Clinical Study of SPH3348 Tablets, a c-Met Inhibitor, in Patients With Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05088070
• Other study ID #: SPH3348-101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: August 2023
• Source: Shanghai Pharmaceuticals Holding Co., Ltd
• Contact: Zishu Wang
• Phone: 13955254185
• Email: wzshahbb[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 231
• Est. completion date: December 30, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
China	The First Affliated Hospital of Bengbu Medical College	Bengbu	Anhui

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Pharmaceuticals Holding Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Incidence of DLT in all subjects.	24 days
Primary	Maximum tolerated dose (MTD)	Measurement of MTD in all subjects.	24 days
Secondary	Maximum serum concentration (Cmax) of SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Secondary	Time of maximum serum concentration (Tmax) SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Secondary	Area under the concentration-time curve (AUC) of SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Secondary	Half-life (t1/2) of SPH 3348.	To characterize the PK (Pharmacokinetics) of SPH 3348.	24 days
Secondary	Objective Response Rate (ORR)	Measurement of ORR in all subjects.	24 days
Secondary	Disease control rate (DCR)	Measurement of DCR in all subjects.	24 days
Secondary	Duration of remission (DOR)	Measurement of DOR in all subjects.	24 days
Secondary	Progression-free survival (PFS)	Measurement of PFS in all subjects.	24 days
Secondary	Biomarker expression level	Evaluate the level of hepatocyte growth factor(HGF).	24 days