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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 1, 2021

Interventions

  • Drug: GQ1001
    • anti-HER2 antibody drug conjugate

Arms, Groups and Cohorts

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

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

Participating in This Clinical Trial

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;

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • GeneQuantum Healthcare (Suzhou) Co., Ltd.
  • Collaborator
    • CRC Oncology
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Sarina Piha-Paul, Principal Investigator, M.D. Anderson Cancer Center
  • Overall Contact(s)
    • Paul Song, +86 13120762270, paul@genequantum.com

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