SPH5030 Tablets in Subjects With Advanced Her2-positive Solid Tumors

A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of SPH5030 Tablets in Subjects With Advanced Her2-positive Solid Tumors

To evaluate the safety and tolerability of SPH5030 tablets in subjects with HER2-positive advanced solid tumors

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Advanced Solid Tumors
• Intervention / Treatment: Drug: SPH5030 tablets

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xingchen Wang; Phone Number: +8615811589825; Email: wangxc@sphchina.com

Study Locations

• China
  • Bengbu, China
    • Recruiting
    • The First Affiliated Hospital of Bengbu Medical University
    • Contact: Tingjing Yao
  • Neijiang, China
    • Recruiting
    • The second people's hospital of neijiang
    • Contact: Xujuan Wang
  • Tianjin, China
    • Recruiting
    • Tianjin Cancer Hospital Airport Hospital
    • Contact: Yehui Shi
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provincial Hospital
      • Contact: Yueyin Pan
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Binghe Xu
      • Principal Investigator: Binghe Xu
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yunxing Song; Phone Number: +86 17813230827; Email: songyx@sphchina.com
      • Principal Investigator: Yanxia Shi
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • Guangxi Cancer Hospital
      • Contact: Weimin Xie
  • Hebei
    • Shijiazhuang, Hebei, China
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Cuizhi Geng
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Qingyuan Zhang
  • Henan
    • Anyang, Henan, China
      • Recruiting
      • Anyang Cancer Hospital
      • Contact: Jing Sun
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Min Yan
  • Hubei
    • Xiangyang, Hubei, China
      • Recruiting
      • Xiangyang Central Hospital
      • Contact: Yuehua Wang
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Province Hospital
      • Contact: Jinhai tang
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • The First Affiliated Hospital of China Medical University
      • Contact: Fujian Liu
  • Shandong
    • Linyi, Shandong, China
      • Recruiting
      • LinYi Cancer Hospital
      • Contact: Jingfen Wang
  • Shanxi
    • Xi'an, Shanxi, China
      • Recruiting
      • The Second Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Shuqun Zhang
  • Tianjin
    • Tianjin, Tianjin, China, 300181
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital
      • Contact: Yunxing Song; Phone Number: +86 17813230827; Email: songyx@sphchina.com
      • Principal Investigator: Zhongsheng Tong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ECOG performance status of 0 to 1.
2. Life expectancy of more than 3 months.
3. At least one measurable lesion exists.(RECIST 1.1)
4. Histologically or cytologic confirmed HER2 positive metastatic solid tumor which failed prior standard treatment or have no standard treatment.

5. Required laboratory values including following parameters:

   ANC: ≥ 1.5 x 109/L Plt count: ≥ 90x 109/L Hb: ≥ 90 g/L TBIL: ≤ 1.5 x ULN, ALT and AST: ≤ 2.5 x ULN and creatine clearance rate: ULN or≥ 50 mL/min

6. Toxicity from previous antitumor therapy returned to baseline (except for residual hair loss effects) or CTCAE≤ class 1.
7. Blood pregnancy test was negative within 3 days prior to first dose.

Exclusion Criteria:

1. Subjects who have received the prescribed treatment at the prescribed time prior to first dosing.
2. Known active infection within 2 weeks prior to baseline.
3. Subjects with third space fluid that can not be controled by drainage or other methods.
4. Subjects with uncontrolled or severe cardiovascular disease.
5. Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.
6. Subjects with severe lung disease.
7. Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption.
8. Using a potent CYP3A4 or CYP2C8 inhibitor or inducer.
9. Steroid treatment for more than 50 days before, or in need of long-term use of steroids.
10. Uncured other tumors within 5 years.
11. Subjects with symptomatic CNS metastasis, pia meningeal metastasis, or spinal cord compression due to metastasis.
12. Evidence of chronic active hepatitis B or C
13. Uncontrolled systemic diseases, including hypertension that cannot be effectively controlled after treatment.
14. Receive any live or attenuated live vaccine within 28 days prior to baseline.
15. Evidence of severe allergies.
16. Evidence of alcohol or drug abuse.
17. Evidence of neurological or psychiatric disorders.

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: SPH5030 tablets; Subjects will take SPH5030 tablets orally on an empty stomach once or twice a day. Each subject will receive only one corresponding dose, and there were five dose groups: 50mg/ d, 100mg/ d, 200mg/ d, 300mg/ d and 400mg/ d.	Drug: SPH5030 tablets; SPH5030 tablets orally once or twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Measurement of DLT of SPH5030 in all subjects	Up to 24 days
Maximum tolerated dose（MTD）	Measurement of MTD of SPH5030 in all subjects	Up to 24 days
Number of patients with adverse events	Adverse event type, incidence, duration, correlation with study drug	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration (Cmax) of SPH 5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Time of maximum serum concentration (Tmax) SPH 5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Accumulation ratio of maximum serum concentration (Rac_Cmax) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Terminal rate constant(λz) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Half-life (t1/2) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Total clearance(CL) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Volume of distribution(Vz) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Percentage of area under the serum concentration-time curve (AUC) obtained by extrapolation (%AUCex) of SPH5030	To characterize the PK (Pharmacokinetics) of SPH 5030	Up to 2 years
Objective Response Rate (Investigator)	Determination of the Objective Response Rate of all patients by investigators	Up to 2 years
Duration of remission (DOR)	Time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review as per RECIST v1.1.	Up to 2 years
Disease control rate (DCR)	The proportion of patients with best confirmed RECIST response of CR, PR, or duration of SD.	Up to 2 years
Progression-free survival (PFS)	The interval between the dates of the first dose of trial treatment until first documentation of disease progression or death, whichever occurs first.	Up to 2 years
6-month Progression-free Survival (6mPFS)	Number of Patients Achieving 6-month Progression-free Survival	Up to 2 years

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Investigators: Principal Investigator: Binghe Xu, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Estimated): June 21, 2024
• Study Completion (Estimated): June 21, 2024

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SPH5030-101

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