Clinical trial NCT05088070: Clinical Study of SPH3348 Tablets, a C-Met Inhibitor, in Patients with Advanced Solid Tumors
Official title: Phase I Clinical Study of SPH3348 Tablets, a C-Met Inhibitor, in Patients with Advanced Solid Tumors with C-Met Abnormalities
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-10-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 24 days
measure: Maximum tolerated dose (MTD)
timeFrame: 24 days
Secondary outcomes:
measure: Maximum serum concentration (Cmax) of SPH 3348.
timeFrame: 24 days
measure: Time of maximum serum concentration (Tmax) SPH 3348.
timeFrame: 24 days
measure: Area under the concentration-time curve (AUC) of SPH 3348.
timeFrame: 24 days
measure: Half-life (t1/2) of SPH 3348.
timeFrame: 24 days
measure: Objective Response Rate (ORR)
timeFrame: 24 days
measure: Disease control rate (DCR)
timeFrame: 24 days
measure: Duration of remission (DOR)
timeFrame: 24 days
measure: Progression-free survival (PFS)
timeFrame: 24 days
measure: Biomarker expression level
timeFrame: 24 days
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affliated Hospital of Bengbu Medical College
state: Anhui
Study officials:
affiliation: The First Affliated Hospital of Bengbu Medical College
name: Zishu Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affliated Hospital of Bengbu Medical College
name: Huan Zhou
role: PRINCIPAL_INVESTIGATOR
References: