Combination of QLS31905, QL2107 and Chemotherapy as First-line Therapy in CLDN18.2-positive Unresectable Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

An Open-label, Multicenter Phase II Clinical Study of QLS31905 for Injection Combined With QL2107 Injection and XELOX Regimen in the First-line Treatment of CLDN18.2-positive Unresectable Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

This is an open-label, multicenter Phase II clinical study aimed at evaluating the tolerability, safety, efficacy, PK profile, and immunogenicity of QLS31905 for Injection combined with QL2107 Injection and XELOX regimen in the first-line treatment of CLDN18.2-positive unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: QLS31905 for Injection; Drug: QL2107 Injection; Drug: Oxaliplatin Injection; Drug: Capecitabine Tablets

Detailed Description

QLS31905 is a bispecific antibody targeting CD3 and CLDN18.2 independently developed by Qilu Pharmaceutical Co., Ltd.

QL2107 is a biosimilar of pembrolizumab (Keytruda®) developed by Qilu Pharmaceutical Co., Ltd.

This is an open-label, multicenter Phase II clinical study aimed at evaluating the tolerability, safety, efficacy, PK profile, and immunogenicity of QLS31905 for Injection combined with QL2107 Injection and XELOX regimen in the first-line treatment of CLDN18.2-positive unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lin Shen, PHD; 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 with unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma confirmed by histopathological or cytological examination;
• Subjects with at least one measurable lesion designated as a target lesion, as assessed by the investigator according to RECIST v1.1. Lesions that have received radiotherapy or other local treatments may be considered measurable if they demonstrate imaging PD;
• No prior systemic anti-tumor treatment for locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Exclusion Criteria:

• Subjects with a known history of severe or repeated allergy, intolerance, or contraindication to QLS31905, QL2107, or other large molecule protein preparations, as well as Oxaliplatin Injection or Capecitabine Tablets and any components in their preparations;
• Subjects had other second primary malignancies within 5 years prior to the first dose;
• Subjects with clinically significant hemorrhage within 3 months before the first dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QLS31905+QL2107+ XELOX; QLS31905+QL2107+ oxaliplatin + capecitabine	Drug: QLS31905 for Injection; QLS31905 for Injection; Drug: QL2107 Injection; QL2107 Injection; Drug: Oxaliplatin Injection; Oxaliplatin Injection; Drug: Capecitabine Tablets; Capecitabine Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	Dose Limiting Toxicity，for Dose Escalation Stage	up to 42 days following first dose
MTD	Maximum Tolerated Dose，for Dose Escalation Stage.	up to 42 days following first dose
ORR (Objective Response Rate)	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 per RECIST 1.1	Approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax)	Cmax 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
Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	Approximately 24 months
AE (adverse events)	AEs are any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Approximately 24 months
DOR (Duration of Response)	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
PFS (Progression Free Survival)	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
OS (Overall Survival)	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

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: CLDN18.2, gastric or gastroesophageal junction (GEJ) adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Capecitabine; Oxaliplatin
• Other Study ID Numbers: QLS31905-203

Drug and device information, study documents

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