None listed
Conditions
Brief summary
This is first in human study of a new treatment drug, GQ1007 for patients with cancer that involves HER2-expression in solid tumors. This study aims to determine the maximum safest dose of GQ1007 that may be administered to cancer patients, firstly as a single therapy and secondly in combination with envafolimab therapy. Who is it for? You may be eligible for this study if you are an adult aged 18 or older, you have been diagnosed with any breast cancer, gastric cancer, gastroesophageal junction cancer, urothelial cancer, salivary gland carcinoma, gallbladder carcinoma, cholangiocarcinoma, or non-small cell lung cancer that involves solid tumours with HER2 gene expression. Additional heart and cognitive function tests will be conducted to determine suitability for enrolment. Study details This study will be conducted as four substudies (Parts 1-4), participants who choose to enrol in this study will only participate in one of the substudies. Participants enrolled into Parts 1 and 2 will receive subcutaneous injections (into the skin rather than a vein or muscle) of GQ1007 every 2 weeks for 2 years. Participants enrolled into Parts 3 and 4 will also receive subcutaneous injections of GQ1007 every 2 weeks for 2 years, and will also receive subcutaneous injections of envafolimab every 4 weeks for 2 years. All participants will undergo additional tests (including blood tests, echocardiograms and imaging) to assess the effect of the treatment on their cancer, and to monitor for side effects. Study participation is anticipated to be a maximum of approximately 26 months (up to 28 days for screening, up to 2 years of study treatment, and a Safety follow up Visit at 30 (+7) days after the last dose of any study treatment) plus long-term follow-up for subsequent anticancer therapy and overall survival. It is hoped this research will determine whether GQ1007 is safe and tolerable for patients with various cancer types. If GQ1007 is found to be safe, larger studies can then be conducted to determine the efficacy of this treatment which may then lead to improved quality of life and overall survival for future cancer patients. A Safety Review Committee (SRC) consisting of the Investigators and the Sponsor’s designated representatives will monitor safety throughout the study and make dose escalation decisions (including any decisions to explore intermediate, higher, or lower doses and/or alternative dosing schedules).
Interventions
This is first-in-human study including dose escalation and expansion of GQ1007-101 in subjects with human epidermal growth factor receptor 2 (HER2)-expressing advanced solid tumors.
GQ1007 is a HER2-targeting antibody-immune agonist conjugate (AIAC) which will be administered subcutaneously (SC) every two weeks as monotherapy or in combination with the checkpoint inhibitor envafolimab (400mg) administered SC every 4 weeks.
The study has 4 parts:
1. Part1 (Dose escalation for GQ1007 Monotherapy)
This is first-in-human study including dose escalation and expansion of GQ1007-101 in subjects with human epidermal growth factor receptor 2 (HER2)-expressing advanced solid tumors. GQ1007 is a HER2-targeting antibody-immune agonist conjugate (AIAC) which will be administered subcutaneously (SC) every two weeks as monotherapy or in combination with the checkpoint inhibitor envafolimab (400mg) administered SC every 4 weeks. The study has 4 parts: 1. Part1 (Dose escalation for GQ1007 Monotherapy) Up to five dose levels (0.3, 1.0, 2.0, 4.0, 6.0 mg/kg administered SC every two weeks) may be evaluated. Dose escalation will be guided by Bayesian Optimal Interval Design (BOIN) principles. Up to 30 participants are planned and not all the participants will receive each dose level. 2. Part 2 (Dose expansion for GQ1007 Monotherapy) to evaluate the safety and efficacy at the maximum tolerated dose (MTD)/ Dose recommended for dose expansion (DRDE) in subjects with selected HER2-expressing advanced solid tumors. Part 2 will have 3 cohorts and subject's tumor type will determine the subject's cohort in Part 2. 3. Part 3 (Dose escalation for GQ1007 + Envafolimab combination Therapy) Up to 6 GQ1007 dose levels ( 0.15, 0.3, 1.0, 2.0, 4.0, 6.0 mg/kg SC every two weeks) may be evaluated. Dose escalation will be guided by BOIN principles. Up to 30 participants are planned and not all the participants will receive each dose level. 4. Part 4 (Dose expansion for GQ1007 +Envafolimab combination therapy) will evaluate the safety and efficacy of GQ1007 at the MTD/DRDE in combination with envafolimab 400 mg every 4 weeks in subjects with selected HER2-expressing advanced solid tumors. GQ1007 and envafolimab administration will be performed by study site staff and documented in source documents and electronic case record forms (eCRF). Part 1 and Part 3 will be separated from Part 2 and 4 by a month. GQ1007 is supplied in single-dose glass vials, each containing 1 ml of 40 mg/ml liquid concentrate. Envafolimab is supplied in 300mg/1.5 ml vials. In Parts 1 and 2 (GQ1007 monotherapy), subjects will receive GQ1007 SC every two weeks on Day 1 each 2-week treatment cycle. In Parts 3 and 4, subjects will receive GQ1007 SC on day 1 of each 2-week treatment cycle and SC envafolimab 400 mg every 4 weeks (every other 2-week treatment cycle [cycle 1 Day 1, cycle 3 Day 1, cycle 5 Day 1]). For combination therapy, GQ1007 will be administered first and there will be a 30-40 minutes break between GQ1007 and envafolimab injections. The GQ1007 dose level for individual subjects in Parts 1 and 3 (dose escalation) will vary depending on the dose level enrolling subjects at the time of study entry. The GQ1007 dose level in Parts 2 and 4 will be the MTD /DRDE determined in Parts 1 and 3, respectively. The envafolimab dose will be 400 mg every 4 weeks in both Parts 3 and 4. If multiple study parts are open (enrolling) and a participants qualifies for multiple study parts, then the participant's assignment to a study part will be based on discussion between investigator and sponsor. As each dose level for monotherapy and/or combination therapy is cleared (i.e. dose escalation has advanced beyond that dose level), participants receiving treatment at lower dose levels based on cohort-assigned dose level may be escalated to a higher cleared dose level per investigator discretion and after discussion with and approval from sponsor. Participants on monotherapy will stay on monotherapy and subjects on combination therapy will stay on combination therapy. The treatment period in each part of the study includes up to 52 treatment cycles of two weeks per treatment cycle hence each each participant will receive the treatment for up to 2 years. A safety review committee (SRC) consisting of the investigators and the sponsor's designated representatives will monitor safety throughout the study and make dose escalation decisions (including any decisions to explore intermediate, higher, or lower doses and/or alternative dosing schedules).
Sponsors
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects more than or equal to 18 years of age with a life expectancy of more than 3 months. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3. Left ventricular ejection fraction (LVEF) more than or equal to 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before the first dose of study treatment. 4. Agrees to submit fresh tumor biopsy samples for biomarkers if any studied tumor is accessible. 5. Histologically or cytologically confirmed malignancy diagnosis and at least 1 measurable pathologically documented advanced/unresectable or metastatic solid tumor as assessed by RECIST 1.1. 6. Documented progressive disease, refractory to/intolerant of standard therapy, or there is no standard therapy. 7. Adequate organ function confirmed at screening and within 7 days before the first dose of study treatment as evidenced by platelet count (more than or equal to 100,000/mm3), hemoglobin (more than or equal to 8g/dl), Absolute neutrophil count (more than or equal to 1500/mm3), Serum creatinine (less than or equal to 1.5 × upper limit of normal[ULN], or estimated creatinine clearance more than or equal to 60 mL/min (Cockcroft-Gault formula), alanine transaminase and aspartate transaminase less than or equal to 2.5 × ULN (less than or equal to 5 × ULN if liver metastases are present), total bilirubin (less than or equal to 1.5 × ULN or less than or equal to 2 × ULN for subjects with Gilbert’s Syndrome), Prothrombin time and activated partial thromboplastin time (less than or equal to 1.5 × ULN). 8. Adequate washout period before the first treatment -For any major surgery, radiation therapy, immunotherapy, and any investigational agents or treatments- more than or equal to 4 weeks, -For autologous transplants - more than or equal to 3 months, -For hormonal therapy - more than or equal to 2 weeks, -For chemotherapy or targeted therapy- more than or equal to 2 weeks (for 5-flourouracil based agents, folinate agents, and/or weekly paclitaxel, tyrosine kinase inhibitors); more than or equal to 4 weeks for HER2-directed biologic therapies; more than or equal to 6 weeks for nitrosoureas or mitomycin C; more than or equal to 3 weeks for any other chemotherapy/targeted therapy. Additional inclusion criteria for Part 1 and Part 3 9. Has the protocol specified malignancies such as breast cancer, gastric cancer, gastroesophageal junction cancer, urothelial cancer, salivary gland carcinoma, gallbladder carcinoma, cholangiocarcinoma, or non-small cell lung cancer. Additional inclusion criteria for Part 2 and Part 4 10. Agrees to provide a HER2 test report from tumor biopsy performed within the past 6 months or an archived tumor sample collected within the past 6 months, and if neither is available, a fresh tumor biopsy to confirm HER2 status if any studied tumor is accessible. Additional inclusion criteria for Part 2a 11. Has breast cancer with HER2 overexpression (immunohistochemistry [IHC] 3+ or [IHC 2+ and in situ hybridization]). Additional inclusion criteria for Part 2b 12. Has breast cancer with HER2 low expression (immunohistochemistry [IHC] 2+ or ISH or IHC 1+). Subjects with HER2 low expression metastatic breast cancer who have exhausted treatments that can confer any clinically meaningful benefit are also eligible. Additional inclusion criteria for Part 2c 13. Subject has either a solid malignant tumor with HER2 expression or HER2 mutation. Additional Inclusion criteria for Part 4 14. Subjects either have HER2 overexpressing breast cancer and gastric or gastroesophageal junction adenocarcinoma: IHC 3+ or [IHC 2+ and in situ hybridization] or HER2 low expressing breast cancer: IHC 1+ or [IHC 2+ but ISH] or any other solid malignant tumor with HER2 HER2 expression or HER2 mutation.
Exclusion criteria
1. Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. 2. Conditions requiring systemic treatment with either corticosteroids (more than 10 mg daily prednisone equivalent) within 7 days or taking any other immunosuppressive medication within 14 days prior to the first dose of study treatment. 3. Active autoimmune disease that required systemic treatment (disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. 4. Prior organ or tissue allograft. 5. History of Grade 3 or higher toxicity related to prior T cell agonist or checkpoint inhibitor. 6. Poorly controlled diarrhea (e.g., watery stool, uncontrolled bowel movement with drugs, Grade more than or equal to 2 ). 7. Cardiovascular dysfunction or clinically significant cardiac disease. 8. Medical history of clinically significant lung disease. 9. Known hypersensitivity to either the drug substances or inactive ingredients in the drug product. 10. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade 1 or less or baseline. 11. Cumulative anthracycline dose greater than 360 mg/m2 doxorubicin or equivalent. 12. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. 13. Known human immunodeficiency virus (HIV) infection. 14. Active infection with hepatitis C or hepatitis B except that subjects with occult or prior hepatitis B infection may be included if Hepatitis B Virus's Deoxyribonucleic acid (DNA) is undetectable at the time of screening, and these subjects must be willing to monthly DNA testing and appropriate antiviral therapy as indicated. 15. A positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a certified nucleic acid test within the last 30 days before the first dose of study treatment. 16. Receipt of a live vaccine within 30 days prior to the first dose of study treatment. 17. Pregnant or lactating women 18. Unwilling to use adequate contraceptive methods during the study and for at least 7 months after the last dose of study tratments. Additional exclusion criteria for Part 2 and Part 4 19. 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.
Outcome results
None listed