Neoplasms, Malignant
Conditions
Brief summary
This study will evaluate the safety, of SIM0689 and how the body processes it, how it affects the body, and its early signs of activity against tumors when given alone to Adult Participants with Locally Advanced or Metastatic Solid Tumors. The study has a dose escalation part to find the highest dose that can be given safely, or recommended dose (RD) for SIM0689 when given alone, and a dose expansion part in subjects with specific tumor types treated with SIM0689 as a single agent at RD.
Interventions
DRUGSIM0689 for Injection
SIM0689 for Injection is a Programmed Cell Death Protein 1(PD1) / Vascular Endothelial Growth Factor (VEGF) bispecific antibody.
Sponsors
Jiangsu Simcere Pharmaceutical Co., Ltd.
Shanghai Xianwei Medical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* In dose-escalation cohorts (Part 1), histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy. * In the dose-expansion cohorts (Part 2), histologically or cytologically confirmed selected advanced solid tumors. * Subjects must have at least one measurable lesion according to RECIST Version1.1. * Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1. * Adequate organ function. * Available archived tumor tissue sample to allow for correlative biomarker studies. If unavailable or unsuitable, the subject must consent and undergo fresh tumor biopsy. * Life expectancy ≥12 weeks. * Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 180 days after the last dose.
Exclusion criteria
* Symptomatic brain metastases. * Serious non-healing wounds, ulcers or fractures. * Toxicity from previous treatment has to restore to ≤ grade 1. * Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment. * Use of aspirin (\> 325 mg/day) within 6 months prior to the first dose. * Active hepatitis B or hepatitis C. * Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). * Known hereditary or acquired predisposition to bleeding and thrombosis. * History of gastrointestinal perforation, gastrointestinal bleeding, fistula, or any life-threatening bleeding event within 6 months prior to enrollment. * Prior permanent discontinuation of PD-(L)1 and/or VEGF monoclonal antibody because of immune/anti-angiogenesis toxicities, or history of Grade ≥3 immune/anti-angiogenesis-related AEs * Known or suspected active autoimmune disease. * Patients with proteinuria at screening (Urine protein \>2+ at screening, or 2+ urine protein accompanied by 24-h urine protein ≥1 g/24 h). * History of myocardial infarction or stroke within 6 months prior to enrollment. * Subjects with clinically significant cardiovascular disease within 6 months prior to the first dose. * Pregnant and lactating women. * Known allergies to any excipient in the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) (Dose escalation) | at the end of Cycle 1 (each cycle is 28 days) | DLTs will be assessed during the dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria. |
| Maximum tolerated dose (MTD)and / or Recommended dose (RD) (Dose escalation) | Up to approximately 2 years | The MTD is defined as the dose of SIM0689 with an estimated toxicity rate closest to the target toxicity rate of 27%； RD stands for Recommended Dose, which will be selected based on the evaluation of all available pharmacokinetics, pharmacodynamic, efficacy, safety, and tolerability data |
| Objective Response Rate (ORR) (Dose expansion) | Up to approximately 2 years | ORR is the proportion of participants with complete response(CR)or partial response (PR) assessed according to RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event rate | up to approximately 2 years | The occurrence of all adverse events (AEs), evaluated by Common Terminology Criteria for Adverse Events (CTCAE) 6.0. |
| Pharmacokinetics: The area under the curve (AUC) | up to approximately 2 years | The area under the curve (AUC) of serum concentration of SIM0689 |
| Pharmacokinetics: Peak concentration (Cmax) | Up to approximately 2 years | Maximum observed concentration (Cmax) of SIM0689 |
| Pharmacokinetics: T1/2 | Up to approximately 2 years | Terminal half-life (T1/2) |
| Pharmacokinetics: Tmax | Up to approximately 2 years | Time to maximum concentration |
| Immunogenicity | Up to approximately 2 years | Titer of serum anti-SIM0689 antibodies |
Countries
China
Contacts
CONTACTTingbo Liang
CONTACTXueli Bai
Outcome results
None listed