Clinical Study of SPH3348 Tablets, a C-Met Inhibitor, in Patients with Advanced Solid Tumors

Phase I Clinical Study of SPH3348 Tablets, a C-Met Inhibitor, in Patients with Advanced Solid Tumors with C-Met Abnormalities

This is a phase 1 clinical trial of SPH3348 tablets, a c-Met inhibitor, in patients with advanced solid tumors with c-Met abnormalities. A modified 3 + 3 design was adopted in patients with advanced solid tumors with c-Met abnormalities, with a total of 6 dose groups, in which accelerated dose escalation was adopted for the lowest dose group, and 3 + 3 dose escalation was adopted from the second dose group. The primary objective was to evaluate the safety and tolerability of SPH3348 tablets in patients with advanced solid tumors with c-Met abnormalities.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: SPH 3348; Drug: SPH 3348; Drug: SPH 3348; Drug: SPH 3348; Drug: SPH 3348; Drug: SPH 3348

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • Recruiting
      • The First Affliated Hospital of Bengbu Medical College
      • Principal Investigator: Zishu Wang
      • Contact: Huan Zhou
      • Principal Investigator: Huan Zhou

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with advanced solid tumors with c-Met abnormalities who have failed standard of care or are not eligible for standard therapy currently
2. ECOG score of 0 or 1.
3. Patients must have measurable lesion that can be assessed by imaging per RECIST 1.1 criteria.
4. Expected survival > 12 weeks.
5. Patients must have adequate organ function
6. Patients must give informed consent to the study and sign the informed consent form prior to the trial.

Exclusion Criteria:

1. Received anti-tumor therapies, including but not limited to chemotherapy, biotherapy, radiotherapy, targeted therapy, etc., within 4 weeks prior to the first dose of study drug; received nitrosoureas or mitomycin C within 6 weeks prior to the start of study drug.
2. Received small molecule tyrosine kinase inhibitors within 2 weeks prior to the first dose.
3. Received strong CYP3A4 inducers or inhibitors or CYP3A4 substrates with narrow therapeutic windows within 2 weeks prior to the start of study drug.
4. Patients with active hepatitis B (hepatitis B surface antigen (HBsAg) positive) or hepatitis C (HCV).
5. Toxicities caused by prior treatments have not recovered to CTCAE Grade ≤ 1 or having ≥Grade 2 peripheral neuropathy, except for alopecia and other events judged as tolerable by the investigator.
6. Known allergy to any component of the reference drug.
7. Known drug or alcohol dependence.
8. Received surgical treatment including surgical and interventional procedures within 4 weeks prior to the start of study drug.
9. Patients with brain metastases.
10. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or evidence of any clinically active interstitial lung disease.
11. Acute bacterial, viral, or fungal infection requiring systemic therapy or unexplained fever (temperature > 38.5 °C) during screening, prior to the first dose.
12. Neurological and psychiatric patients with obvious poor compliance.
13. Any of the following within 6 months prior to signing of informed consent form: uncontrolled congestive cardiac failure, severe or unstable angina pectoris, myocardial infarction, stroke, coronary/peripheral artery bypass surgery, pulmonary embolism.
14. Arrhythmia uncontrolled by medication or sustained QTcB prolongation.
15. Hypertension uncontrolled by medication
16. Participated in other drug clinical studies within 28 days prior to the first dose of study drug.
17. Women who are pregnant or in lactation period or women/men with childbearing plans.
18. Patients who cannot take oral medication, or have previous surgical history or serious gastrointestinal diseases such as dysphagia, active gastric ulcer, which may impair the absorption of the study drug in the investigator's opinion.
19. Other prior or current concomitant malignancies.
20. Patients who are ineligible to participate in this trial for any reason judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SPH 3348 tablets; 6 different dosage group of SPH 3348 will be assigned with 16mg, 40mg, 80mg, 160mg, 240mg and 320mg respectively.

Drug: SPH 3348; 2 tablets of 8mg SPH3348 will be orally administered once a day with empty stomach; Drug: SPH 3348; 1 tablet of 40mg SPH3348 will be orally administered once a day with empty stomach; Drug: SPH 3348; 2 tablets of 40mg SPH3348 will be orally administered once a day with empty stomach; Drug: SPH 3348; 4 tablets of 40mg SPH3348 will be orally administered once a day with empty stomach; Drug: SPH 3348; 6 tablets of 40mg SPH3348 will be orally administered once a day with empty stomach; Drug: SPH 3348; 8 tablets of 40mg SPH3348 will be orally administered once a day with empty stomach

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Incidence of DLT in all subjects.	24 days
Maximum tolerated dose (MTD)	Measurement of MTD in all subjects.	24 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration (Cmax) of SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Time of maximum serum concentration (Tmax) SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Area under the concentration-time curve (AUC) of SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Half-life (t1/2) of SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Objective Response Rate (ORR)	Measurement of ORR in all subjects.	24 days
Disease control rate (DCR)	Measurement of DCR in all subjects.	24 days
Duration of remission (DOR)	Measurement of DOR in all subjects.	24 days
Progression-free survival (PFS)	Measurement of PFS in all subjects.	24 days
Biomarker expression level	Evaluate the level of hepatocyte growth factor(HGF).	24 days

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Investigators: Principal Investigator: Zishu Wang, The First Affliated Hospital of Bengbu Medical College; Principal Investigator: Huan Zhou, The First Affliated Hospital of Bengbu Medical College

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Actual): July 30, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 30, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SPH3348-101

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
• product manufactured in and exported from the U.S.: No