with radical surgery).
19. have clinically uncontrollable effusion in the third space, which was judged by the
investigator to be not suitable for enrollment.
20. known alcohol or drug dependence.
21. with mental disorders or poor adherence.
22. pregnant or lactating women.
23. The participant was deemed by the investigator to have a history of other serious
systemic diseases or to be ineligible for the study for other reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital Chinese Academy of Medical Sciences
Address:
City:
Beijing
Zip:
10021
Country:
China
Contact:
Last name:
YuanKai Shi, doctor
Phone:
8610-87788495
Email:
cancergcp@163.com
Start date:
October 1, 2024
Completion date:
August 1, 2029
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/NCT06581419
