To Evaluate IAH0968 in Combination With CAPEOX in HER2-positive Gastric Cancer

NCT06504732 | Recruiting Phase 2

• 1 other identifier: IAH0968-203
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The safety, tolerability, and determination of the maximum tolerated dose (MTD) of the combination therapy were first evaluated for IAH0968 in combination with or without the CAPEOX regimen in unsystematically treated subjects with HER2-expressing advanced/metastatic colorectal or gastric cancers (including adenocarcinomas of the gastro-esophageal junction) or HER2-hypo-expressing advanced/metastatic solid tumors. The efficacy of IAH0968 in combination with the CAPEOX regimen versus trastuzumab in combination with the CAPEOX regimen in subjects with HER2-positive advanced/metastatic gastric cancer, including gastro-esophageal junction adenocarcinoma, was then assessed by progression-free survival (PFS) according to the Research and Evaluation Criteria for the Evaluation of Efficacy in Solid Tumors (RECIST) 1.1.

Conditions

Stomach Neoplasms; Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced At Least One Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.

  Up to approximately 48 months

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

  Up to approximately 48 months

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  PFS was defined as the time from randomization to the first documented 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.

  Up to approximately 48 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

10-20 subjects with HER2-positive advanced/metastatic gastric cancer (including adenocarcinoma of the gastro-esophageal junction) without systemic treatment will be enrolled in combination with the CAPEOX regimen at a dose of 15 mg/kg of IAH0968 to assess the safety and tolerability of the combination therapy.

Drug: IAH0968

Cohort 2

EXPERIMENTAL

10-30 subjects with advanced/metastatic malignant solid tumors with low HER2 expression who have failed standard therapy or have no standard therapy will be enrolled at the 20 mg/kg IAH0968 dose to assess the safety and tolerability of IAH0968 monotherapy. The safety of IAH0968 at 15 mg/kg in combination with the CAPEOX regimen will be evaluated if the starting dose group, i.e., exceeds the MTD.

Drug: IAH0968

Cohort 3

EXPERIMENTAL

The CAPEOX regimen will be combined at the 20 mg/kg IAH0968 dose to enroll 20-40 unsystematically treated subjects with advanced/metastatic colorectal or gastric cancers with low expression of HER2, including adenocarcinomas of the gastro-esophageal junction, in order to assess the safety and tolerance of the combination therapy. The safety of IAH0968 at 15 mg/kg in combination with the CAPEOX regimen will be evaluated if the starting dose group, i.e., exceeds the MTD.

Drug: IAH0968

Interventions

IAH0968 DRUG

Subjects were treated with IAH0968 in combination with or without the CAPEOX regimen in the corresponding groups. Every 3 weeks was defined as a treatment cycle and IAH0968 was used for a maximum of 35 cycles.

Cohort 1; Cohort 2; Cohort 3

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 18\~75 years old (including critical mass), gender is not limited. 2) Phase II cohort 1 and III only: patients with locally advanced or metastatic gastric cancer (including adenocarcinoma of the gastro-esophageal junction) diagnosed by histopathology, unsuitable for radical surgical resection or localized treatment, and who have not received systemic antitumor therapy (including systemic chemotherapy, molecularly-targeted drug therapy, biologic therapy, and other investigational therapeutic agents) for GC (except for adjuvant chemotherapy for \>6 months), and who have demonstrated disease progression; and patients who have been diagnosed by immunohistochemistry (IHC) staining and/or fluorescence in situ hybridization (FISH). and demonstrated disease progression excepted); HER2 positivity (IHC 3+, or IHC 2+ and FISH +) demonstrated by immunohistochemical (IHC) staining and/or fluorescence in situ hybridization (FISH).
• \) Phase II Cohort 2 only: Have histologically or cytologically confirmed advanced malignant solid tumors that have failed standard treatment, or for which no standard treatment options are available, or for which standard treatment is not applicable at this stage; and are HER2 underexpressed (IHC 2+ and FISH-, or IHC 1+) as evidenced by immunohistochemistry (IHC) staining and/or fluorescence in situ hybridization (FISH).
• \) Phase II Cohort 3 only: with locally advanced or metastatic gastric cancer (including gastro-oesophageal junction adenocarcinoma) or colorectal cancer diagnosed by histopathology, unsuitable for radical surgical resection or localized treatment, with no prior systemic (including systemic chemotherapy, molecularly-targeted drug therapy, biologic therapy, and other investigational therapeutic agents) antitumor therapy (having received adjuvant chemotherapy for \>6 months with evidence of disease progression), patients with wild-type KRAS, NRAS, and BRAF genes (mCRC only); and HER2 low expression (IHC 2+ and FISH-, or IHC 1+) demonstrated by immunohistochemical (IHC) staining and/or fluorescence in situ hybridization (FISH).
• \) At least 1 measurable lesion according to RECIST 1.1 criteria (tumor lesions located in the area of prior radiotherapy or other localized regional treatment sites are generally not considered measurable lesions unless the lesion shows definite progression or persists after three months of radiotherapy).
• \) Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1. 7) Have an expected survival of ≥ 3 months. 8) Adequate organ function:
• Hematologic system (no transfusion or hematopoietic stimulating factor therapy within 14 days): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 90 × 109/L, hemoglobin (HGB) ≥ 90 g/L; Liver function: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN), except Gilbert's syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 times the ULN, liver metastasis or hepatocellular carcinoma patients need to AST and ALT ≤ 5.0 times the ULN and total bilirubin ≤ 3.0 times the ULN; Renal function: serum creatinine (Cr) ≤1.5 times ULN; if creatinine \>1.5 times ULN, creatinine clearance (Ccr) ≥50 mL/min (calculated according to Cockcroft-Gault formula);
• ④ Coagulation function: International Normalized Ratio (INR) ≤ 1.5 times ULN for prothrombinogen, Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN, or INR and APTT ≤ 2.5 times ULN for patients with liver metastasis or hepatocellular carcinoma.
• \) Eligible patients (male and female) of childbearing potential must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) with their partner for the duration of the trial and for at least 6 months after the last dose; female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study drug.
• \) Subjects must give informed consent for this study prior to the trial and voluntarily sign a written informed consent form.

You may not qualify if:

• \) Phase II Cohort 2 only: received antitumor therapy such as chemotherapy, radiotherapy, biologic therapy, endocrine therapy, immunotherapy, etc. within 4 weeks prior to the first use of study drug, except for the following:
• Nitrosourea or mitomycin C within 6 weeks prior to first use of study drug;
• ② Oral fluorouracil analogs and small molecule targeted drugs for 2 weeks prior to the first use of the study drug or within 5 half-lives of the drug (whichever is longer);
• ③ Within 2 weeks prior to first use of the study drug for proprietary Chinese medicines with antitumor indications.
• \) Received other unlisted clinical investigational drug or therapy within 4 weeks prior to first use of the study drug.
• \) Adverse effects of prior antineoplastic therapy have not returned to NCI CTCAE 5.0 grade rating of ≤ grade 1 or relevant provisions of the enrollment criteria (except for toxicities judged by the investigator to pose no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacement therapy).
• \) Known hypersensitivity to any antibody-based drug (NCI CTCAE 5.0 grade rating ≥ 3) or hypersensitivity to the study drug and the active ingredient or inactive excipients of the CAPEOX regimen.
• \) Diagnosed defective mismatch repair (dMMR) or high microsatellite instability (MSI-H) solid tumor (except unknown MSI/MMR status).
• \) Major surgical procedure (excluding puncture biopsy), major trauma within 4 weeks prior to first use of study drug, or need for elective surgery during the trial.
• \) Received systemic glucocorticosteroids (prednisone \> 10 mg/day or equivalent) within 14 days prior to the first dose of study drug, except for the following: treatment with topical, ocular, intra-articular, intranasal, and inhaled glucocorticosteroids; and short-term prophylactic glucocorticosteroids (e.g., for prevention of allergy to contrast media).
• \) Other immunosuppressive therapy within 28 days or 5 half-lives (whichever is longer) prior to first use of study drug.
• \) Use of immunomodulatory drugs within 14 days prior to first use of study drug.
• \) Use of any live vaccine within 4 weeks prior to the first dose of study drug.
• \) Previous allogeneic hematopoietic stem cell transplantation or organ transplantation.
• \) Parenchymal brain metastases or meningeal metastases with clinical symptoms.

Sponsors & Collaborators

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

Study Sites (2)

The First Hospital of China Medical University

Shenyang, Liaoning, 637000, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Zhenning Wang, PhD

CONTACT

13998891377; JOSIEON826@sina.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 17, 2024
• Study Start: August 15, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028
• Last Updated: January 20, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)