Trial Title:
A Study of GQ1010 in Subjects With Advanced Solid Tumors
NCT ID:
NCT06464055
Condition:
Advanced Malignant Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dose Escalation
Description:
GQ1010
Arm group label:
Dose Escalation
Intervention type:
Drug
Intervention name:
Dose Expansion1
Description:
GQ1010 dose1
Arm group label:
Dose Expansion1
Intervention type:
Drug
Intervention name:
Dose Expansion2
Description:
Drug: GQ1010 dose2
Arm group label:
Dose Expansion2
Intervention type:
Drug
Intervention name:
phase II
Description:
Drug: GQ1010 RP2D
Arm group label:
phase II
Summary:
This is an open-label, phase I/II study to evaluate the safety, tolerability,
pharmacokinetics and immunogenicity of GQ1010 and preliminary anti-tumor efficacy in
advanced malignant solid tumor subjects
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female, ≥18 years old.
2. Is able to provide written informed consent and is willing and able to comply with
the protocol prior to initiation of any study-related tests or procedures.
3. Has a life expectancy of > 3 months.
4. With histologically or cytologically confirmed locally advanced or metastatic solid
malignant tumors with epithelial derived malignancy has relapsed or progressed
following local standard treatments, or for which no standard treatment is
available. Priority for inclusion but not limited to the following types of cancer:
gastric adenocarcinoma/gastroesophageal junction cancer, breast cancer (triple
negative and hormone receptor-positive, HER2 negative), colorectal cancer,
cholangiocarcinoma, pancreatic cancer, endometrial cancer, ovarian cancer, cervical
cancer, etc.
5. Suggested to provide archived tumor tissue specimens (unstained 10 surgical
specimens [thickness 4-5μm] or fresh tissue samples of primary or metastatic sites
within 3 years..
Note: Trop-2 expression was not used to confirm participant eligibility; Tissue
samples will be used for subsequent analysis of Trop-2 expression levels and other
biomarkers.
6. Measurable tumor lesion based on Response Evaluation Criteria in Solids Tumors
(RECIST) version 1.1.
7. Subjects had confirmed disease progression during or after the most recent treatment
for locally advanced or metastatic disease, or subjects would not benefit from the
former treatment assessed by the investigator .
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. If of reproductive/child-bearing potential(male and female) must agree to use
reliable contraceptive measures (include hormonal contraceptives, barrier
contraception or abstinence) with their partners during and upon completion of the
study and for at least 7 months after the last dose of study drug.
10. Has adequate bone marrow reserve and organ function (no transfusion or
hematopoietic-stimulating factor therapy within 14 days):
- Hemoglobin (HGB) ≥ 9 g/dl
- Absolute neutrophil count (ANC) ≥ 1,500/mm3,
- Platelet count (PLT) ≥ 100,000/mm3,.
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance (Ccr) ≥ 50 ml/min
(calculated according to the cockcroft-gault formula),
- Total bilirubin (TBIL) ≤ 1.5 × ULN (gilbert's syndrome, TBIL ≤ 3 × ULN),
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN
(with liver metastases ≤ 5.0 × ULN)
- International normalized ratio of prothrombin (INR) ≤ 1.5 × ULN, or prothrombin
time (PT) ≤ 1.5 × ULN,
- Activated partial thromboplastin time (APTT) ≤1.5 × ULN. Subjects receiving
anticoagulant therapy must have INR and/or APTT≤ the upper limit of the
therapeutic range intended for use,
- Left ventricular ejection fraction ≥50% by echocardiography
11. Has an adequate treatment washout period prior to initial treatment.
12. 3a: Has a pathologically documented HER2 negative (IHC 2+ and ISH* - or ISH unknown,
or IHC 1+) advanced/unresectable or metastatic gastric
adenocarcinoma/gastroesophageal junction carcinoma(GC/GJC) that relapsed or
progressed after standard therapy (at least first-line chemotherapy with or without
immune checkpoint inhibitor), or no standard therapy available. Those who
relapsed/progressed within 6 months of prior adjuvant/neoadjuvant systemic therapy
are not required to receive an additional line of therapy in order to be eligible.
13. 3b: Has a pathologically documented advanced/unresectable or metastatic triple
negative breast cancer(TNBC) that relapsed or progressed after standard treatment
(at least first-line chemotherapy), or no standard treatment available.
14. 3b: Has a pathologically documented advanced, or unresectable, or metastatic HER2
negative(IHC2+ with ISH*- or ISH unknown, or IHC1+) HR+BC, is documented refractory
or resistant to standard therapy (Was previously treated with a minimum of 1 and a
maximum of 4 prior lines of chemotherapy in the advanced/metastatic setting), or no
standard therapy available :
- All subjects must have previously received antitumor endocrine therapy, CDK-4/6
inhibitor therapy, and taxanes;
- Those who relapsed/progressed within 12 months of prior adjuvant/neoadjuvant
systemic therapy are not required to receive an additional line of therapy in
order to be eligible.;
- Subjects with HER2 low expression who have progressed after treatment with
anti-HER2-ADC (such as T-DXd) are admitted.
15. 3c: Has a pathologically documented advanced, unresectable, or metastatic colorectal
cancer is documented refractory or resistant to standard treatment (at least 2 prior
lines systemic therapy, including 5-FU-based chemotherapy and anti-VEGF or
anti-EGFR-mAb therapy), or no standard therapy available.
• Has not progressed or relapsed within 3 months of therapy with irinotecan.
16. 3d: Has a pathologically documented advanced/unresectable or metastatic cervical
cancer or endometrial cancer that relapsed or progressed after standard therapy (at
least first-line chemotherapy with or without immune checkpoint inhibitor), or no
standard therapy available.
17. 3d: Pathologically documented unresectable or metastatic platinum-resistant ovarian
cancer that has relapsed or progressed within 6 months of platinum-based
chemotherapy, or no standard therapy available. .
18. 3d: Pathologically documented unresectable or metastatic platinum-sensitive ovarian
cancer that has relapsed or progressed at least 6 months after the most recent
platinum-based chemotherapy , or no standard therapy available. .
19. 3e: Has a pathologically documented advanced/unresectable or metastatic Biliary
tract carcinoma(BTC) that relapsed or progressed after standard therapy (at least
first-line chemotherapy with or without immune checkpoint inhibitor), or no standard
therapy available.
20. 3e: Has a pathologically documented unresectable or metastatic Head and neck
squamous cell carcinoma(HNSCC) that relapsed or progressed after at least 1 prior
lines of therapy including chemotherapy and ICI or EGFR mAb (in combination or
sequential ), or no standard therapy available.
21. 3e: Has a pathologically documented unresectable or metastatic pancreatic cancer
that relapsed or progressed after least 1 prior line of systemic therapy, or no
standard therapy available. Those who relapsed/progressed within 6 months of prior
adjuvant/neoadjuvant systemic therapy are not required to receive an additional line
of therapy in order to be eligible. And has not progressed or relapsed within 3
months of therapy with irinotecan.
Exclusion Criteria:
1. Is a lactating mother or pregnant as confirmed by pregnancy tests;
2. Clinically significant concurrent diseases, including but not limited to:
- Heart failure with New York Heart Association [NYHA] Grade II to IV
- Myocardial infarction, unstable angina pectoris, or stroke within 6 months
prior to the first dose of study drug
- Newly diagnosed thromboembolic events requiring therapeutic intervention within
6 months prior to the first dose of study drug
- Severe aortic stenosis
- Uncontrolled arrhythmia
- Congenital long QT syndrome
- Prolonged QT interval (QTcF) as corrected by Fredericia > 470 msec according to
12-lead ECG
- Uncontrolled hypertension (systolic blood pressure ≥180 mmHg and/or diastolic
blood pressure ≥110 mmHg) or diabetes (HbA1c ≥9.0%)
- Clinically significant active infection requiring systemic antibiotic,
antiviral, or antifungal treatment
- Poorly controlled pleural effusion, pericardial effusion, or ascites with
clinical symptoms requiring drainage (poorly controlled as carrying a drainage
tube or drainage frequency ≥1 / week).;
3. Clinically active brain metastases, defined as untreated and symptomatic, or
requiring therapy with steroids or anticonvulsants to control associated symptoms.
Has leptomeningeal carcinomatosis, has brain stem metastasis, spinal cord
compression. A minimum of 4 weeks must have elapsed between the end of whole brain
surgery and study enrollment. 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.
4. Subjects have had other primary malignancies within the last 3 years (other than
sufficiently resected non-melanoma skin cancer, cured in situ disease, cured other
solid tumors, and/or contralateral breast cancer).
5. Has a history of or currently have interstitial lung disease (including but not
limited to pulmonary fibrosis, radiation pneumonia) that requires steroids, or
cannot be ruled out by imaging; Patients who currently have active pneumonia or
pulmonary function tests that confirm severe impairment of lung function, and
patients who require oxygen inhalation.
6. Clinically severe pulmonary compromise resulting from intercurrent pulmonary
illnesses including, but not limited to, any underlying pulmonary disorder (ie,
pulmonary emboli within 3 months of the study enrollment, severe asthma, severe
COPD, restrictive lung disease, pleural effusion etc.), or any autoimmune,
connective tissue or inflammatory disorders with pulmonary involvement (ie,
Rheumatoid arthritis, Sjögren's, sarcoidosis etc.), or prior pneumonectomy.
7. Participants who are active or have a clear history of inflammatory bowel disease,
or who have esophageal and gastric varices, gastrointestinal obstruction, severe
ulcers, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal
bleeding within 6 months prior to the first dose of study drug;
8. Imaging (CT or MRI) confirmed that the tumor surrounds important blood vessels or
the investigator determines that the tumor is highly likely to invade important
blood vessels and cause fatal massive bleeding during subsequent studies;
9. Has an active hepatitis C (HCV antibody positive with HCV RNA above the reference
limit) or hepatitis B virus infection (e.g., hepatitis B surface antigen [HBsAg]
positive with HBV DNA≥2000 IU/mL); tuberculosis (evidence of active TB infection
within 1 year), syphilis (positive for both specific and non-specific antibodies to
treponema pallidum); people infected with human immunodeficiency virus (HIV
positive).
10. Grade 2 or above corneal disease with clinical symptoms.
11. Previously received Trop-2 targeted therapy, including Trop-2 ADC.
12. Previously received ADC therapy with topoisomerase I inhibitors as payload
(HR+HER2-BC cohort excepted).
13. Has unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia, chemotherapy-induced grade 2 neuropathy, endocrinopathies
which can be well controlled by hormone replacement therapy and other toxicities
that remained grade 2 but chronically stable evaluated by the investigator ) not yet
resolved to the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI CTCAE) version 5.0, Grade ≤1 or baseline.
14. Has a history of severe hypersensitivity reactions to either the drug substances or
inactive ingredients of GQ1010. Has a history of severe hypersensitivity reaction to
other monoclonal antibodies.
15. Has any other past or current evidence of any concomitant disease, treatment, or
laboratory test abnormality that would increase the safety risk to the subject or
interfere with participation of the subject or evaluation of the clinical study in
the opinion of the investigator.
16. Nucleic acid test positive for acute severe respiratory syndrome coronavirus type 2
(SARS-CoV-2) within 30 days prior to the first administration of the study drug.
17. Administered live vaccine within 30 days prior to the first administration of the
study drug.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Lin Shen, MD. Ph.D
Investigator:
Last name:
Lin Shen, MD. Ph.D
Email:
Principal Investigator
Facility:
Name:
Department of Medical Oncology, Harbin Medical University Cancer Hospital
Address:
City:
Harbin
Country:
China
Status:
Recruiting
Contact:
Last name:
Qingyuan Zhang, MD. Ph.D
Investigator:
Last name:
Qingyuan Zhang, MD. Ph.D
Email:
Principal Investigator
Facility:
Name:
Tianjin medical university cancer institute & hospital
Address:
City:
Tianjin
Country:
China
Status:
Recruiting
Contact:
Last name:
Ting Deng, MD. Ph.D
Investigator:
Last name:
Ting Deng, MD. Ph.D
Email:
Principal Investigator
Facility:
Name:
Hubei Cancer Hospital
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Contact:
Last name:
Yi Huang, MD. Ph.D
Investigator:
Last name:
Yi Huang, MD. Ph.D
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Min Yan, MD. Ph.D
Investigator:
Last name:
Min Yan, MD. Ph.D
Email:
Principal Investigator
Start date:
May 23, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Agency class:
Industry
Source:
GeneQuantum Healthcare (Suzhou) Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06464055
