An Open Label, Multi-center, Phase I Clinical Study to Evaluate the Safety, Effectiveness and Pharmacokinetic Characteristics of SIM1803-1A in Patients With Locally Advanced/Metastatic Solid Tumors With NTRK, ROS1 or ALK Gene Fusion Mutations.

This research study is done to test the safety, effectiveness and pharmacokinetic characteristics of SIM1803-1A in patients with locally advanced/metastatic solid tumors with NTRK, ROS1 or ALK gene fusion mutations. The cancer must have a change in a particular gene (NTRK1, NTRK2, NTRK3, ROS1 or ALK). SIM1803-1A is a drug that blocks the actions of these NTRK/ ROS1 /ALK genes in cancer cells and can therefore be used to treat cancer.

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic Solid Tumors With NTRK, ROS1 or ALK Gene Fusion
• Intervention / Treatment: Drug: SIM1803-1A

• Study Type: Interventional
• Enrollment (Anticipated): 243
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: zhen zhou, MD; Phone Number: 021-22200000; Email: jenniferzhou1116@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Chest Hospital
    • Contact: zhen zhou, MD; Phone Number: 021-22200000; Email: jenniferzhou1116@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists；Proof of a malignancy harboring a NTRK、ROS1 or ALK fusion；Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 and a life expectancy of at least 3 month；Adequate hematologic, hepatic, and renal function；Signed informed consent form；

Exclusion Criteria:

• Any contraindications as listed in the local approved product information；Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible；Pregnancy or lactation；Clinically significant active cardiovascular disease or history of myocardial infarction；Participation in an investigational program with interventions outside of routine clinical practice；Prior treatment with other kinase inhibitor with tropomyosin receptor kinase inhibition；Active uncontrolled systemic bacterial, viral, or fungal infection；Current treatment with a strong CYP3A4 inhibitor or inducer；

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: adult patients_Dose 1	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 2	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 3	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 4	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 5	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 6	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 7	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Experimental: adult patients_Dose 8	Drug: SIM1803-1A; SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	Number of participants with adverse events	5 years
Severity of adverse events	Severity of adverse events	5 years
Maximum tolerated dose	Maximum tolerated dose	5 years
Recommended dose for dose expansion	Recommended dose for dose expansion	5 years
Maximum concentration of SIM1803-1A in plasma (Cmax)	Maximum concentration of SIM1803-1A in plasma (Cmax)	Predose and 0.25, 0.5, 1, 2, 4, 8，12，24and 48 hours after drug administration on Days 1 and 8 of Cycle 1（each cycle is 21 days）
Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted)	Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted)	Up to 1 day
Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC_fasted)	Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC_fasted)	Up to 3 days
Number of participants with treatment-emergent adverse events (TEAEs)	Number of participants with treatment-emergent adverse events (TEAEs)	Up to 24 weeks
Time to maximum concentration of SIM1803-1A in plasma (Tmax)	Time to maximum concentration of SIM1803-1A in plasma (Tmax)	Predose and 0.25, 0.5, 1, 2, 4, 8，12，24and 48 hours after drug administration on Days 1 and 8 of Cycle 1（each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Overall Response Rate (ORR)	Up to 60 months
Duration of Response (DOR)	Duration of Response (DOR)	Up to 60 months
progression-free survival（PFS）	progression-free survival（PFS）	Up to 60 months

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: shun lu, Ph.D, Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): January 30, 2024

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SIM1803-1A-NTRK-0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No