Clinical Trials /

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

NCT04450732

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety of GQ1001 in Adult Patients With HER2-Positive Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GQ1001X2101
  • NCT ID: NCT04450732

Conditions

  • HER2-positive Breast Cancer
  • HER2-positive Gastric Cancer
  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
GQ1001GQ1001 1.2 mg/kg

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
GQ1001 1.2 mg/kgExperimental1.2 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.
  • GQ1001
GQ1001 2.4 mg/kgExperimental2.4 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.
  • GQ1001
GQ1001 3.6 mg/kgExperimental3.6 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.
  • GQ1001
GQ1001 4.8 mg/kgExperimental4.8 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.
  • GQ1001
GQ1001 6.0 mg/kgExperimental6.0 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.
  • GQ1001

Eligibility 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;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) and/or Dose Limiting Toxicities (DLTs).
Time Frame:End of Cycle 1 (21-day cycle)
Safety Issue:
Description: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

Measure: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 Issue:
Description:Safety and Tolerability of GQ1001
Measure: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 Issue:
Description:Safety and Tolerability of GQ1001
Measure:Area Under the Plasma Concentration Versus Time Curve (AUC) of GQ1001
Time Frame:Cycle 1 through Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Peak Plasma Concentration of GQ1001 (Cmax)
Time Frame:Cycle 1 through Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Time at which the Cmax is Observed (Tmax)
Time Frame:Cycle 1 through Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Half Life of GQ1001 (T1/2)
Time Frame:Cycle 1 through Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Mean Residence Time of GQ1001 (MRT)
Time Frame:Cycle 1 through Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Volume of Distribution of GQ1001 (Vd)
Time Frame:Cycle 1 through Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:GeneQuantum Healthcare (Suzhou) Co., Ltd.

Trial Keywords

  • HER2-positive
  • Advanced Solid Tumor

Last Updated

June 25, 2020