A Study of QLS31905 Combination Chemotherapy as First-Line Treatment in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study aims to evaluate the efficacy and safety of QLS31905 plus chemotherapy in patients with Claudin18.2-positive advanced solid tumors.

Official Title
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A Phase IB/II Clinical Study to Assess the Efficacy and Safety of QLS31905 in Combination With Chemotherapy as First-line Treatment in Patients With Claudin 18.2 (CLDN18.2) Positive Advanced Malignant Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: QLS31905
* Drug: Nab paclitaxel
* Drug: Gemcitabine
* Drug: Oxaliplatin
* Drug: Capecitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily participate in the study and sign the informed consent form; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; Expected survival time ≥ 3 months; Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors; No prior systemic anti-tumor treatment for locally advanced unresectable or metastatic disease; Tumor tissue samples determined to have moderate-to-high Claudin18.2 expression by immunohistochemistry (IHC); At least one measurable lesion per RECIST v1.1; Patients with adequate cardiac, liver, renal function, etc. Exclusion Criteria: History of malignancies other than the target cancer within 5 years prior to the first dose of the investigational product ; Underwent major organ surgery (excluding needle biopsy) or had significant trauma within 28 days prior to enrollment, or requires elective surgery during the study; Known central nervous system metastases; Patients with hepatitis B; patients with hepatitis C; patients who test positive for syphilis, or patients with a known history of HIV or positive HIV screening test; Patients with a known history of psychoactive drug abuse, alcohol abuse, or substance abuse; Patients with added risks associated with the study or may interfere with the interpretation of study results as determined by the investigator, or deemed unsuitable by the investigator and/or sponsor.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)<br>Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine. | Drug: QLS31905<br>* Administered as an intravenous infusion.<br>Drug: Nab paclitaxel<br>* 125 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.<br>Drug: Gemcitabine<br>* 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.<br>|
| Experimental: QLS31905 + oxaliplatin + capecitabine (Part B)<br>In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine. | Drug: QLS31905<br>* Administered as an intravenous infusion.<br>Drug: Oxaliplatin<br>* 85 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.<br>Drug: Capecitabine<br>* 1000 mg/m2, oral, bid, D1-D7,D15-D21, up to 6 cycles.<br>|
| Experimental: QLS31905 + gemcitabine+cisplatin(Part B)<br>In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer. | Drug: QLS31905<br>* Administered as an intravenous infusion.<br>Drug: Gemcitabine<br>* 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.<br>Drug: Cisplatin<br>* 25 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) (Part A) | As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort. | Approximately 12 months | 
| Phase 2 Recommended Dose（RP2D)(Part A) | Monitor for MTD, and minimal efficacious dose by monitoring responses at different dose levels. | Approximately 12 months | 
| Objective response rate (ORR)(Part B) | ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1. | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by Adverse Events (AEs) | An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom,or disease (new or exacerbated) temporally associated with the use of a medicinal product. | Approximately 12 months | 
| Safety assessed by incidence of serious adverse events (SAE) | Adverse Event (AE) is considered serious if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect,hospitalization, or medically important event. | Approximately 12 months | 
| Number of participants with laboratory value abnormalities and/or adverse events (AEs) | Number of participants with potentially clinically significant laboratory values. | Approximately 12 months | 
| Progression Free Survival(PFS) | PFS is defined as the duration from the subject's first dose of the investigational product to the first imaging confirmation of progressive disease per RECIST 1.1 by investigator evaluation or death due to any cause (whichever occurs first). | Approximately 12 months | 
| Duration Of Response (DOR) | DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or death due to any cause (whichever occurs first). | Approximately 12 months | 
| Overall Survival (OS) | OS is defined as the duration from the first dose of the investigational product to the time point when death occurs due to any cause. | Approximately 12 months | 
| Pharmacokinetics(PK) of QLS31905: Maximum concentration (Cmax) | Cmax will be derived from the PK serum samples collected. | Approximately 12 months | 
| PK of QLS31905: Time of the maximum concentration (Tmax) | Tmax will be derived from the PK serum samples collected. | Approximately 12 months | 
| PK of QLS31905: Terminal elimination half-life (T1/2) | T1/2 will be derived from the PK serum samples collected. | Approximately 12 months | 
| PK of QLS31905: Clearance (CL) | CL will be derived from the PK serum samples collected. | Approximately 12 months | 
| PK of QLS31905: Apparent volume of distribution during the terminal phase (Vz) | Vz will be derived from the PK serum samples collected. | Approximately 12 months | 
| Number of anti-drug antibody (ADA) Positive Participants | Immunogenicity will be measured by the number of participants that are ADA positive. | Approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QLS31905, CLDN18.2