Locally Advanced Solid Tumors
Conditions
Brief summary
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
Interventions
DRUGSIM0686
Administered intravenously
Sponsors
Jiangsu Simcere Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose escalation: Dose limited toxicity (DLT) | At the end of Cycle 1(each cycle is 21 days) | DLTs are assessed during the DLT observation period to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). |
| Dose escalation phase: Adverse Events (AEs) and Serious Adverse Events (SAEs) | The whole dose escalation phase，an average of 2 years | Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0. |
| Cohort expansion phase：Overall Response Rate (ORR) | The whole Cohort expansion phase，an average of 2 years | ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) by Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
Countries
China
Contacts
Primary ContactZhi Zhang
Outcome results
None listed