Clinical trial NCT04450732: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: GeneQuantum Healthcare (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-29
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Modified 3+3 Design
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent form and able to comply with the protocol;
2. Male and female subjects ≥18 years of age;
3. ECOG PS of 0 or 1, the estimated life expectancy ≥ 3 months;
4. LVEF ≥ 50% as determined by echocardiography (ECHO);
5. 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+.
6. 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.
7. 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.

   Chemotherapy or targeted therapy (including antibody drug therapy): ≥ 3 weeks (≥ 2 weeks for 5 flourouracil-based agents, folinate agents, and/or weekly paclitaxel; ≥ 2 weeks (or 5 half-lives, whichever is shorter) for tyrosine kinase inhibitors; ≥ 4 weeks for HER2-directed biologic therapies; ≥ 6 weeks for nitrosoureas or mitomycin C). Immunotherapy: ≥ 4 weeks. Strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor: ≥ 3 elimination half-lives . Any investigational agents or treatments: ≥ 4 weeks.
8. Patients without a history of acquired immunodeficiency syndrome (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 chemotherapy or radiotherapy;
2. 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);
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;
   * Corrected QT interval by Fridericia (QTcF) 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. Existing Grade ≥ 2 peripheral neuropathy;
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/m2 doxorubicin or equivalent;
9. Uncontrolled infection requiring i.v. of antibiotics, antivirals or antifungals;
10. 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;
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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs).
timeFrame: End of Cycle 1 (21-day cycle)
measure: Maximum Tolerated Dose (MTD) or Dose Recommended for Dose Expansion (DRDE)
timeFrame: 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:
measure: Incidence and Severity of Adverse Events (AEs)
timeFrame: from baseline to 30 days after last dose
measure: Number of Participants with Abnormal Laboratory Values
timeFrame: rom baseline through Cycle 8 (each cycle is 21 days) and up to 30 days from treatment discontinuationafter last dose
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of GQ1001
timeFrame: through study completion, an average of 1 year
measure: Peak Plasma Concentration of GQ1001 (Cmax)
timeFrame: through study completion, an average of 1 year
measure: Time at which the Cmax is Observed (Tmax)
timeFrame: through study completion, an average of 1 year
measure: Half Life of GQ1001 (T1/2)
timeFrame: through study completion, an average of 1 year
measure: Mean Residence Time of GQ1001 (MRT)
timeFrame: through study completion, an average of 1 year
measure: Volume of Distribution of GQ1001 (Vd)
timeFrame: through study completion, an average of 1 year
measure: Preliminary Efficacy of GQ1001 Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and CT of MRI scans
timeFrame: through study completion, an average of 1 year
measure: Immunogenicity
timeFrame: through study completion, an average of 1 year
measure: Preliminary Efficacy
timeFrame: through study completion, an average of 1 year
measure: Preliminary Efficacy
timeFrame: through study completion, an average of 1 year
measure: Preliminary Efficacy
timeFrame: through study completion, an average of 1 year
measure: Preliminary Efficacy
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Randwick
country: Australia
facility: Scientia Clinical Research Limited
state: New South Wales
city: Melbourne
country: Australia
facility: Cabrini Institute in Melbourne, Australia
state: Victoria
city: Bengbu
country: China
facility: The first affiliated hospital of Bengbu medical college
state: Anhui
city: Beijing
country: China
facility: Beijing Tongren Hospital Affiliated to Capital University of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Chinese PLA general hospital
state: Beijing
city: Guangzhou
country: China
facility: Southern Medical University Hospital in the south
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Huazhong University of Science and provincial Cancer Hospital Affiliated Union Hospital of Tongji Medical College
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Tumor Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital affiliated with the Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Affiliated to Shanghai Jiaotong University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China School of Medicine and West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: