A Phase I Study of SIM0609 in Adult Participants With Locally Advanced/Metastatic Solid Tumors

Official title

A Phase I First-in-Human, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0609 in Adult Participants With Locally Advanced/Metastatic Solid Tumors

Overview

This is an open-label,multicenter phase I study to evaluate the safety,Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0609 in Adult Participants with Locally Advanced/Metastatic Solid Tumors

Interventions

• Drug SIM0609 for injection
  Multiple dose levels of SIM0609 will be explored in dose escalation
• Drug dose expansion of SIM0609 in CRC
  1\~3 dose levels of SIM0609 will be explored in dose expansion to evaluate the preliminary anti-tumor activity of SIM0609 in colorectal carcinoma (CRC)
• Drug dose expansion of SIM0609 in GC/GEJC cohort
  1\~3 dose levels of SIM0609 will be explored in dose expansion in GC/GEJC cohort
• Drug dose expansion of SIM0609 in PDAC cohort
  1\~3 dose levels of SIM0609 will be explored in dose expansion in PDAC cohort
• Drug dose expansion of SIM0609 in positive other solid tumors
  1\~3 dose levels of SIM0609 will be explored in positive other solid tumors cohort

Primary outcome measures

• Dose escalation:Dose -limiting toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 21/28days)]
• Dose escalation:Safety and Tolerability [Time frame: 2 years]
• Dose escalation: Objective response rate(ORR) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Voluntary participation and signature of informed consent form;
• At least 18 years old, male or female;
• Participants with histologically and/or cytologically confirmed locally advanced/metastatic solid tumors;
• Participants should have at least one evaluable or measurable tumor lesion;
• Participants have failed the standard of therapy in the locally advanced/metastatic setting;
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1;
• Expected survival ≥12 weeks;
• Adequate organ and bone marrow function;
• Availability of archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue, or fresh biopsies within 28 days before first administration, is mandatory

Exclusion criteria

• Active second primary malignancies within the previous 2 years except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence;
• Symptomatic central nervous system (CNS) metastases or CNS metastases requiring CNS-directed local therapy or corticosteroid treatment that occurred within 2 weeks prior to the first administration of the investigational treatment;
• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging screening;
• Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study ;
• Any active infections requiring systemic therapy within 2 weeks prior to the initiation of the study treatment;
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment;
• Not recovered from previous anticancer therapy-induced AEs(Adverse Events);
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of study treatment;
• Received prior therapies within the following time frames prior to the first dose of study treatment:

• Previous cytotoxic therapy, anticancer targeted small molecules within 2 weeks.
• Anti-cancer antibody, immune checkpoint inhibitor or ADC within 5 half-lives or 4 weeks (whichever is shorter).
• Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks.
• Radiation therapy within 4 weeks.
• Prior exposure to topoisomerase I inhibitor (TOP1i)-based antibody drug conjugate (ADC) therapies or CDH17-targeted ADC therapies.
• Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.
• Administration of below medications ≤14 days prior to the first dose of study treatment.

• Strong or moderate CYP3A4 inducers/inhibitors;
• Drugs with known risk of Torsades de Pointes(TdP);
• Drugs that may prolong the QT interval;
• Major surgery within 2 weeks of receiving the first dose of study treatment;
• Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome ;
• Active or chronic hepatitis B or hepatitis C infection;
• Participants with clinically significant cardiovascular diseases;
• History of allogeneic organ transplantation or graft-versus-host disease;
• History of hypersensitivity to active or inactive excipients of SIM0609 or drugs with a similar chemical structure or class to SIM0609;
• Pregnant or nursing (lactating) women;
• Male participants with female partners of reproductive potential, unless they are using highly effective contraceptive methods from signing of informed consent to 180 days after the last dose of study treatment;
• Presence of any other condition that may increase the risk associate with study participant or may interfere with the interpretation of study results, and, in the opinion of the Investigator, would make the participant inappropriate for entry into the study.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

• Beijing Cancer Hospital — Beijing
• Jiangsu Province Hospital — Nanjing
• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai
• Zhongshan Hospital，Fudan University — Shanghai
• Tianjin Cancer Hospital — Tianjin
• Hubei Cancer Hospital — Wuhan

Identifiers

NCT: NCT07265921 · SIM0609-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗