Study of QLS31905 and/or QL1706 Combination With Chemotherapy in the Advanced Malignant Solid Tumors

A Phase II Clinical Study to Evaluate the Efficacy and Safety of QLS31905 and/or QL1706 Combination Chemotherapy for the Treatment of CLDN18.2-Positive Advanced Malignant Solid Tumors

This study aims to evaluate the efficacy and safety of QLS31905 and/or QL1706 plus chemotherapy in patients with Claudin18.2-positive advanced solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: QLS31905; Drug: Oxaliplatin; Drug: Capecitabine; Drug: QL1706; Drug: Gemcitabine; Drug: Cisplatin; Drug: Chemotherapy drug

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
      • Contact: Lin Shen, M.D; Phone Number: 010-881965671; Email: linshenpku@163.com

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 be positive for Claudin18.2 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

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QLS31905 + oxaliplatin + capecitabine; Gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at doses determined by the phase I study in combination with oxaliplatin and capecitabine.	Drug: QLS31905; Administered as an intravenous infusion.; Drug: Oxaliplatin; 130 mg/m2, intravenous infusion, D1, up to 8 cycles.; Drug: Capecitabine; 1000 mg/m2, oral, bid, D1-D14
Experimental: QL1706 + oxaliplatin + capecitabine; Gastric/gastroesophageal junction cancer participants will be treated with QL1706 in combination with oxaliplatin and capecitabine.	Drug: Oxaliplatin; 130 mg/m2, intravenous infusion, D1, up to 8 cycles.; Drug: Capecitabine; 1000 mg/m2, oral, bid, D1-D14; Drug: QL1706; 5 mg/kg, intravenous infusion,D1
Experimental: QLS31905 + oxaliplatin + capecitabine + QL1706; Gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at doses determined by the phase I study in combination with oxaliplatin and capecitabine+ QL1706.	Drug: QLS31905; Administered as an intravenous infusion.; Drug: Oxaliplatin; 130 mg/m2, intravenous infusion, D1, up to 8 cycles.; Drug: Capecitabine; 1000 mg/m2, oral, bid, D1-D14; Drug: QL1706; 5 mg/kg, intravenous infusion,D1
Experimental: QLS31905 + gemcitabine+cisplatin; Biliary tract cancer will be treated with QLS31905 at doses determined by the phase I study in combination with gemcitabine and cisplatin.	Drug: QLS31905; Administered as an intravenous infusion.; Drug: Gemcitabine; 1000 mg/m2 administered as IV infusion on D1/D8 of each cycle.; Drug: Cisplatin; 25 mg/m2, intravenous infusion, D1/D8, up to 8 cycles.
Experimental: QL1706 + gemcitabine+cisplatin; Biliary tract cancer will be treated with QL1706 in combination with gemcitabine and cisplatin.	Drug: QL1706; 5 mg/kg, intravenous infusion,D1; Drug: Gemcitabine; 1000 mg/m2 administered as IV infusion on D1/D8 of each cycle.; Drug: Cisplatin; 25 mg/m2, intravenous infusion, D1/D8, up to 8 cycles.
Experimental: QLS31905 + gemcitabine+cisplatin+ QL1706; Biliary tract cancer will be treated with QLS31905 at doses determined by the phase I study in combination with gemcitabine and cisplatin+ QL1706.	Drug: QLS31905; Administered as an intravenous infusion.; Drug: QL1706; 5 mg/kg, intravenous infusion,D1; Drug: Gemcitabine; 1000 mg/m2 administered as IV infusion on D1/D8 of each cycle.; Drug: Cisplatin; 25 mg/m2, intravenous infusion, D1/D8, up to 8 cycles.
Experimental: QLS31905 + standard chemotherapy; Other solid tumor participants will be treated with QLS31905 at doses determined by the phase I study in combination with standard chemotherapy recommended by guidelines.	Drug: QLS31905; Administered as an intravenous infusion.; Drug: Chemotherapy drug; Standard chemotherapy recommended by guidelines.
Experimental: QL1706 + standard chemotherapy; Other solid tumor participants will be treated with QL1706 in combination with standard chemotherapy recommended by guidelines.	Drug: QL1706; 5 mg/kg, intravenous infusion,D1; Drug: Chemotherapy drug; Standard chemotherapy recommended by guidelines.
Experimental: QLS31905 + standard chemotherapy + QL1706; Other solid tumor participants will be treated with QLS31905 at doses determined by the phase I study in combination with standard chemotherapy and QL1706.	Drug: QLS31905; Administered as an intravenous infusion.; Drug: QL1706; 5 mg/kg, intravenous infusion,D1; Drug: Chemotherapy drug; Standard chemotherapy recommended by guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR)	Approximately 24 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 24 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 24 months
Number of participants with laboratory value abnormalities	Number of participants with potentially clinically significant laboratory values.	Approximately 24 months
Duration of Response (DOR)	DOR is defined as the time from the date of the first response (CR/PR) until the date of radiological progressive disease or death due to any cause (whichever occurs first).	Approximately 24 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 radiological progressive disease or death due to any cause (whichever occurs first).	Approximately 24 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 24 months
Maximum concentration (Cmax)	Cmax will be derived from the PK serum samples collected.	Approximately 24 months
Time of the maximum concentration (Tmax)	Tmax will be derived from the PK serum samples collected.	Approximately 24 months
Terminal elimination half-life (T1/2)	T1/2 will be derived from the PK serum samples collected.	Approximately 24 months
Clearance (CL)	CL will be derived from the PK serum samples collected.	Approximately 24 months
Apparent volume of distribution during the terminal phase (Vz)	Vz will be derived from the PK serum samples collected.	Approximately 24 months
Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	Approximately 24 months

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 1, 2024
• First Submitted That Met QC Criteria: June 1, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin; Gemcitabine
• Other Study ID Numbers: QLS31905-202

Drug and device information, study documents

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