Safety of GQ1001 in Adult Patients With HER2-Positive Advanced Solid Tumors

NCT04450732 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: GQ1001X2101
• Study Type: interventional
• Target: 96
• Locations: 3 countries
• Sites: 24

Brief Summary

Phase I Dose Finding Study for GQ1001 in Patients with HER2-Positive Advanced Solid Tumors

Conditions

HER2-positive Breast Cancer; HER2-positive Biliary Tract Cancer; HER2-Positive Salivary Gland Carcinomas; HER2-Positive Advanced Solid Tumor

Keywords

HER2-positive; Biliary Tract Cancer; Salivary Gland Carcinomas; Non- Small Cell Lung Cancer; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLTs).

  Adverse events will be assessed using NCI CTCAE version 5.0 and will be evaluated by the investigator and the sponsor for the eligibility of DLT.

  End of Cycle 1 (21-day cycle)

• Maximum Tolerated Dose (MTD) or Dose Recommended for Dose Expansion (DRDE)

  The SRC will also determine the MTD/DRDE based on the totality of data for all tested dose levels.

  After each cohort completes the DLT observation period (Day 1 to Day 21 after the first dose of study treatment) or has a DLT or becomes not DLT-evaluable

Secondary Outcomes (14)

• Incidence and Severity of Adverse Events (AEs)

  from baseline to 30 days after last dose

• Number of Participants with Abnormal Laboratory Values

  rom baseline through Cycle 8 (each cycle is 21 days) and up to 30 days from treatment discontinuationafter last dose

• Area Under the Plasma Concentration Versus Time Curve (AUC) of GQ1001

  through study completion, an average of 1 year

• Peak Plasma Concentration of GQ1001 (Cmax)

  through study completion, an average of 1 year

• Time at which the Cmax is Observed (Tmax)

  through study completion, an average of 1 year

Study Arms (2)

Dose Escalation

EXPERIMENTAL

GQ1001 will be administered intravenously every 21 days. Dose Escalation will be guided by a modified 3+3 design.

Drug: GQ1001

Dose Expansion

EXPERIMENTAL

GQ1001 at the Dose Recommended for Dose Expansion will be administered intravenously every 21 days. Dose expansion will further evaluate the MTD or DRDE in different types of malignant solid tumor in four cohorts.

Drug: GQ1001

Interventions

GQ1001 DRUG

anti-HER2 antibody drug conjugate

Dose Escalation; Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form and able to comply with the protocol;
• Male and female subjects ≥18 years of age;
• ECOG PS of 0 or 1, the estimated life expectancy ≥ 3 months;
• LVEF ≥ 50% as determined by echocardiography (ECHO);
• Patients must have pathologically documented advanced/unresectable or metastatic solid tumor with HER2-positive (as defined below) that is relapsed or refractory to standard therapy or for which there is no standard therapy and progressed. Patients must have a least one measurable disease lesion. Tumor specimens to identify HER2 status should be obtained within the past 6 months.
• Definition of HER2-positive
• Advanced/unresectable or metastatic breast cancer: immunohistochemistry (IHC) 3+, or IHC 2+ and in situ hybridization positive (ISH+)\*;
• Advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: IHC 3+, or IHC 2+ and ISH+\*;
• Other HER2-positive advanced/unresectable or metastatic solid malignant tumor: determined by IHC, ISH, Next Generation Sequencing, or other analysis techniques as appropriate;
• ISH: fluorescence in situ hybridization (FISH) or dual in situ hybridization (DISH); ISH positivity is defined as a ratio of ≥ 2.0 for the number of HER2 gene copies to the number of signals for CEP17. ISH assay is not required when IHC result is 3+. ISH assay should be performed to confirm HER2 positivity when IHC result is 2+.
• Adequate organ function confirmed at screening and within 7 days before the first treatment, as evidenced by:
• Platelet count: ≥ 100,000/mm3 ; Hemoglobin : ≥ 9 g/dL; Absolute neutrophil count (ANC): ≥ 1500/mm3 ; Serum creatinine: ≤ 1.5 × ULN (upper limit of normal), or creatinine clearance ≥ 60 mL/min (using Cockcroft Gault formula) ; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) : ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present); Total bilirubin : ≤ 1.5 × ULN (except for patients with Gilbert's Syndrome); Prothrombin time and activated partial thromboplastin time: ≤ 1.5 × ULN.
• Adequate washout period before the first treatment as defined by:
• Major surgery: ≥ 4 weeks. Radiation therapy: ≥ 4 weeks (≥ 2 weeks for palliative stereotactic radiation therapy without abdominal). Autologous transplantation: ≥ 3 months.
• Hormonal therapy: ≥ 2 weeks or per Investigator's discretion for breast cancer patients.

You may not qualify if:

• Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of chemotherapy or radiotherapy;
• Subjects with multiple primary malignancies within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral breast cancer);
• Cardiovascular dysfunction or clinically significant cardiac disease, including but not limited to:
• Medical history of symptomatic chronic heart failure (New York Heart Association (NYHA) classes II-IV) or serious cardiac arrhythmia requiring treatment;
• Medical history of myocardial infarction or unstable angina within 6 months of the first treatment;
• Corrected QT interval by Fridericia (QTcF) prolongation of \> 450 milliseconds (ms) in males and \> 470 ms in females;
• Medical history of clinically significant lung disease (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis), or patients who are suspected to have these diseases by imaging at screening or requirement for supplemental oxygen;
• Known hypersensitivity to either the drug substances or inactive ingredients in the drug product;
• Existing Grade ≥ 2 peripheral neuropathy;
• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE version 5.0, Grade ≤ 1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator;
• Cumulative anthracycline dose \> 360 mg/m2 doxorubicin or equivalent;
• Uncontrolled infection requiring i.v. of antibiotics, antivirals or antifungals;
• Active infection with hepatitis C (e.g., detectable antibodies to hepatitis C virus \[HCV\]) or hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] positive) except subjects with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening, and these subjects must be willing to undergo monthly DNA testing and appropriate antiviral therapy as indicated;
• Patients with a history or current evidence of any concomitant condition, therapy, or laboratory abnormality that, in the opinion of the Investigator, might confound the results of the trial, interfere with the patient's participation and compliance;
• Women who are lactating or pregnant, as confirmed by pregnancy test within 7 days before first treatment;

Sponsors & Collaborators

• GeneQuantum Healthcare (Suzhou) Co., Ltd.: lead

Study Sites (24)

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

COMPLETED

Scientia Clinical Research Limited

Randwick, New South Wales, 2031, Australia

RECRUITING

Cabrini Institute in Melbourne, Australia

Melbourne, Victoria, 3050, Australia

COMPLETED

The first affiliated hospital of Bengbu medical college

Bengbu, Anhui, 233099, China

RECRUITING

Beijing Tongren Hospital Affiliated to Capital University of Medical Sciences

Beijing, Beijing Municipality, 100005, China

RECRUITING

Chinese PLA general hospital

Beijing, Beijing Municipality, 100039, China

RECRUITING

Southern Medical University Hospital in the south

Guangzhou, Guangdong, 516006, China

RECRUITING

Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, 528406, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

Hubei Huazhong University of Science and provincial Cancer Hospital Affiliated Union Hospital of Tongji Medical College

Wuhan, Hubei, 430022, China

RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410029, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110801, China

RECRUITING

Shandong Tumor Hospital

Jinan, Shandong, 250117, China

RECRUITING

Shanghai Ninth People's Hospital affiliated with the Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Ruijin Hospital, Affiliated to Shanghai Jiaotong University

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Changhai Hospital of Shanghai

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

West China School of Medicine and West China Hospital, Sichuan University

Chengdu, Sichuan, 610044, China

RECRUITING

First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310005, China

RECRUITING

Related Publications (1)

• Zhou C, Wang B, Teng C, Yang H, Piha-Paul SA, Richardson G, Malalasekera A, Sun Y, Wang W, Liu J, Shi Y, Zhan X, Lemech C. A phase Ia study of a novel anti-HER2 antibody-drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors. J Transl Med. 2025 Jan 9;23(1):37. doi: 10.1186/s12967-024-05985-z.

  PMID: 39789619 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Yan Shi

CONTACT

0512-66526166; shiy@genequantum.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

Model Details: Modified 3+3 Design

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 29, 2020
• Study Start: July 7, 2020
• Primary Completion: March 1, 2024
• Study Completion: May 1, 2024
• Last Updated: December 5, 2023

Record last verified: 2023-11

Locations

AU (2); CN (21); US (1)