IAH0968 in Combination With GC for the Treatment of HER2-Positive Unresectable Advanced/Metastatic Malignant Tumors

NCT05991518 | Recruiting Phase 1

• 1 other identifier: IAH0968-201
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to evaluate the efficacy and safety of IAH0968 in combination with gemcitabine and cisplatin for the treatment of HER2-positive unresectable advanced/metastatic malignant tumors and cholangiocarcinoma. The study is divided into two stages: Phase Ib, an open-label, non-randomized, multicenter dose-escalation trial, and Phase II, a randomized, double-blind, parallel-controlled, multicenter trial.

Conditions

HER2 Gene Mutation

Outcome Measures

Primary Outcomes (3)

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

  To investigate the safety characteristics.

  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

• Objective response rate (ORR) in dose expansion (Phase Ⅱa)

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

  Baseline through up to 1 years or until disease progression

Secondary Outcomes (25)

• Pharmacokinetic (PK) Cmax (Phase Ⅰ)

  Day1，2，3，4，6，8，11，14，17，21 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 Ⅰ)

  Day1，2，3，4，6，8，11，14，17，21 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 Ⅰ)

  Day1，2，3，4，6，8，11，14，17，21 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 Ⅰ)

  Day1，2，3，4，6，8，11，14，17，21 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 Ⅰ)

  Day1，2，3，4，6，8，11，14，17，21 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 Ia - Dose escalation

EXPERIMENTAL

To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and/or recommended phase II dose (RP2D) of intravenous IAH0968 in combination with the GC regimen for adult patients with HER2-positive advanced solid tumors who have failed standard treatment.

Combination Product: Injection of IAH0968+Gemcitabine+Cisplatin

Phase IIa - Clinical Exploratory Stage

EXPERIMENTAL

The RP2D determined from the Phase Ib study is used as the first-line treatment for HER2-positive advanced or metastatic biliary tract cancer (BTC) patients who have not received prior systemic therapy. The efficacy of IAH0968 in combination with the GC regimen is compared to the efficacy of placebo in combination with the GC regimen based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, using the objective remission rate (ORR) as the evaluation criteria.

Combination Product: Injection of IAH0968+Gemcitabine+Cisplatin; Combination Product: Gemcitabine+Cisplatin

Interventions

Injection of IAH0968+Gemcitabine+Cisplatin COMBINATION_PRODUCT

Administration of IAH0968 is given once per cycle, with each cycle defined as every 3 weeks.

Also known as: IAH0968+GC

Phase IIa - Clinical Exploratory Stage; Phase Ia - Dose escalation

Gemcitabine+Cisplatin COMBINATION_PRODUCT

Gemcitabine is administered at a dose of 1000 mg/m2 on the second day (D2) and ninth day (D9) of each cycle. At least 6 hours after the completion of gemcitabine infusion, cisplatin is administered at a dose of 70 mg/m2 on the second day (D2) of each cycle.

Also known as: GC

Phase IIa - Clinical Exploratory Stage

Eligibility Criteria

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

You may qualify if:

• Phase Ib
• The age of the participant should be 18 years or older.
• The participant should have been diagnosed with HER2-positive advanced solid tumors that have failed standard treatment, as confirmed by pathological histology or cytology. Standard treatment failure is defined as disease progression during or after the last treatment, or inability to tolerate treatment due to severe toxicity (grade ≥ 4 hematologic toxicity or grade ≥ 3 non-hematologic toxicity following previous standard treatment). HER2 positivity is defined as proven HER2-positive through immunohistochemistry (IHC) staining and/or fluorescence in situ hybridization (FISH). The interpretation and standards for HER2 positivity in breast cancer will follow current breast cancer guidelines, and for HER2 positivity in cancers other than breast cancer, current gastric cancer guidelines will be followed (Appendix 9).
• The GC regimen is the frontline standard treatment for the specific type of cancer (including urinary tract carcinoma, NSCLC, pancreatic cancer, nasopharyngeal carcinoma, etc.).
• The participant should have at least one measurable lesion according to RECIST 1.1 criteria, and the measurable lesion should not have undergone any local treatment (including local radiotherapy, ablation, and intervention therapy).
• The ECOG performance status should be 0 or 1 (refer to Appendix 3).
• During the screening phase, the participant's organ functions should be relatively normal (upper limit of normal values based on the respective study center's range), including:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Hemoglobin (Hgb) ≥ 90 g/L
• Platelet count (PLT) ≥ 90 × 109/L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 × upper limit of normal (ULN), or ≤ 5.0 × ULN for patients with liver metastasis
• Total bilirubin (TBIL) ≤ 1.5 × ULN
• Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min calculated according to the Cockcroft-Gault formula (refer to Appendix 2)
• All premenopausal women and women within 12 months of menopause should have a negative pregnancy test.
• Left ventricular ejection fraction (LVEF) ≥ 50%.

You may not qualify if:

• Phase Ib
• Known hypersensitivity reaction to any monoclonal antibody or a documented history of allergies to gemcitabine or cisplatin and its components.
• Previous treatment: (1) Not recovered from adverse reactions caused by previous anti-tumor treatment to normal levels (according to CTCAE 5.0, hematologic toxicity ≥ Grade 2, non-hematologic toxicity ≥ Grade 1), excluding radiation-induced late toxicities considered irreversible by the investigator such as alopecia and skin pigmentation. (2) Patients who have received treatment with trastuzumab/pertuzumab and their biosimilars (mono-therapy, combination chemotherapy, ADC drugs, bispecific antibodies, etc.) within 4 weeks prior to enrollment. (3) Patients who have participated in other clinical trials within 4 weeks prior to enrollment and have used investigational drugs during this period. (4) Patients who have previously received GC regimen treatment for anti-tumor therapy and experienced relapse due to drug resistance.
• Previous allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
• Surgical procedures within 4 weeks prior to enrollment, and the investigator considers that the patient's condition has not recovered to a level allowing for initiation of this study treatment (excluding previous diagnostic biopsies and biliary stent placement/percutaneous transhepatic cholangiographic drainage procedures performed to relieve bile duct obstruction \[PTBD\]).
• Vaccination with live vaccines within 4 weeks prior to enrollment, or receipt of blood transfusion within 2 weeks.
• Radiotherapy other than focal palliative bone radiotherapy within 4 weeks prior to enrollment.
• Clinical symptoms of central nervous system metastasis within 4 weeks prior to enrollment. Patients with previous treatment for brain or meningeal metastases may be included if the clinical condition is stable for at least 2 months and systemic steroid therapy (dose \> 10 mg/day prednisone or equivalent) has been discontinued for ≥ 4 weeks.
• Hospitalization or inability to undergo study treatment within 30 days prior to randomization due to exacerbation of chronic obstructive pulmonary disease or other respiratory diseases.
• Liver transplant candidates and patients who can undergo transplantation during a medically acceptable period.
• Presence of severe or poorly controlled diseases, including but not limited to: (1) myocardial infarction, clinically significant arrhythmias requiring treatment, congestive heart failure, myocarditis, and angina pectoris occurring within 6 months prior to enrollment. (2) Hepatitis B virus (HBV) infection with positive HBV DNA (≥1.0×104 copies/mL or ≥2000 IU/mL), hepatitis C virus (HCV) infection with positive HCV RNA (\>1.0×103 copies/mL or \>100 IU/mL), and positive human immunodeficiency virus (HIV) test. (3) Active tuberculosis (clinical symptoms, physical examination findings, or radiographic evidence of active tuberculosis). (4) Severe and uncontrolled pulmonary diseases (severe infectious pneumonia, interstitial lung disease, etc.) (≥ Grade 3 CTCAE). (5) Uncontrolled biliary infection. Biliary obstruction should be relieved by endoscopic or percutaneous transhepatic biliary drainage (PTBD). Patients with biliary obstruction should have sufficient biliary drainage and no evidence of ongoing infection at the time of enrollment and on Day 1 of Cycle 1 without antibiotic treatment. (6) Severe infections of any type that are uncontrolled (≥ Grade 3 CTCAE). (7) Presence of ascites, pleural effusion, or pericardial effusion requiring drainage before the first study drug treatment.
• Presence of other conditions considered inappropriate for participation in this study by the investigator.
• Phase IIa
• Known hypersensitivity reaction to any monoclonal antibody.
• History of allergy to gemcitabine or cisplatin and its components.

Sponsors & Collaborators

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

Study Sites (1)

Fudan University Affiliated Zhongshan Hospital

Shanghai, China

RECRUITING

Study Officials

• Zhou Jian, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

• Liu Tianshu, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

cao jianxiang, M.D.

CONTACT

18018039840; caojianxiang@sunho-bio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 14, 2023
• Study Start: April 25, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

CN (1)