Phase 1 testing of SIM0686 for locally advanced or 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 trial will try SIM0686 in adults with locally advanced or metastatic solid tumors to see if it is safe, how the body processes it, and whether it shows early signs of tumor control.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. (industry)
• Drugs / interventions: Radiation
• Locations: 10 sites (Beijing, Beijing Municipality and 9 other locations)
• Trial ID: NCT07050459 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter Phase 1 study administers SIM0686 to adults with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have exhausted standard therapies. The primary focus is on safety, tolerability, and pharmacokinetics, with preliminary antitumor activity measured by RECIST v1.1 as a secondary outcome. Eligible participants must have ECOG 0–1, at least one measurable lesion, adequate organ and marrow function, and available archival or fresh tumor tissue for FGFR2b expression testing. The trial is being conducted at several cancer centers in China and uses dose-escalation methods typical of first-in-human/early-phase oncology studies.

Who should consider this trial

Good fit: Adults with histologically confirmed locally advanced or metastatic solid tumors who have failed standard therapies, have ECOG 0–1, measurable disease, adequate organ function, and available tumor tissue for FGFR2b testing are the intended candidates.

Not a fit: Patients with poor performance status (ECOG >1), inadequate organ function, active recent second primary cancers, or tumors lacking FGFR2b expression may not receive benefit from this investigational treatment.

Why it matters

Potential benefit: If successful, SIM0686 could become a new treatment option that helps control tumor growth for patients whose advanced solid tumors express FGFR2b.

How similar studies have performed: FGFR-targeted therapies have shown responses in select tumor types, so the approach has precedent, but SIM0686 itself is at an early clinical stage and its efficacy remains unproven.

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 (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;

Where this trial is running

Beijing, Beijing Municipality and 9 other locations

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (NOT_YET_RECRUITING)
• Harbin Medical University Cancer Hospital — Haerbin, Heilongjiang, China (NOT_YET_RECRUITING)
• The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital — Zhengzhou, Henan, China (NOT_YET_RECRUITING)
• Hunan Cancer Hospital — Changsha, Hunan, China (NOT_YET_RECRUITING)
• Nanjing Tianyinshan Hospital — Nanjing, Jiangsu, China (RECRUITING)
• Cancer Hospital of Shandong First Medical University（Shandong Cancer Hospital&Institute） — Jinan, Shandong, China (NOT_YET_RECRUITING)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (NOT_YET_RECRUITING)
• Shanghai Gobroad Cancer Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)
• Sichuan Cancer Hospital — Chengdu, Sichuan, China (RECRUITING)
• Tianjin Cancer Hospital — Tianjin, Tianjin Municipality, China (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Zhi Zhang

Conditions: Locally Advanced Solid Tumors