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

July 19, 2023 updated by: Hutchmed

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
81

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Time Frame: from Cycle 0Day1 up to Cycle1Day28 (each cycle is 28 days).
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To investigate the pharmacokinetic (PK) profile of oral HMPL-415S1
Time Frame: from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).
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
Time Frame: from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).
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
Time Frame: from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).
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)
Time Frame: From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
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)
Time Frame: From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
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)
Time Frame: From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
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)
Time Frame: From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
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 Frame: From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
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 Frame: From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years).
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hutchmed

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Bin Yang, Hutchison Medipharma Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 6, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 2, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 19, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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