A Clinical Trial to Evaluate Effect of IAP0971 in Patients With Advanced Malignant Tumors

A Clinical Trial of Phase Ib/II to Evaluate Effect of IAP0971 in Patients With Advanced Malignant Tumors

This is a Phase Ib/II Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of IAP0971 in Patients with Advanced Malignant Tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Tumors
• Intervention / Treatment: Drug: IAP0971

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Kai Yuan Shi, doctor; Phone Number: 8610-87788495; Email: cancergcp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age 18 to 75years, male or female.
• 2. Phase Ib:With advanced or metastatic malignant solid tumor confirmed by histopathology, the standard treatment fails, or there is no standard treatment plan, or standard treatment is not applicable at this stage, or the patient refuses the standard treatment, or the investigator evaluates the patient who can benefit from this treatment.
• 3.Phae II: Confirmed by histopathology that it is not feasible to perform complete resection and cannot be connected. Locally advanced (stage IIIB or IIIC) or metastatic (IV) after radical concurrent radiotherapy and chemotherapy Stage) non-small cell lung cancer (NSCLC). Note: For unacceptable radical synchronization/sequencing.Subjects with locally advanced stage IIIB/IIIC of radiotherapy and chemotherapy need to be evaluated by relevant professional doctors. And provide written records to confirm.
• 4.Phae II: Never received systemic anti-tumor therapy for locally advanced or metastatic NSCLC before. Tumor treatment(received adjuvant/neoadjuvant chemotherapy or radical treatment for locally advanced diseases) .Patients with synchronous or sequential radiotherapy and chemotherapy and disease progression occurred after the last treatment ≥6 months).
• 5.Phase II: PD-L1 was positive (TPS≥50%) by IHC, and the patient was immunohistochemical. Epidermal growth factor receptor (EGFR) and anaplasticlymphomakinase (ALK) were negative.
• 6. At least one measurable tumor lesion per RECIST 1.1 (solid tumors).
• 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 7. The estimated survival time is ≥3 months.8.Adequate organ function: Hematological system (No blood transfusion or hematopoietic stimulating factor therapy within 14 days) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L White blood cell count (WBC) ≥ 3.0 × 109/L Platelets (PLT) ≥ 75 × 109/L Hemoglobin (Hb) ≥ 90 g/L Hepatic function Total bilirubin (TBIL) ≤ 3 × ULN Alanine aminotransferase (ALT) ≤ 3 × ULN; Aspartate aminotransferase (AST) ≤ 3 × ULN; Renal function Creatinine clearance (Ccr) (only calculated if creatinine > 3 × ULN) ≥ 50 mL/min (calculated according to Cockcroft-Gault formula, see Appendix 7 for formula) Coagulation function Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN International normalized ratio (INR) ≤ 1.5 × ULN.
• 8. Expected survival time of more than 3 months.
• 9. Eligible patients of childbearing potential (men and women) must agree to use a reliable method of contraception (hormonal or barrier method or abstinence, etc.) with their partners during the trial and for at least 90 days after study drug administration; female patients of childbearing potential (see Appendix 8 for definition) must have a negative blood or urine pregnancy test 7 days before the first administration.
• 10. Eligible patients with fertility (male and female) must agree that during and at the end of the trial.Use reliable contraceptive methods (hormones or screens) with their partners for at least 6 months after taking the drug.Obstacle law or abstinence); Blood of female patients of childbearing age within 7 days before the first use of the study drug.The pregnancy test must be negative.
• 11.Subjects must be informed of the study prior to the trial and voluntarily sign a written informed consent form.

Exclusion Criteria:

• 1.Phase II: Pathohistologically confirmed with small cell lung cancer components, or sarcomatoid lesions.
• 2. Phase II : Previous immunotherapy, including immune checkpoint inhibitors (such as PD-1/PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonist (such as:ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immune cell therapy, etc.
• 3. Phase Ib: Patients who received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, and other anti-tumor treatment within 4 weeks before the first administration, except for the following: Nitrosourea or mitomycin C was received within 6 weeks before the first administration; Oral fluoropyrimidines and small molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to the first administration.Chinese proprietary medicines with anti-tumor indications were received within 2 weeks before the first administration.
• 4. Receipt of other non-marketed investigational drugs or treatments within 4 weeks before the first administration.
• 5. Patients who have received systemic glucocorticoids (prednisone > 10 mg/day or equivalent doses of similar drugs) or other immunosuppressive agents within 14 days before the first administration; exclude the following conditions: topical, ophthalmic, intra-articular, intranasal or inhaled corticosteroid therapy; short-term use of glucocorticoid for preventive treatment (for example, prevention of contrast agent allergy).
• 6.The adverse reactions of previous anti-tumor treatments have not recovered to CTCAE 5.0 grade evaluation ≤1 grade.Or the relevant provisions of the selection criteria (except for the toxicity that the researcher judges to have no safety risk).
• 7. Patients who have undergone major organ surgery (excluding needle biopsy) or have significant trauma within 4 weeks before the first administration, or require elective surgery during the trial.
• 8.Previously received allogeneic hematopoietic stem cell transplantation or organ transplantation.
• 9. Brain parenchymal metastasis or meningeal metastasis with clinical symptoms.
• 10. active infection and currently needs intravenous anti-infection treatment.
• 11. immunodeficiency disease, including HIV antibody positive.
• 12. Active hepatitis B (HBsAg positive and HBV-DNA positive or above normal) Limit), active hepatitis C (hepatitis C virus antibody positive and HCV RNA positive Or greater than the upper limit of normal value).
• 13.Vaccinated with any live vaccine within 4 weeks before the first use of the study drug.
• 14. Hypersensitivity to any antibody drugs (NCI CTCAE 5.0 grade evaluation ≥3 Grade), or active ingredients or inactive excipients of research drugs and PD-1/PD-L1 inhibitors.
• 15.With serious and uncontrollable lung diseases (severe infectious pneumonia, interstitial lung disease Etc.); Or other serious effects that may interfere with the detection or treatment of drug-related pulmonary toxicity. Moderate and severe lung diseases with respiratory function.
• 16. History of serious cardiovascular and cerebrovascular diseases, including but not limited to: Patients with severe cardiac rhythm or conduction abnormalities, such as arrhythmia requiring clinical intervention, second-degree to third-degree atrioventricular block; QT interval (QTcF) corrected by Fridericia's method > 470 ms (see Appendix 9 for calculation formula); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 and above cardiovascular and cerebrovascular events within 6 months prior to the first dose; Patients with heart failure with cardiac function class ≥ II according to New York Heart Association (NYHA) (see Appendix 4) or Left Ventricular Ejection Fraction (LVEF) < 50%; Clinically uncontrolled hypertension.
• 17. Patients who currently have active or have had autoimmune diseases that may have recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroid diseases, type I Diabetics.
• 18. Suffering from other malignant tumors within 5 years before the start of drug administration, except for the following cases: Malignant tumor that can be expected to be cured after treatment (including but not limited to fully treated thyroid gland) cervical carcinoma in situ, basal or squamous cell skin cancer or breast treated by radical surgery. Ductal carcinoma in situ, etc.).
• 19. Clinically uncontrolled effusion in the third space, which is not suitable for enrollment based on the investigator's judgment.
• 20. Known alcohol or drug dependence.
• 21. Patients with mental disorders or poor compliance.
• 22. Women who are pregnant or breastfeeding.
• 23. The subject has a history of other serious systemic diseases or other reasons that make the subject unsuitable for this clinical study in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ib - Dose escalation	Drug: IAP0971; IAP0971 should be subcutaneous injected，q3w
Experimental: Phase II - Clinical Exploratory Stage	Drug: IAP0971; IAP0971 should be subcutaneous injected，q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events (AEs) and SAEs (Phase Ib)	To investigate the safety characteristics.	3 months after end event visit
Dose limiting toxicities (DLTs) (Phase Ib)	To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D).	21 days after first dose
PFS in dose expansion (Phase II)	To explore the clinical effectiveness. Tumor response based on RECIST 1.1.	Baseline through up to 2 years or until disease progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Cmax (Phase Ib)	PK parameters (Cmax) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) Cmin (Phase Ib)	PK parameters (Cmin) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) Tmax (Phase Ib)	PK parameters (Tmax) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) AUC 0-t (Phase Ib)	PK parameters (AUC 0-t) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) AUC 0-∞ (Phase Ib)	PK parameters (AUC 0-∞) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) Vd (Phase Ib)	PK parameters (Vd) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) t1/2 (Phase Ib)	PK parameters (t1/2) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) λz (Phase Ib)	PK parameters (λz) following single dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) Css,max	PK parameters (Css,max) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) Css,min	PK parameters (Css,min) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) Css,av	PK parameters (Css,av) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) AUCss	PK parameters (AUCss) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) CKss	PK parameters (CLss) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK）Vss	PK parameters (Vss) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) R	PK parameters (R) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Pharmacokinetic (PK) DF	PK parameters (DF) following multiple dose.	Day1，2，3，4，6，7，11，14，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years
Objective response rate (ORR) in dose escalation (Phase Ib)	Tumor response based on RECIST 1.1.	Baseline through up to 2 years or until disease progression
Incidence of adverse events (AEs) and SAEs (Phase Ib)	To investigate the safety characteristics.	3 months after end event visit
Immunogenicity of IAH0968 (Phase Ib)	The frequency of anti-drug antibodies (ADA) against IAP0971.(Phase Ib)	3 months after end event visit
ORR (Phase Ⅱ)	ORR as assessed using RECIST 1.1.	Baseline through up to 2 years or until disease progression
Overall survival (OS) (Phase II)	OS as assessed using RECIST 1.1.	Baseline through up to 2 years or until disease progression
Disease control rate (DCR) (Phase II)	DCR as assessed using RECIST 1.1.	Baseline through up to 2 years or until disease progression
Incidence of adverse events (AEs) and SAEs (Phase II)	To investigate the safety characteristics.	3 months after end event visit
Immunogenicity of IAH0968 (Phase II)	The frequency of anti-drug antibodies (ADA) against IAP0971.(Phase II)	3 months after end event visit

Collaborators and Investigators

• Sponsor: SUNHO（China）BioPharmaceutical CO., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 18, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: IAP0971-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: we donot share.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No