A Study of SIM0689 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

Official title

Phase I First-in-Human, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0689 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

Overview

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

• Drug SIM0689 for Injection
  SIM0689 for Injection is a Programmed Cell Death Protein 1(PD1) / Vascular Endothelial Growth Factor (VEGF) bispecific antibody.

Primary outcome measures

• Dose-limiting toxicity (DLT) (Dose escalation) [Time frame: at the end of Cycle 1 (each cycle is 28 days)]
• Maximum tolerated dose (MTD)and / or Recommended dose (RD) (Dose escalation) [Time frame: Up to approximately 2 years]
• Objective Response Rate (ORR) (Dose expansion) [Time frame: Up to approximately 2 years]

Secondary outcome measures (8)

• Adverse event rate [Time frame: up to approximately 2 years]
• Pharmacokinetics: The area under the curve (AUC) [Time frame: up to approximately 2 years]
• Pharmacokinetics: Peak concentration (Cmax) [Time frame: Up to approximately 2 years]
• Pharmacokinetics: T1/2 [Time frame: Up to approximately 2 years]
• Pharmacokinetics: Tmax [Time frame: Up to approximately 2 years]
• Immunogenicity [Time frame: Up to approximately 2 years]
• Immunogenicity [Time frame: Up to approximately 2 years]
• Immunogenicity [Time frame: Up to approximately 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

• Fujian Cancer Hospital — Fuzhou
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• Hunan Cancer Hospital — Changsha
• The First Hospital of China Medical University — Shenyang
• Cancer Hospital of Shandong First Medical University — Jinan
• The First Affiliated Hospital, Zhejiang University school of Medicine — Hangzhou

Identifiers

NCT: NCT07660432 · SIM0689-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗