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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: QLS31905; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 115
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lin Shen, M.D; Phone Number: 010-881965671; Email: linshenpku@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B); 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; Administered as an intravenous infusion.; Drug: Nab paclitaxel; 125 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.; Drug: Gemcitabine; 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.
Experimental: QLS31905 + oxaliplatin + capecitabine (Part B); 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; Administered as an intravenous infusion.; Drug: Oxaliplatin; 85 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.; Drug: Capecitabine; 1000 mg/m2, oral, bid, D1-D7,D15-D21, up to 6 cycles.
Experimental: QLS31905 + gemcitabine+cisplatin(Part B); 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; Administered as an intravenous infusion.; Drug: Gemcitabine; 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.; Drug: Cisplatin; 25 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: August 30, 2023
• First Submitted That Met QC Criteria: September 10, 2023
• First Posted (Actual): September 18, 2023

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 10, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: CLDN18.2; QLS31905
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Capecitabine; Oxaliplatin; Gemcitabine
• Other Study ID Numbers: QLS31905-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No