A Phase I Study of SIM0686 in Participants With Locally Advanced/Metastatic Solid Tumors

A Phase I First-in-Human, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0686 in Adult Participants With Locally Advanced/Metastatic Solid Tumors

This is an open-label, multicenter phase 1 study to evaluate the safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0686 in Adult Participants with Locally Advanced/Metastatic Solid Tumors

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 (RECIST v1.1);
• 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 6 months before first administration for evaluation of FGFR2b expression levels

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.

• Participant has symptomatic central nervous system (CNS) metastases, or CNS metastases requiring CNS-directed local therapy (such as radiotherapy or surgery) or corticosteroids therapy within 2 weeks of first dose of study treatment.

• Active or chronic corneal disorder, history of corneal transplantation, keratitis, keratoconjunctivitis, keratopathy, keratoconus, corneal abrasion, inflammation or ulceration, other active ocular conditions and any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.

• 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.

• Participant has not recovered (i.e., to Grade 1 or to baseline) from previous anticancer therapy-induced AEs.

• Has received prior therapies within the following time frames prior to the first dose of study treatment:

  1. Previous cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors) within 2 weeks.
  2. Anti-cancer antibody, immune checkpoint inhibitor or ADC within 5 half-lives or 4 weeks (whichever is shorter).
  3. Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks.
  4. Radiation therapy within 4 weeks.

• Prior exposure to topoisomerase I inhibitor (TOP1i)-based antibody-drug conjugate (ADC) therapies or FGFR2b-targeted ADC therapies.

• Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).

• Active or chronic hepatitis B or hepatitis C infection;