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

SUNHO（China）BioPharmaceutical CO., Ltd.1 site in 1 country50 target enrollmentMarch 1, 2024

ConditionsAdvanced Malignant Tumors

InterventionsIAP0971

DrugsIAP0971

Overview

Phase: Phase 1
Intervention: IAP0971
Conditions: Advanced Malignant Tumors
Sponsor: SUNHO（China）BioPharmaceutical CO., Ltd.
Enrollment: 50
Locations: 1
Primary Endpoint: Dose limiting toxicities (DLTs) (Phase Ib)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

March 1, 2024

End Date

March 1, 2027

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

SUNHO（China）BioPharmaceutical CO., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age 18 to 75years, male or female.
•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.
•At least one measurable tumor lesion per RECIST 1.1 (solid tumors).
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
•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.
•Expected survival time of more than 3 months.
•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.

Exclusion Criteria

•1.Phase II: Pathohistologically confirmed with small cell lung cancer components, or sarcomatoid lesions.
•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.
•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.
•Receipt of other non-marketed investigational drugs or treatments within 4 weeks before the first administration.
•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).
•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.
•Brain parenchymal metastasis or meningeal metastasis with clinical symptoms.
•active infection and currently needs intravenous anti-infection treatment.

Arms & Interventions

Phase Ib - Dose escalation

Intervention: IAP0971

Phase II - Clinical Exploratory Stage

Intervention: IAP0971

Outcomes

Primary Outcomes

Dose limiting toxicities (DLTs) (Phase Ib)

Time Frame: 21 days after first dose

To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D).

Frequency of adverse events (AEs) and SAEs (Phase Ib)

Time Frame: 3 months after end event visit

To investigate the safety characteristics.

PFS in dose expansion (Phase II)

Time Frame: Baseline through up to 2 years or until disease progression

To explore the clinical effectiveness. Tumor response based on RECIST 1.1.

Secondary Outcomes

Pharmacokinetic (PK) R(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(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)(Baseline through up to 2 years or until disease progression)
Incidence of adverse events (AEs) and SAEs (Phase Ib)(3 months after end event visit)
Overall survival (OS) (Phase II)(Baseline through up to 2 years or until disease progression)
Immunogenicity of IAH0968 (Phase II)(3 months after end event visit)
Pharmacokinetic (PK) Vd (Phase Ib)(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)(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(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(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(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)
Immunogenicity of IAH0968 (Phase Ib)(3 months after end event visit)
ORR (Phase Ⅱ)(Baseline through up to 2 years or until disease progression)
Pharmacokinetic (PK) AUCss(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(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)
Disease control rate (DCR) (Phase II)(Baseline through up to 2 years or until disease progression)
Incidence of adverse events (AEs) and SAEs (Phase II)(3 months after end event visit)
Pharmacokinetic (PK) Cmax (Phase Ib)(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)(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)(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)(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(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)(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)(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)