Efficacy and Safety of QL1706 Plus Lenvatinib As 2nd Line Theapy in Patients with Metastatic Esophageal Carcinoma After Disease Progression on ICIs Therapy

Phase 1

Not yet recruiting

• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Interventions: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4); Drug: Lenvatinib

• Registration Number: NCT06746961
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

Brief Summary

The purpose of this study is to assess the efficacy and safety of QL1706 plus lenvatinib in second-line therapy for patients with metastatic esophageal squamous cell carcinoma after progression on immune checkpoint inhibitor therapy

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-12-19
• Study First Submitted QC: 2024-12-19
• Last Update Submitted: 2024-12-19
• Study First Posted: 2024-12-24
• Last Update Posted: 2024-12-24
• Study Start: 2025-01
• Primary Completion: 2026-07
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

1. Subjects participate voluntarily and sign informed consent.
2. 18-75 years, male or female.
3. Histologically or cytologically verified diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma
4. Patients who have disease progression verified by imaging on standard first-line immunotherapy with anti-PD-1/PD-L1 antibodies
5. At least 1 measurable target lesion according to Response Evaluation in Solid Tumors (RECIST 1.1).
6. ECOG PS 0-1

Exclusion Criteria

1. Presence of any active autoimmune disease or history of autoimmune disease (such as: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism)
2. Those who are taking immunosuppressants or systemic hormonal therapy for immunosuppressive purposes (dose> 10 mg/day prednisone or other equivalent cortiremonial hormones) and are taking within 2 weeks before recruitment
3. Severe allergic reaction to other monoclonal antibodies
4. Those who terminated treatment due to related toxicity during anti-PD-1/PD-L1 antibody treatment
5. Prior treatment with bispecific anti-PD-1/CTLA-4 checkpoint blockades or VEGFR inhibitors

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
QL1706 plus Lenvatinib	QL1706 (bispecific antibody targeting PD-1 and CLTA-4)	QL1706 will be administrated at a dose of 5 mg/kg intravenously (IV), every 3 weeks, until progressive disease or intolerable or other reasons according to the criteria for termination of treatment. QL1706 will be administrated up to 2 year. Lenvatinib will be administrated at a dose of 8 mg or 12mg orally (PO) once daily (QD)
QL1706 plus Lenvatinib	Lenvatinib	QL1706 will be administrated at a dose of 5 mg/kg intravenously (IV), every 3 weeks, until progressive disease or intolerable or other reasons according to the criteria for termination of treatment. QL1706 will be administrated up to 2 year. Lenvatinib will be administrated at a dose of 8 mg or 12mg orally (PO) once daily (QD)

Primary Outcome Measures

Name	Time	Method
Phase II: Overall Survival (OS) in all participants	up to ~48 months	OS is defined as the time from the first administration to death due to any cause.
Phase Ib：Dose Limiting Toxicities (DLTs) and recommended phase 2 dose (PR2D)	up to ~21 days	Hematologic DLTs are defined as: 1. Grade 4 neutropenia lasting for ≥7 days; 2. febrile neutropenia not associated with the underlying disease,; 3. Grade 3 thrombocytopenia with bleeding, Grade ≥3 thrombocytopenia requiring platelet transfusion, Grade 4 thrombocytopenia, .

Secondary Outcome Measures

Name	Time	Method
PFS	up to ~42 months	PFS is defined as the time from the first administration to the first documented progressive disease (PD) per RECIST 1.1 by investigators or death due to any cause, whichever occurs first.
ORR	up to ~42 months	ORR is defined as the percentage of participants with Complete Response or Partial Response per RECIST 1.1 assessed by the investigators.
DOR	up to ~42 months	For participants who demonstrate a confirmed CR or PR, per RECIST 1.1 by the investigators, DOR is defined as the time from first documented evidence of CR or PR until PD or death.
Number of Participants With AEs	Up to ~53 months	An AE is 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.