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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04450732
Recruitment Status : Not yet recruiting
First Posted : June 29, 2020
Last Update Posted : June 29, 2020
Sponsor:
Collaborator:
CRC Oncology
Information provided by (Responsible Party):
GeneQuantum Healthcare (Suzhou) Co., Ltd.

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

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer HER2-positive Gastric Cancer Advanced Solid Tumor Drug: GQ1001 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Modified 3+3 Design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-In-Human, Multicenter, Open-Label, Study of GQ1001, a HER2 Targeted Antibody-Drug Conjugate, Administered Intravenously, in Adult Patients With HER2-Positive Advanced Solid Tumors
Estimated Study Start Date : July 10, 2020
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GQ1001 1.2 mg/kg
1.2 mg/kg GQ1001 administered intravenously. Patients are dosed on a 21 day treatment cycle until disease progression occurs, unacceptable toxicity occurs, or if they voluntarily withdraw their consent.
Drug: GQ1001
anti-HER2 antibody drug conjugate

Experimental: GQ1001 2.4 mg/kg
2.4 mg/kg GQ1001 administered intravenously. Patients are dosed on a 21 day treatment cycle until disease progression occurs, unacceptable toxicity occurs, or if they voluntarily withdraw their consent.
Drug: GQ1001
anti-HER2 antibody drug conjugate

Experimental: GQ1001 3.6 mg/kg
3.6 mg/kg GQ1001 administered intravenously. Patients are dosed on a 21 day treatment cycle until disease progression occurs, unacceptable toxicity occurs, or if they voluntarily withdraw their consent.
Drug: GQ1001
anti-HER2 antibody drug conjugate

Experimental: GQ1001 4.8 mg/kg
4.8 mg/kg GQ1001 administered intravenously. Patients are dosed on a 21 day treatment cycle until disease progression occurs, unacceptable toxicity occurs, or if they voluntarily withdraw their consent.
Drug: GQ1001
anti-HER2 antibody drug conjugate

Experimental: GQ1001 6.0 mg/kg
6.0 mg/kg GQ1001 administered intravenously. Patients are dosed on a 21 day treatment cycle until disease progression occurs, unacceptable toxicity occurs, or if they voluntarily withdraw their consent.
Drug: GQ1001
anti-HER2 antibody drug conjugate




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) and/or Dose Limiting Toxicities (DLTs). [ Time Frame: End of Cycle 1 (21-day cycle) ]
    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.


Secondary Outcome Measures :
  1. Incidence and Severity of Adverse Events (AEs) [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) and up to 30 days from treatment discontinuation ]
    Safety and Tolerability of GQ1001

  2. Number of Participants with Abnormal Laboratory Values [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) and up to 30 days from treatment discontinuation ]
    Safety and Tolerability of GQ1001

  3. Area Under the Plasma Concentration Versus Time Curve (AUC) of GQ1001 [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) ]
  4. Peak Plasma Concentration of GQ1001 (Cmax) [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) ]
  5. Time at which the Cmax is Observed (Tmax) [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) ]
  6. Half Life of GQ1001 (T1/2) [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) ]
  7. Mean Residence Time of GQ1001 (MRT) [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) ]
  8. Volume of Distribution of GQ1001 (Vd) [ Time Frame: Cycle 1 through Cycle 8 (each cycle is 21 days) ]
  9. Preliminary Efficacy of GQ1001 Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and CT of MRI scans [ Time Frame: through study completion, an average 24 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent form and able to comply with the protocol;
  2. Male or female 18 years of age and older;
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening;
  4. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography (ECHO);
  5. Patients must have pathologically documented advanced/unresectable or metastatic solid tumor with HER2 overexpression/expression (refer to the following definition) that is refractory to standard therapy or for which there is no standard available therapy:

    • Advanced/unresectable or metastatic breast cancer: IHC 3+ or IHC 2+/ISH* +;
    • Advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: IHC 3+ or IHC 2+/ISH* +;
    • Other advanced/unresectable or metastatic solid malignant tumor: determined by IHC, FISH, 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 immunohistochemistry (IHC) result is 3+. ISH assay should be performed to confirm HER2 positivity when IHC result is 2+.
  6. Has adequate organ function within 7 days before the first treatment defined as:

    • Platelet count ≥ 100 000/mm^3
    • Hemoglobin ≥ 9 g/dL
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3
    • Serum Creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min (using Cockcroft-Gault formula).
    • AST/ALT ≤ 2.5 × ULN (if liver metastases are present, ≤ 5 × ULN)
    • Total bilirubin ≤ 1.5 × ULN
    • Prothrombin time and activated partial thromboplastin time ≤ 1.5 × ULN
  7. Has adequate treatment washout period before the first treatment, defined as:

    • Major surgery ≥ 4 weeks
    • Radiation therapy ≥ 4 weeks (if palliative stereotactic radiation therapy without abdominal, ≥ 2 weeks)
    • Autologous transplantation ≥ 3 months
    • Hormonal therapy ≥ 2 weeks; or per Investigator's discretion for breast cancer patients
    • Chemotherapy or other target therapy (including antibody drug therapy) ≥ 3 weeks (≥ 2 weeks for 5-fluorouracil-based agents, folinate agents, and/or weekly paclitaxel; ≥ 2 weeks (or 5 half-lives, whichever is shorter) for tyrosine kinase inhibitors; HER2- directed therapies ≥ 4 weeks; ≥ 6 weeks for nitrosoureas or mitomycin C);
    • Immunotherapy ≥ 4 weeks
    • CYP3A4 strong inhibitor ≥ 3 elimination half-lives
    • Any investigational agents or treatments ≥ 4 weeks
  8. Patients without a history of AIDS-defining opportunistic infections or with a history of AIDS-defining opportunistic infections and have not had an opportunistic infection within the past 12 months may be enrolled per the discretion of the Investigator.

Exclusion Criteria:

  1. 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 radiotherapy;
  2. Any hematologic malignancies, including leukemia (any form), lymphoma, and multiple myeloma;
  3. 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;
    • QTc prolongation of > 450 milliseconds (ms) in males and > 470 ms in females;
  4. 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;
  5. Known hypersensitivity to either the drug substances or inactive ingredients in the drug product;
  6. Grade ≥ 2 peripheral neuropathy (Note: for patients who relapsed or refractory to Kadcyla®, patients who have grade ≥ 2 peripheral neuropathy may be eligible per the discretion of the Investigator after discussion with the Sponsor);
  7. 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;
  8. Cumulative anthracycline dose > 360 mg/m^2 doxorubicin or equivalent;
  9. Uncontrolled infection requiring i.v. of antibiotics, antivirals or antifungals;
  10. Active infection of hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g. HCV RNA (qualitative) is detected);
  11. 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;
  12. Women who are lactating or pregnant, as confirmed by pregnancy test within 7 days before first treatment;
  13. Male and female subjects who are unwilling to use adequate contraceptive methods (e.g. concomitant use of a spermicidal agent, barrier contraceptive, or/and intrauterine contraceptive) during the study and for at least 7 months after the last dose of GQ1001;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04450732


Contacts
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Contact: Paul Song +86 13120762270 paul@genequantum.com
Contact: Katherine E Young +1 9257599874 katherine.young@crconc.org

Locations
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United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Contact: Katrien C Van Roosbroeck       kvan1@mdanderson.org   
Principal Investigator: Sarina Piha-Paul, MD         
Sponsors and Collaborators
GeneQuantum Healthcare (Suzhou) Co., Ltd.
CRC Oncology
Investigators
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Principal Investigator: Sarina Piha-Paul M.D. Anderson Cancer Center
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Responsible Party: GeneQuantum Healthcare (Suzhou) Co., Ltd.
ClinicalTrials.gov Identifier: NCT04450732    
Other Study ID Numbers: GQ1001X2101
First Posted: June 29, 2020    Key Record Dates
Last Update Posted: June 29, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GeneQuantum Healthcare (Suzhou) Co., Ltd.:
HER2-positive
Advanced Solid Tumor
Additional relevant MeSH terms:
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Neoplasms