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

NCT06581419 | Recruiting Phase 1

• 1 other identifier: IAP0971-203
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Malignant Neoplasm; Advanced or Metastatic Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Frequency of adverse events (AEs) and SAEs (Phase I)

  To investigate the safety characteristics.progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data.

  3 months after end event visit

• Dose limiting toxicities (DLTs) (Phase I)

  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 Outcomes (23)

• pharmacokinetic parameters Cmax (Phase I)

  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 parameters Tmax (Phase I)

  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 parameters AUC 0-t (Phase I)

  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 parameters AUC 0-∞ (Phase I)

  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 parameters CL (Phase I)

  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

Study Arms (2)

phase I

EXPERIMENTAL

Dose escalation (Phase I): 14 to 48 subjects with advanced malignancies are planned to be enrolled to initially investigate the safety and tolerability of IAP0971 and to determine the MTD based on the frequency of DLT in each dose arm.The starting dose of IAP0971 for injection is 0.0005 mg/kg, with a preset maximum escalation dose of 18.0 mg/kg, administered once every 3 weeks.

Drug: IAP0971

phase II

EXPERIMENTAL

Dose Extension (Phase II) : Phase II will use an open-label, non-randomized, single-arm, multicenter design. Under the RP2D dose determined in Phase I, 20-30 untreated patients with advanced or metastatic non-small cell lung cancer, who are driver gene negative and PD-L1 positive (TPS ≥ 50%), will be enrolled. The drug IAP0971 is administered once every 3 weeks, and every 3 weeks is 1 cycle

Drug: IAP0971

Interventions

IAP0971 DRUG

Subjects receive IAP0971, which will be administered every 3 weeks in a 3-week cycle.

phase I; phase II

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-75 years old (including cut-off value), regardless of gender.
• 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.
• 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.
• 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).
• 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.
• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• predicted survival time ≥3 months.
• 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.
• 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.
• Subjects must give informed consent for this study and voluntarily provide written informed consent before the trial.

You may not qualify if:

• Phase II only: small cell lung cancer or sarcomatoid lesion confirmed by histopathology.
• 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.
• 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.
• received other investigational drugs or treatments within 4 weeks before the study drug.
• 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).
• 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.
• prior allogeneic hematopoietic stem-cell transplantation or organ transplantation.
• clinically symptomatic parenchymal or meningeal metastases.
• have active infection and currently require intravenous anti-infective therapy.
• have a history of immunodeficiency, including testing positive for human immunodeficiency virus (HIV) antibodies.
• 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).
• received any live vaccine within 4 weeks before the first dose of study drug.

Sponsors & Collaborators

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

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 10021, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

YuanKai Shi, doctor

CONTACT

8610-87788495; cancergcp@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: September 3, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)