A Study of GQ1005 in Subjects With HER2-Expressing Advanced Solid Tumors

NCT ID: NCT06154343

Last Updated: 2023-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-23

Study Completion Date

2025-07-30

Brief Summary

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This is an open-label, phase I study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of GQ1005 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects.

Detailed Description

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Conditions

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HER2 Expressing or Mutated Advanced Malignant Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation

GQ1005 will be administered intravenously every 21 days. Dose Escalation will be guided by Bayesian Optimal Interval (BOIN) Design.

Multiple dose grouping

Group Type EXPERIMENTAL

GQ1005

Intervention Type DRUG

an antibody drug conjugate

Dose Expansion

GQ1005 at the recommended phase II dose (RP2D) will be administered intravenously every 21 days. Dose expansion will further evaluate the MTD or RP2D in different types of malignant solid tumor in four cohorts.

Group Type EXPERIMENTAL

GQ1005

Intervention Type DRUG

an antibody drug conjugate

Interventions

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GQ1005

an antibody drug conjugate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Voluntary agreement to provide written informed consent;
2. Aged 18 years or older, both male and female.
3. The expected survival time is more than 3 months.
4. ECOG performance status Score 0 or 1.
5. LVEF ≥ 50% by ECHO or MUGA scan within 28 days prior to the first dose of study drug.
6. Histologically or cytologically confirmed malignancy with at least 1 measurable lesion as assessed by RECIST v1.1.
7. Good organ function, confirmed by the following laboratory test results at Screening and within 7 days prior to the first dose of study drug:

Platelet count ≥ 100,000/mm3; hemoglobin ≥ 9g/dL; ANC ≥ 1500/mm3; Serum CREA ≤ 1.5 × ULN, or estimated CREA clearance ≥ 60 mL/min (Cockcroft-Gault equation); ALT and AST ≤ 3 × ULN (≤ 5 x ULN if liver metastases are present); Total bilirubin ≤ 1.5 x ULN for subjects with Gilbert's syndrome or ≤ 2 x ULN for subjects with liver metastases at baseline; Prothrombin time and activated partial thromboplastin time ≤ 1.5 × ULN;
8. Adequate washout period prior to the first treatment, defined as follows:

Major surgery ≥ 4 weeks; radiotherapy ≥ 4 weeks (≥ 2 weeks if the radiotherapy is palliative stereotactic radiotherapy without abdominal involvement); seed-radioactive therapy ≥ 3 months; Nuclein therapy ≥ 3 months; autotransplantation ≥ 3 months; Hormone therapy ≥ 2 weeks or as per investigator's judgment (breast cancer subjects) Chemotherapy or targeted therapy (including antibody drug therapy) ≥ 2 weeks (5-FU-based drugs, folinic acid preparations and/or weekly paclitaxel therapy);
* 2 weeks (or 5 half-lives, whichever is longer) (tyrosine kinase inhibitor);
* 4 weeks (HER2-targeted biological therapy);
* 6 weeks (nitrosourea or mitomycin C);
* 3 weeks (any other chemotherapy/targeted therapy);
* 2 weeks (Chinese patent medicine with clear antitumor indication) antitumor immunotherapy ≥ 4 weeks; Any investigational drug or treatment ≥ 4 weeks; Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4) ≥ 1 week; Organic Anion Transport Polypeptide (OATP) Inhibitors ≥ 1 week;

9. Failure of standard treatment, or intolerance, or absence of standard treatment, confirmed by pathology, HER2 expression (including IHC1+, IHC2+, IHC3+ and/or ISH\*+) or subjects with advanced/unresectable or metastatic solid tumors with HER2 exon 19 or 20 mutations (non-small cell lung cancer only). If only ISH\*, NGS reports are available, contact the Medical Monitor.

10. Failure of standard treatment, intolerance, or absence of standard treatment, confirmed by pathology, HER2 overexpression (IHC 3+ or IHC 2+ and ISH\* +) Advanced/unresectable or metastatic breast cancer.

11. Advanced breast cancer with low HER2 expression, unresectable, or metastatic breast cancer that has failed standard treatment, or is not tolerated, or has no standard treatment, is confirmed by pathology. (IHC 2+ and ISH\*- or ISH unknown, or IHC 1+).

12. Non-small cell lung cancer with a HER2 exon 19 or 20 mutation that has failed, or is not tolerated, or is confirmed by a documented pathology without standard treatment.

13. Advanced/unresectable or metastatic solid tumors with HER2 expression that have failed standard therapy, are not tolerated, or are without standard therapy, and are confirmed by pathology, with HER2 overexpression preferred. (IHC 3+ or IHC 2+ or ISH\* +) Adenocarcinoma of gastric and gastroesophageal junction; Other preferred tumor types include HER2 overexpression. (IHC 3+ or IHC 2+ or ISH\* +) Urothelial cancer, biliary tract cancer, endometrial cancer; Breast cancer and non-small cell lung cancer are excluded.

* ISH+: FISH or two-color in situ hybridization (DISH).

Exclusion Criteria

1. Clinically active brain metastases, defined as untreated and symptomatic, or requiring treatment with steroids or anticonvulsants to control associated symptoms. Subjects with treated asymptomatic brain metastases who do not require steroid therapy may be included in the study if they have recovered from the acute toxicity of radiation therapy.
2. Cardiovascular dysfunction or clinically significant cardiac conditions, including but not limited to:

* Symptomatic CHF (New York Heart Association classes II to IV) or severe cardiac arrhythmia requiring treatment
* History of myocardial infarction or troponin levels consistent with myocardial infarction (defined by the American College of Cardiology guidelines) within 6 months prior to the first dose, and unstable angina pectoris within 6 months prior to the first dose of study drug;
* QTcF prolongation at Screening \>460 milliseconds (ms) (male) and \>470 ms (female) except for right bundle branch block.
3. Clinically significant acute and chronic lung disease. (e.g., interstitial pneumonia, pulmonary infection, pulmonary fibrosis, and severe radiation pneumonitis), or subjects with suspected pulmonary disease based on imaging at screening, or subjects requiring oxygen.
4. People with known hypersensitivity to recombinant humanized anti-HER2 monoclonal antibody-DXd conjugate drugs and their components or to humanized monoclonal antibody products.
5. Poorly controlled pleural, ascites, or pericardial effusions.
6. Toxicity that has not resolved from prior antineoplastic therapy, defined as toxicity (other than alopecia) that has not resolved to ≤ Grade 1 or baseline levels, is at the discretion of the investigator for the eligibility of subjects with chronic Grade 2 toxicities.
7. The prior anthracycline exposure dose met the following criteria: adriamycin \> 500mg/m2; Epirubicin \>900mg/m2; Pirarubicin \> 950mg/m2; Mitoxanthraquinone \>120mg/m2; other (i.e. liposomal doxorubicin or other anthracycline \>equivalent to 500 mg/m2 of doxorubicin); If more than one anthracycline is used, the cumulative dose must not exceed the equivalent of 500 mg/m2 of doxorubicin.
8. There is an active infection requiring treatment with intravenous antibiotics, antivirals, or antifungals.
9. Known HIV infection.
10. Active hepatitis C virus infection. (HCV antibody positive and HCV-RNA higher than the upper limit of reference value); Active hepatitis B virus infection. (HBsAg positive and/or HBcAb positive and HBV-DNA quantitation ≥2000 IU/ml);, to be eligible for enrollment, subjects with chronic hepatitis B will have to agree to monthly DNA testing and receive appropriate antiviral therapy as indicated.
11. Live vaccine was administered within 30 days prior to the first dose of study drug.
12. Previous or current evidence of any concomitant disease, treatment, or laboratory abnormality that the investigator believes may confound the results of the trial or interfere with subject participation and compliance.
13. He has received treatment with an antibody-conjugated drug comprising a topoisomerase I inhibitor ezotecan derivative.
14. Breastfeeding women or women with confirmed pregnancy by a pregnancy test within 7 days prior to the first treatment.
15. Reluctant to contraception during the study and for at least 7 months after the last dose of study drug.
16. Subjects with multiple primary malignancies within the past 3 years, with the exception of fully resected non-melanoma skin cancer, cured disease in situ, cured contralateral breast cancer.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GeneQuantum Healthcare (Suzhou) Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Chinese PLA general hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

The First Affiliated Hospital of Haerbin Medical University

Haerbin, Heilongjiang, China

Site Status RECRUITING

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, Henan, China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

Affiliated Drum Tower Hospital, Medical School of Nanjing University

Nanjing, Jiangsu, China

Site Status RECRUITING

Shengjing hospital of China medical universty

Shenyang, Liaoning, China

Site Status RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, China

Site Status RECRUITING

Linyi Cancer Hospital

Linyi, Shandong, China

Site Status RECRUITING

Yantai Yuhuangding Hospital

Yantai, Shandong, China

Site Status RECRUITING

Fudan university Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

The First Affiliated Hospital of Xi'an University

Xi'an, Shangxi, China

Site Status RECRUITING

Suining Central Hospital

Suining, Sichuan, China

Site Status RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuang, China

Site Status RECRUITING

Tianjin medical university cancer institute & hospital

Tianjin, Tianjin Municipality, China

Site Status RECRUITING

Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yan Shi

Role: CONTACT

Phone: 0512-66526166

Email: [email protected]

Facility Contacts

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The FAHOZ University

Role: primary

Other Identifiers

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GQ1005-102

Identifier Type: -

Identifier Source: org_study_id