A Study of HMPL-415S1 in Patients With Advanced Malignant Solid Tumors

A Multicenter, Open-Label Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-415S1 in Patients With Advanced Malignant Solid Tumor

The objective of this study is to evaluate the safety, tolerability and PK profile of HMPL-415S1 and determine MTD and/or RP2D in patients with advanced malignant solid tumor.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Solid Tumors
• Intervention / Treatment: Drug: HMPL-415S1

Detailed Description

This study is expected to enroll 36-81 patients, including 26-66 patients for dose escalation, additional 10-15 patients will be enrolled at the dose level of determined RP2D.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ronghua Zhang; Phone Number: +86 1526711056; Email: ronghuaz@hutch-med.com
• Study Contact Backup: Name: Yanbing Huang; Phone Number: +86 13724153286; Email: yanbingh@hutch-med.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Zhongshan Hospital Fudan University
      • Principal Investigator: Tianshu Liu
      • Contact: Tianshu Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All the following conditions must be met for enrollment:

1. Fully understand this study and voluntarily sign the ICF;
2. Dose escalation Patients with advanced malignant solid tumor confirmed by histopathology or cytology, who have failed, been intolerant or unavailable to, or have none standard treatment for various reasons; Dose expansion phase: Patients with advanced malignant solid tumor confirmed by histopathology or cytology, who have failed, been intolerant or unavailable to, or have none standard treatment for various reasons, carrying aberrant activating mutations in the KRAS pathway；
3. Presence of at least one measurable lesion (RECIST 1.1 criteria);
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 point;
5. Life expectancy ≥ 12 weeks as judged by the investigator;
6. Male of childbearing potential and their heterosexual partners of childbearing potential must agree to use effective methods of contraception.

Exclusion Criteria:

A patient may not participate in this study if any of the following conditions apply:

1. Patients who priorly received SHP2 inhibitors;
2. Receiving the approved systemic antitumor treatment within 4 weeks prior to the first dose, including: chemotreatment, targeted treatment, immunization treatment, biological treatment, etc. (wash-out for 2 weeks for hormone treatment or traditional chinese medicine and chinese patent medicine with clear antitumor indications);
3. Have been in the treatment period of other interventional clinical studies (including small molecule chemicals and large molecule antibodies) within 4 weeks prior to the first dose. If participating in a non-interventional clinical study (eg, epidemiological study), you can enroll in this study; if already in the survival follow-up period of an interventional clinical study, you can enroll in this study.
4. Major surgery or radical radiotreatment (except palliative radiotreatment for metastases to bone lesions) within 4 weeks prior to first dose.
5. Central nervous system (CNS) malignant tumor or known CNS metastasis;
6. Having multiple factors that affect the absorption, distribution, metabolism or excretion of orally administered drugs (such as inability to swallow drugs, frequent vomiting, chronic diarrhoea, etc.);
7. Any other disease, metabolic abnormality, physical examination abnormal, or clinically significant laboratory test abnormality that, in the judgment of the investigator, would compromise patient compliance or give reason to suspect that the patient has a disease or condition that would compromise the interpretation of study results or place the patient at high risk.

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: HMPL-415S1; HMPL-415S1 will be administered orally once daily in 28 days treatment cycles	Drug: HMPL-415S1; HMPL-415S1 will be supplied as 0.5 mg, 5 mg and 25 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety, tolerability, and determine the maximum tolerated dose (MTD) and/or RP2D of HMPL-415S1 as a single oral agent in advanced malignant solid tumor	Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period	from Cycle 0Day1 up to Cycle1Day28 (each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the pharmacokinetic (PK) profile of oral HMPL-415S1	Plasma peak concentration of HMPL-415S1 (Cmax).	from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).
AUCinf (Cycle 0 ) of HMPL-415S1	AUCinf: area under the concentration vs. time curve from zero to infinity after single (first)dose.	from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).
AUC(0-tlast) (Cycle 0 ) of HMPL-415S1	AUC from time zero to the last data point.	from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).
Objective Response Rate (ORR)	Percentage of patients with Complete Response(CR) or Partial Response(PR) as the best response evaluated in accordance with RECIST 1.1.	From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
Disease control rate (DCR)	the proportion of patients with CR or PR or stable disease (SD) as the best response, and the duration of SD needs to be ≥6 weeks.	From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
uration of response (DoR)	as the time from the first appearance of CR or PR to PD or death for any reason (whichever comes first), in the patients with objective response.	From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
Time to response (TTR)	the time from the first dose of HMPL-415S1 to the first objective response.	From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
Progression-free survival (PFS)	time from the first dose of study treatment to PD or death for any reason, whichever comes first.	From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
Overall survival (OS)	time from the first dose of study treatment to death for any reason.	From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Study Director: Bin Yang, Hutchison Medipharma Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2022-415-00CH1

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