Evaluating HMPL-415S1 for 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

This study is testing a new treatment called HMPL-415S1 to see if it is safe and how well it works for people with advanced solid tumors who haven't responded to other treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 81 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hutchmed (industry)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05886374 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety, tolerability, and pharmacokinetics of HMPL-415S1 in patients with advanced malignant solid tumors. It will enroll between 36 to 81 patients, focusing on dose escalation and determining the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Participants must have tumors confirmed by histopathology or cytology and have previously failed or been intolerant to standard treatments. The study will also evaluate patients with specific mutations in the KRAS pathway during the dose expansion phase.

Who should consider this trial

Good fit: Ideal candidates are patients with advanced malignant solid tumors who have failed or been intolerant to standard treatments and have measurable lesions.

Not a fit: Patients with early-stage tumors or those who have not yet received standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced malignant solid tumors who have limited treatment choices.

How similar studies have performed: While this approach is being explored in this specific context, similar studies targeting advanced solid tumors have shown promise in the past.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital Fudan University — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Ronghua Zhang

Conditions: Advanced Malignant Solid Tumors