A Phase Ib Study of Tislelizumab Plus SYS6010 in Immunotherapy-Pretreated Locally Advanced or Metastatic NSCLC

NCT07692048 | Not Yet Recruiting Phase 1

• 1 other identifier: SYS6010-2025-11-17-YSW
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Patients with driver gene-negative non-small cell lung cancer (NSCLC) who experience treatment failure following immune checkpoint inhibitor (ICI) therapy have limited subsequent treatment options, representing an unmet clinical need. EGFR is commonly expressed in EGFR wild-type NSCLC and represents a potential target for therapeutic intervention. Antibody-drug conjugates (ADCs) combine the high targeting specificity of antibodies with the potent cytotoxic effects of payloads. SYS6010 is an EGFR-targeting ADC conjugated to a topoisomerase I inhibitor. Preclinical and clinical studies suggest that the combination of ADCs and ICIs can synergistically enhance anti-tumor efficacy through multiple immunomodulatory mechanisms. Tislelizumab is an approved PD-1 inhibitor for advanced NSCLC. This study aims to evaluate the safety and efficacy of SYS6010 in combination with tislelizumab in patients with driver gene-negative NSCLC who have failed prior PD-1/PD-L1 inhibitor therapy. Methods: This is an exploratory clinical trial enrolling patients with driver gene-negative NSCLC who have failed prior PD-1 or PD-L1 inhibitor therapy. The primary objective is to evaluate the safety of the combination therapy, with primary endpoints including the incidence, severity, and type of adverse events (AEs) according to NCI-CTCAE v6.0 criteria. Secondary objectives include assessing efficacy (objective response rate \[ORR\], disease control rate \[DCR\], duration of response \[DOR\], progression-free survival \[PFS\], overall survival \[OS\]) and exploring the association of potential predictive or prognostic biomarkers (e.g., EGFR and PD-L1 expression levels) with response to study treatment.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• incidence of adverse effect

  From date of first administration up to approximately 3.5 years after the last patient is administrated

Secondary Outcomes (5)

• Objective Response Rate（ORR）

  Approximately 9-11 weeks after the first dose

• Disease Control Rate（DCR）

  From date of first administration up to approximately 3.5 years after the last patient is administrated

• Duration of Response(DOR)

  From date of first administration up to approximately 3.5 years after the last patient is administrated

• Progression-Free Survival(PFS)

  From date of first administration up to approximately 3.5 years after the last patient is administrated

• Overall Survival (OS)

  From date of first administration up to approximately 5.5 years after the last patient is administrated

Other Outcomes (2)

• EGFR protein expression

  From date of first administration up to approximately 5.5 years after the last patient is administrated

• PD-L1 protein expression

  From date of first administration up to approximately 5.5 years after the last patient is administrated

Study Arms (1)

Tislelizumab plus SYS6010 in Immunotherapy-Pretreated Locally Advanced or Metastatic NSCLC

EXPERIMENTAL

Drug: SYS6010

Interventions

SYS6010 DRUG

SYS6010 4.2mg/kg,Ivgtt，Q3W，plus Tislelizumab，200 mg，Ivgtt，Q3W

Tislelizumab plus SYS6010 in Immunotherapy-Pretreated Locally Advanced or Metastatic NSCLC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically or cytologically confirmed locally advanced or metastatic NSCLC that is not amenable to curative surgery or radiotherapy.
• Have no known EGFR mutations, ALK rearrangements, or ROS1 rearrangements.
• Have experienced radiographic disease progression per RECIST v1.1 after prior treatment with an anti-PD-(L)1 antibody for locally advanced or metastatic NSCLC, with prior therapy including:
• Progression on anti-PD-(L)1 antibody combined with platinum-based chemotherapy (second-line); or
• Progression on platinum-based chemotherapy following prior anti-PD-(L)1 monotherapy (third-line); or
• Progression on anti-PD-(L)1 monotherapy and considered unfit for platinum-based chemotherapy (second-line); or
• Progression on anti-PD-(L)1-containing therapy following prior platinum-based chemotherapy (third-line).
• a. Adjuvant or neoadjuvant therapy is counted as one prior line of therapy if the time between the last dose of chemotherapy and tumour recurrence is ≤ 6 months.
• Have at least one evaluable tumour lesion per RECIST v1.1 (see Appendix 1).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 2).
• Have a life expectancy of ≥ 3 months as assessed by the investigator.
• Agree to undergo tumour tissue biopsy before the first study treatment and during the treatment period, whenever clinically feasible.
• Have adequate bone marrow, hepatic, renal, and coagulation function confirmed by laboratory tests obtained within 7 days before the first dose (transfusion or growth factor support is not permitted within 2 weeks prior to the screening assessment):
• Bone marrow function: Absolute neutrophil count ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L; haemoglobin ≥ 90 g/L.
• Hepatic function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (or ≤ 3 × ULN in the presence of liver metastases); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5.0 × ULN in the presence of liver metastases); albumin ≥ 28 g/L.

You may not qualify if:

• Have histologically or cytologically confirmed locally advanced or metastatic NSCLC that is not amenable to curative surgery or radiotherapy.
• Have no known EGFR mutations, ALK rearrangements, or ROS1 rearrangements.
• Have experienced radiographic disease progression per RECIST v1.1 after prior treatment with an anti-PD-(L)1 antibody for locally advanced or metastatic NSCLC, with prior therapy including:
• Progression on anti-PD-(L)1 antibody combined with platinum-based chemotherapy (second-line); or
• Progression on platinum-based chemotherapy following prior anti-PD-(L)1 monotherapy (third-line); or
• Progression on anti-PD-(L)1 monotherapy and considered unfit for platinum-based chemotherapy (second-line); or
• Progression on anti-PD-(L)1-containing therapy following prior platinum-based chemotherapy (third-line).
• a. Adjuvant or neoadjuvant therapy is counted as one prior line of therapy if the time between the last dose of chemotherapy and tumour recurrence is ≤ 6 months.
• Have at least one evaluable tumour lesion per RECIST v1.1 (see Appendix 1).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 2).
• Have a life expectancy of ≥ 3 months as assessed by the investigator.
• Agree to undergo tumour tissue biopsy before the first study treatment and during the treatment period, whenever clinically feasible.
• Have adequate bone marrow, hepatic, renal, and coagulation function confirmed by laboratory tests obtained within 7 days before the first dose (transfusion or growth factor support is not permitted within 2 weeks prior to the screening assessment):
• Bone marrow function: Absolute neutrophil count ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L; haemoglobin ≥ 90 g/L.
• Hepatic function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (or ≤ 3 × ULN in the presence of liver metastases); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5.0 × ULN in the presence of liver metastases); albumin ≥ 28 g/L.

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Please Select, 610041, China

Location

Central Study Contacts

Benxia Zhang, PhD

CONTACT

86（028）85421606; zhangbenxia1007@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 9, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)