A Monotherapy in Subjects With Advanced Solid Tumors

NCT04221204 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 3D185-CN-001
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 2

Brief Summary

A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics Profiles, and Preliminary Efficacy of 3D185 Monotherapy in Subjects with Advanced Solid Tumors

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (2)

• Safety Evaluation: frequency and severity of AEs

  Evaluated based on the frequency and severity of AEs according to NCI CTCAE v4.03.

  24 months

• Tolerability Evaluation: frequency and severity of AEs

  based on the frequency and severity of AEs according to NCI CTCAE v4.03.

  24 Months

Secondary Outcomes (13)

• Efficacy evaluation: Complete Response

  24 months

• Pharmacokinetics (PK) evaluation: Cmax (mg/L)

  24 months

• PK evaluation: Tmax (minutes)

  24 months

• PK evaluation: AUC0-24 h, AUC0-96 h, AUC0-∞,

  24 months

• PK evaluation: t1/2

  24 months

Study Arms (1)

Open-Label, Dose-Escalation

EXPERIMENTAL

The starting dose in this dose-escalation study is 50 mg, and the preset 6 dose-escalation cohorts are 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg, respectively. This study adopts an i3+3 method for dose escalation. All subjects in each cohort will receive a single oral dose of 3D185, followed by a 7-day washout period (i.e. single-dose PK study period). Then, subjects will receive consecutive daily doses (Once daily \[QD\], 28 days/cycle) until disease progression, death, unacceptable toxicity, or withdraw of informed consent, whichever comes first

Drug: Highly selective FGFR1-3 inhibitor

Interventions

Highly selective FGFR1-3 inhibitor DRUG

All subjects in each cohort will receive a single oral dose of 3D185, followed by a 7-day washout period (i.e. single-dose PK study period). Then, subjects will receive consecutive daily doses (Once daily \[QD\], 28 days/cycle) until disease progression, death, unacceptable toxicity, or withdraw of informed consent, whichever comes first. The dose limiting toxicity (DLT) evaluation period includes the single-dose PK study period and the first treatment cycle (within 35 days after the first dose). The enrolled subjects will be sequentially assigned to the planned dose cohorts according to the protocol and receive 3D185 treatment to observe the occurrence of DLT.

Open-Label, Dose-Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be male or female and ≥ 18 years of age on the day of enrollment.
• Subjects must have a histological diagnosis of locally advanced or metastatic malignant solid tumors. Subjects must have failed or have been intolerant to established standard therapies, or standard therapies did not exist or were no longer effective for a given tumor type, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds.
• Subjects must have at least one evaluable lesion (according to RECIST 1.1, see Appendix 1);
• ECOG Performance Status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Subjects must have normal levels of total serum calcium and total phosphate.
• Subjects must have adequate organ and bone marrow function (no hematopoietic growth factor, blood transfusion, or platelet therapy within 1 week before the first dose):
• CBC: neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL.
• Liver function: total bilirubin ≤ 1.5 × ULN; ALT/AST ≤ 2.5 × ULN without liver metastasis; ALT/AST ≤ 5 × ULN with liver metastasis;
• Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (for patients undergoing anticoagulant therapy. The Investigator will judge that the INR and APTT are within a safe and effective treatment range).
• Renal function: serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min/1.73 m2 in the condition of creatinine level \> ULN; urine protein qualitative ≤ 1 + (if ≥ 2+, 24 hours of urine protein test is required, if 24 hours urine protein \<1 g, then allowed to enroll);
• Adequate cardiac function left ventricular ejection fraction (LVEF) \> 50% for 2 dimensional cardiac ultrasound;
• Subjects must have signed and dated an IRB/IEC approved written informed consent form that under regulatory and institutional guidelines, and this must be obtained before the performance of any protocol-related procedures.

You may not qualify if:

• Subjects who meet any of the following criteria should be excluded from the study:
• Subjects who received other investigational products or devices in other clinical trials within 4 weeks before the first dose;
• Subjects who received anti-tumor therapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs) within 4 weeks before the first dose, including but not limited to chemotherapy, radiotherapy (palliative radiotherapy is completed at least 2 weeks before the first dose can enroll), targeted therapy or immunotherapy.
• Note: Mitomycin and nitrosourea have been treated within 6 weeks after the last dose; oral fluorouracil such as tegafur and capecitabine has been treated within 2 weeks after the last dose.
• Subjects who previously received FGFR1-3 specific inhibitor therapy.
• Subjects who have previous toxicity of anti-tumor therapy that has not been returned to level 0 or 1. (Alopecia, chemotherapy-induced peripheral neurotoxicity and ototoxicity ≤ Grade 2 can enroll);
• Subjects who received a CYP3A4 and/or CYP2C8 strong inhibitor or a CYP3A4 strong inducer (see Appendix 6) within 7 days prior to the first dose, and need to continue using these drugs;
• Subjects who have any of the following eye diseases/conditions:
• History of retinal pigment epithelial detachment (RPED);
• History of laser treatment or intraocular injection for macular degeneration;
• History of dry or wet age-related macular degeneration;
• History of retinal vein occlusion (RVO);
• History of retinal degenerative diseases;
• History of chorioretinal lesions;
• Subjects who received clinical intervention for biliary obstruction 14 days prior to the first dose or the Investigator judges that the symptoms had not resolved or required anti-infective treatment.

Sponsors & Collaborators

• 3D Medicines (Beijing) Co., Ltd.: lead

Study Sites (2)

Sarcoma Oncolog Research Center

Santa Monica, California, 90403, United States

Location

Shanghai East Hospital

Shanghai, China

Location

Study Officials

• Di Zhu

  3D Medicines (Beijing) Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: sequential assignment The starting dose in this dose-escalation study is 50 mg, and the preset 6 dose-escalation cohorts are 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg, respectively.

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: January 9, 2020
• Study Start: September 1, 2019
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); US (1)