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

Phase 2

Not yet recruiting

• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Interventions: Drug: QLS31905 for Injection; Drug: QL2107 Injection; Drug: Oxaliplatin Injection; Drug: Capecitabine Tablets

• Registration Number: NCT06942767
• Lead Sponsor: Qilu Pharmaceutical Co., Ltd.

Brief Summary

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.

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 Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-17
• Study First Submitted QC: 2025-04-17
• Last Update Submitted: 2025-04-23
• Study First Posted: 2025-04-24
• Last Update Posted: 2025-04-27
• Study Start: 2025-06
• Primary Completion: 2026-12
• Study Completion: 2028-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
QLS31905+QL2107+ XELOX	QLS31905 for Injection	QLS31905+QL2107+ oxaliplatin + capecitabine
QLS31905+QL2107+ XELOX	QL2107 Injection	QLS31905+QL2107+ oxaliplatin + capecitabine
QLS31905+QL2107+ XELOX	Oxaliplatin Injection	QLS31905+QL2107+ oxaliplatin + capecitabine
QLS31905+QL2107+ XELOX	Capecitabine Tablets	QLS31905+QL2107+ oxaliplatin + capecitabine

Primary Outcome Measures

Name	Time	Method
DLT	up to 42 days following first dose	Dose Limiting Toxicity，for Dose Escalation Stage
MTD	up to 42 days following first dose	Maximum Tolerated Dose，for Dose Escalation Stage.
ORR (Objective Response Rate)	Approximately 24 months	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

Secondary Outcome Measures

Name	Time	Method
Number of anti-drug antibody (ADA) Positive Participants	Approximately 24 months	Immunogenicity will be measured by the number of participants that are ADA positive.
DOR (Duration of Response)	Approximately 24 months	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)
AE (adverse events)	Approximately 24 months	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.
PFS (Progression Free Survival)	Approximately 24 months	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).
OS (Overall Survival)	Approximately 24 months	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.
Maximum concentration (Cmax)	Approximately 24 months	Cmax will be derived from the PK serum samples collected.
Terminal elimination half-life (T1/2)	Approximately 24 months	T1/2 will be derived from the PK serum samples collected.