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

Phase 1

Recruiting

• Conditions: HER2-Positive Advanced Solid Tumors; Cancer - Any cancer

• Registration Number: ACTRN12620000592943
• Lead Sponsor: Conjugate Light (Australia) Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-21
• Last Update Posted: 22 February 2021

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Patients who are voluntary to participate in this clinical study, able to understand the study procedure, and have signed the informed consent form.

2. Male or female subjects 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) greater than or equal to 50% by echocardiography

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: FISH or DISH

6. Has adequate organ function within 7 days before the first treatment defined as:
- Platelet count greater than or equal to 100 000/mm^3
- Hemoglobin (Hb) greater than or equal to 9 g/dL
- Absolute neutrophil count (ANC) greater than or equal to 1500/mm^3
- Serum Creatinine less than or equal to 1.5 × ULN, or creatinine clearance greater than or equal to 60 mL/min (using Cockcroft-Gault formula).
- AST/ALT less than or equal to 2.5 × ULN (if liver metastases are present, less than or equal to 5 × ULN)
- Total bilirubin less than or equal to 1.5 × ULN
- Prothrombin time and activated partial thromboplastin time less than or equal 1.5 × ULN

7. Has adequate treatment washout period before the first treatment, defined as:
- Major surgery greater than or equal to 4 weeks
- Radiation therapy greater than or equal to 4 weeks (if palliative stereotactic radiation therapy without abdominal, greater than or equal to 2 weeks)
- Autologous transplantation greater than or equal to 3 months
- Hormonal therapy greater than or equal to 2 weeks
- Chemotherapy or other target therapy (including antibody drug therapy) greater than or equal to 3 weeks (greater than or equal to 2 weeks for 5-fluorouracil-based agents, HER2-directed therapies greater than or equal to 4 weeks; folinate agents and/or weekly Paclitaxel; greater than or equal to 6 weeks for nitrosoureas or mitomycin C);
- Immunotherapy greater than or equal to 4 weeks
- CYP3A4 strong inhibitor greater than or equal to 3 elimination half-lives of the inhibitor
- Any investigational agents or treatments greater than or equal to 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 as defined by;
- Has a medical history of symptomatic CHF (NYHA classes II-IV) or serious cardiac arrhythmia requiring treatment;
- Has a medical history of myocardial infarction or unstable angina within 6 months before registration;
- Has a QTc prolongation to greater than 450 millisecond (ms) in males and greater than 470 ms in females based on 12-lead ECG in triplicate;

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 greater than or equal to 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. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, grade less than or equal to 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the Investigator;

8. Cumulative anthracycline dose greater than 360 mg/m2 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;

Study & Design

• Study Type: Interventional
• Study Design: Not specified