A Phase I/II, Multicenter, Open-Label, Dose-Escalation and Extension Study of GQ1010(an Anti-Trop2 ADC) in Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Dose Escalation
- Conditions
- Advanced Malignant Solid Tumors
- Sponsor
- GeneQuantum Healthcare (Suzhou) Co., Ltd.
- Enrollment
- 260
- Locations
- 5
- Primary Endpoint
- Phase Ib: Recommended phase II dose (RP2D)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief 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
Detailed Description
This is a Phase 1/2, first in human (FIH), open-label, multicenter study of GQ1010, a Trop-2 directed antibody-drug conjugate (ADC), in participants with previously treated, advanced solid tumors. The study comprises 3 parts: a Phase 1a Dose Escalation, a Phase 1b Dose Expansion, and Phase 2 study. The Phase 1a will investigate the safety and tolerability of GQ1010 and identify one or more recommended doses for expansion (RDEs) and the maximum-tolerated dose (MTD) (if exists). Once the RDEs has been established, Phase 1b will open to identify the recommended phase 2 dose (RP2D) of GQ1010. Then the phase 2 study will open to investigate the preliminary efficacy of GQ1010 in 5 cohorts with different tumor types.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, ≥18 years old.
- •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.
- •Has a life expectancy of ≥ 3 months.
- •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.
- •Agreed to provide archived tumor tissue specimens (unstained 10 surgical specimens \[thickness 4-5μm\] was suggested 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.
- •Measurable tumor lesion based on Response Evaluation Criteria in Solids Tumors (RECIST) version 1.
- •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 .
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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.
Exclusion Criteria
- •Is a lactating mother or pregnant as confirmed by pregnancy tests;
- •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%)
Arms & Interventions
Dose Escalation
GQ1010 will be administered intravenously every 21 days or every 14 days. Dose Escalation will be guided by Bayesian Optimal Interval (BOIN) Design. Multiple dose grouping
Intervention: Dose Escalation
Dose Expansion1
GQ1010 at the recommended doses for Expansion (RDEs) . Dose expansion will further evaluate the safety and tolerability in advanced malignant solid tumor subjects.
Intervention: Dose Expansion1
Dose Expansion2
GQ1010 at the recommended doses for Expansion (RDEs). Dose expansion will further evaluate the safety and tolerability in advanced malignant solid tumor subjects.
Intervention: Dose Expansion2
Dose Expansion3
GQ1010 at the recommended doses for Expansion (RDEs) . Dose expansion will further evaluate the safety and tolerability in advanced malignant solid tumor subjects.
Intervention: Dose Expansion3
phase II
GQ1010 at the recommended phase II dose (RP2D). Dose expansion will evaluate preliminary efficacy in different types of malignant solid tumor in five cohorts.
Intervention: phase II
Outcomes
Primary Outcomes
Phase Ib: Recommended phase II dose (RP2D)
Time Frame: After each cohort completes the safety and efficacy evaluation, an average of 6 months
The SRC will also determine the RP2D based on the totality and efficacy of data for all tested dose levels.
Phase I/II: Incidence and Severity of Adverse Events (AEs)
Time Frame: Screening up to study completion, an average of 1 year
Incidence and severity of Treatment-emergent adverse events, treatment-related adverse events and serious adverse events, according to NCI-CTCAE Version 5.0 (The number of participants who had treatment-related side effects in population who had received one therapy at least). Incidence and severity of TEAEs, TRAE and SAE
Phase Ia: Dose Limiting Toxicities (DLTs)
Time Frame: 21 days or 28 days
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.
Phase Ia: Maximal Tolerance Dose (MTD) or recommended doses for dose expansion (RDEs)
Time Frame: After each cohort completes the DLT observation period or has a DLT or becomes not DLT-evaluable
The SRC will determine the MTD/RDEs based on the totality of data for all tested dose levels.
Phase II: Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame: Screening up to study completion, an average of 1 year
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). ORR is evaluated by the number of participants with best overall response of CR and PR.
Secondary Outcomes
- Maximum concentration (Cmax) of GQ1010(Screening up to study completion, an average of 1 year)
- Time of peak plasma concentration (Tmax)(Screening up to study completion, an average of 1 year)
- Area under the plasma concentration time curve (AUC) of GQ1010(Screening up to study completion, an average of 1 year)
- Terminal half-life (T1/2) of GQ1010(creening up to study completion, an average of 1 year)
- Progression-free survival (PFS) determined by investigators according to RECIST 1.1(Screening up to study completion, an average of 1 year)
- Disease control rate (DCR) determined by investigators according to RECIST 1.1(Screening up to study completion, an average of 1 year)
- Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Screening up to study completion, an average of 1 year)
- Duration of response (DOR) determined by investigators according to RECIST 1.1(Screening up to study completion, an average of 1 year)
- Overall survival (OS) (only in dose expansion stage)(Screening up to study completion, an average of 1 year)
- Immunogenicity (anti-drug antibody ADA)(Screening up to study completion, an average of 1 year)