Evaluating QLH11906 for advanced solid tumors with MAPK alterations

A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Oral Pan-RAF Inhibitor QLH11906 in Subjects With Advanced Solid Tumors Harboring MAPK Pathway Alterations.

This study is testing a new drug called QLH11906 to see if it is safe and how well it works for people with advanced solid tumors that have specific genetic changes.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Qilu Pharmaceutical Co., Ltd. (industry)
• Locations: 1 site (Shandong)
• Trial ID: NCT05488821 on ClinicalTrials.gov

What this trial studies

This open-label phase 1 clinical study aims to assess the safety and tolerability of varying doses of QLH11906 monotherapy in patients with relapsed or refractory advanced solid tumors that have abnormal MAPK pathway alterations. The study will determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) if MTD cannot be established, as well as the Recommended Phase II Dose (RP2D) for future studies. Participants will be closely monitored for any adverse effects and overall response to the treatment.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced solid tumors that have confirmed MAPK pathway alterations and meet specific health criteria.

Not a fit: Patients who have recently undergone systemic anticancer therapy or radical radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that have specific genetic alterations.

How similar studies have performed: While this approach is novel, similar studies targeting MAPK pathway alterations have shown promise in other contexts.

Eligibility criteria

Inclusion Criteria:

1. The subjects participated voluntarily, signed the informed consent, and were able to abide by the research procedures.
2. Subjects with advanced (metastatic or unresectable) solid tumors with histologically confirmed MAPK signaling pathway alteration.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
4. Subjects are able to swallow and retain oral medication without any clinically significant gastrointestinal abnormalities that alter absorption.
5. Subjects (including women and men) agree to use effective contraception for contraception from the time of signing the informed consent form to 180 days after the last use of the study drug. Female subjects of childbearing age cannot be pregnant or breastfeeding.

Exclusion Criteria:

1. Subjects received systemic anticancer therapy within 2 weeks prior to the first dose.
2. Subjects received radical radiotherapy within 4 weeks before the first administration, or received local palliative radiotherapy for bone metastases within 1 week.
3. Subjects who have received inhibitors or inducers of CYP3A4 within 1 week before the first dose; or within 5 half-lives of the drug; or subjects who need to continue to receive these drugs during the study period.
4. Active bacterial, fungal, or viral infection requiring systemic therapy within 1 week prior to the first dose.
5. Subjects with symptomatic central nervous system (CNS) metastases and/or cancerous meningitis.
6. Cardiovascular and cerebrovascular diseases with clinical significance.
7. Clinically uncontrollable serous effusion (eg, pleural effusion that cannot be controlled by drainage or other methods).
8. Active gastrointestinal disease or other conditions that significantly interfere with drug absorption.
9. Known immediate or delayed hypersensitivity reactions or idiosyncratic reactions to the investigational treatment-related chemotherapeutic drugs and their excipients.
10. Human immunodeficiency virus (HIV) positive test result and Treponema pallidum antibody positive.
11. Hepatitis B virus surface antigen (HBsAg) positive and viral deoxyribonucleic acid (HBV DNA) \> 2000 IU/ml or 104 copies/ml (only the centers that can perform qualitative examination, the HBV DNA test result is positive or high detection limit); hepatitis C virus antibody positive and viral ribonucleic acid (HCV RNA) positive.
12. Other malignant tumors occurred within 2 years before study enrollment. (Except: Bowen's disease; cured basal cell or squamous cell skin cancer; prostate cancer with a Gleason score of 6; treated cervical carcinoma in situ.)
13. Pregnant or lactating women.
14. Any pre-existing serious or unstable disease (except for the above-mentioned malignant tumors), mental disease or any disease or medical condition that the investigator considers may interfere with the subject's safety, obtaining informed consent, or complying with research procedures.
15. Concurrent participation in other clinical trials using experimental therapies.

Where this trial is running

Shandong

• Shandong Cancer Hospital — Shandong, China (RECRUITING)

Study contacts

• Study coordinator: Lianghua Fang

Conditions: Advanced Solid Tumors Harboring MAPK Pathway Alterations