A Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer
A Phase II/III, Randomized, Multicenter, Open-Label Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer
1 other identifier
interventional
450
1 country
64
Brief Summary
This is a Phase II/III, randomized, open-label, active-controlled, multicenter study to compare intravenous uliledlimab combined with toripalimab, toripalimab monotherapy, and pembrolizumab monotherapy in patients with previously untreated locally advanced unresectable or metastatic PD-L1-positive (tumor proportion score \[TPS\] ≥ 1%) and CD73-positive (TC/IC \> 30%; TC/IC defined as the higher of either the proportion of CD73-positive tumor cells or the proportion of CD73-positive immune cells at any intensity \[IHC1+ or above\]) NSCLC who are not suitable for targeted therapies such as EGFR, ALK, etc. The number of enrolled subjects with PD-L1 TPS ≥ 50% will be limited to approximately 60% of the total sample size to reflect the natural prevalence of advanced NSCLC. Patients who have received adjuvant or neoadjuvant therapy other than immune checkpoint inhibitor treatments are allowed to participate in this study, provided that such treatments have been completed at least 12 months prior to the occurrence of recurrence or metastasis. During the screening period, tumor samples will be collected in advance and tested by the central laboratory for PD-L1 expression levels using the PD-L1 IHC 22C3 pharmDx assay and CD73 expression levels using the CD73 antibody assay (immunohistochemistry). Previous PD-L1 testing results obtained using the PD-L1 IHC 22C3 pharmDx assay will be accepted. Patients with PD-L1 positive expression (TPS ≥ 1%) and high CD73 expression (TC/IC \> 30%) will meet the inclusion criteria. Patients who do not meet the eligibility criteria as judged by the investigator may be re-screened once. Patients with non-squamous NSCLC will be required to confirm the absence of EGFR-sensitive mutations or ALK fusion; patients with unknown EGFR and ALK expression status will be required to undergo testing and provide clinical laboratory test results prior to study enrollment, and may be enrolled after relevant driver gene mutations are ruled out. Meanwhile, patients with other definite actionable driver gene alterations (such as: ROS1 fusions, RET fusions, NTRK1/2/3 fusions, BRAF V600E mutations, MET14 exon skipping mutations, etc.) will be excluded from this study. Controversial cases with actionable gene mutations will be submitted to the study expert panel for joint decision. This study includes Phase II and Phase III stages. Approximately 150 subjects will be enrolled in the Phase II stage. Based on the evaluation of the efficacy, safety, PK, and PD results of the Phase II study, a decision will be made on whether to proceed to the Phase III study. Approximately 300 subjects will be enrolled in the Phase III stage.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2024
Typical duration for phase_2
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 28, 2024
CompletedFirst Submitted
Initial submission to the registry
April 22, 2025
CompletedFirst Posted
Study publicly available on registry
May 22, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 5, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2028
January 30, 2026
January 1, 2026
4.4 years
April 22, 2025
January 28, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
From the date of randomization to the date of first documented disease progression (assessed by a blinded independent central review [BICR] according to RECIST v1.1) or death from any cause, whichever occurs first,assessed up to 6 months
Study Arms (3)
Group A
EXPERIMENTALGroup B
ACTIVE COMPARATORGroup C
SHAM COMPARATORInterventions
30 mg/kg, administered on Days 1 and 8 of Cycle 1 (C1D1 and C1D8), then once every 3 weeks (Q3W) starting from C2D1,
Eligibility Criteria
You may qualify if:
- Patients aged ≥ 18 years at the time of signing the ICF
- Patients with histologically or cytologically confirmed stage IIIB, IIIC, or IV NSCLC (according to the American Joint Committee on Cancer Staging System, 8th edition) who are not suitable for radical surgery and/or radiotherapy (with or without chemotherapy).
- Patients who have not received prior systemic therapy for their locally advanced or metastatic diseases.
- Patients with measurable lesions as assessed by the investigator at the study site based on RECIST v1.1. Target lesions located in a previously irradiated region will be considered measurable only if there is documented evidence of disease progression
- Patients with non-squamous NSCLC who are confirmed to have no EGFR-sensitive mutations or ALK fusions.
- Patients with PD-L1 TPS ≥ 1% and CD73 TC/IC \> 30% (IHC1+ or higher). It will be tested by the central laboratory for PD-L1 expression levels using the PD-L1 IHC 22C3 pharmDx assay, and CD73 expression levels using the CD73 antibody assay.
- Patients with a life expectancy of at least 3 months.
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Patients with adequate organ function
- Patients with negative HIV testing at screening.
- Patients with negative hepatitis B virus surface antigen (HBsAg) or inactive hepatitis B (HBsAg positive with HBV-DNA copy number ≤ ULN, ALT ≤ ULN, and no treatment is required in the investigator's opinion) at screening.
- Patients with negative hepatitis C virus (HCV) antibody at screening, or positive HCV antibody and negative HCV RNA at screening.
- For women of childbearing potential: A urine or serum pregnancy test must be negative within 72 hours prior to the first dose of study drug. If the urine pregnancy test result is positive or cannot be confirmed as negative, a serum pregnancy test should be performed.
- For male subjects with female partners of childbearing potential: They must agree to use an effective method of contraception from the first dose of study drug to 180 days after the last dose of study drug.Male subjects with pregnant partners will be required to agree to use condoms; pregnant partners will not be required to use additional methods of contraception.
- Patients who voluntarily agree to participate in the study and sign a written ICF
You may not qualify if:
- Patients who are currently pregnant, breastfeeding, or planning to conceive or give birth within the expected duration of this study.
- Patients previously treated with immune checkpoint inhibitors.
- Patients who are receiving or have completed systemic immune agonist therapy (including but not limited to: interferon and interleukin-2) within 4 weeks prior to the first dose or 5 drug elimination half-lives (whichever is longer).
- Patients who have received oral or intravenous antibiotic therapy within 2 weeks prior to starting study treatment, except for prophylactic use.
- Patients who have undergone major surgery within 4 weeks prior to starting study treatment, except for diagnostic surgery.
- Patients who have received a live attenuated vaccine within 30 days prior to starting study treatment. Seasonal influenza vaccines that do not contain live viruses are permitted.
- Patients who are currently participating in another clinical trial and receiving study treatment, or who have participated in a clinical trial and received investigational drug or device treatment within 4 weeks prior to enrollment.
- Patients who have received any anti-tumor therapeutic agents containing traditional Chinese medicine ingredients within 4 weeks prior to starting study treatment.
- Patients who have previously received an allogeneic tissue/organ transplant.
- Patients who are expected to require any other form of anti-tumor therapy during the course of the study.
- Patients with angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, unstable arrhythmia, pulmonary embolism, or treatment with percutaneous transluminal coronary angioplasty or coronary artery bypass grafting within 6 months prior to study treatment.
- Patients with hypertension (defined as systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg) or CTCAE Grade ≥2 hypotension.
- Patients with uncontrolled or symptomatic hypercalcaemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN).
- Patients with known previous malignancies other than NSCLC, except for those who have received radical therapy, have no evidence of disease recurrence within 5 years, and are assessed by the investigator to be at low risk of recurrence.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (64)
Anyang Tumour Hospital
Anyang, China
Beijing Chest Hospital, Capital Medical University
Beijing, China
Bejing Chao-Yang Hospital, Capital Medical University
Beijing, China
The First Affiliated Hospital of Bengbu Medical University
Bengbu, China
Binzhou Medical University Hospital
Binzhou, China
The Third Xiangya Hospital of Central South University
Changsha, China
Xiangya Hospital of Central South University
Changsha, China
Army characteristic Hospital Center( Daping Hospital of the Third Military Medical University)
Chongqing, China
Chongqing University Cancer Hospital
Chongqing, China
Chongqing University Three Gorges Hospital
Chongqing, China
The People's Hospital of Dongguan
Dongguan, China
The first people's hospital of Foshan
Foshan, China
First Affiliated Hospital of Gannan Meidcal University
Ganzhou, China
Ganzhou People's Hospital
Ganzhou, China
Guangdong Provincial People's Hospital
Guangzhou, China
Guizhou Provincial People's Hospital
Guiyang, China
The Second Affiliated Hospital of Hainan Medical University
Haikou, China
Harbin Medical university cancer hospital
Ha’erbin, China
Anhui provincial cancer hospital
Hefei, China
The First Affiliated Hospital of Anhui Medical University
Hefei, China
Jiamusi Tumour Hospital
Jiamusi, China
Jiangmen Central hospital
Jiangmen, China
Jinan Central Hospital
Jinan, China
Affiliated Hospital of Jining Medical University
Jining, China
Linyi People's Hospital
Linyi, China
Lishui Central Hospital
Lishui, China
Liuzhou Central Hospital
Liuchow, China
Longyan First Hospital
Longyan, China
Jiangxi Cancer Hospital
Nanchang, China
The First Affiliated Hospital Of Nanchang University
Nanchang, China
Nanchong Central Hospital
Nanchong, China
Jiangsu Province Hospital
Nanjing, China
Guangxi Medical University Cancer Hospital
Nanning, China
The First Affiliated Hospital of Guangxi Medical University
Nanning, China
Nantong Tumor Hospital
Nantong, China
Nanyang Cenreal Hospital
Nanyang, China
The Second People's Hospital of Neijiang
Neijiang, China
Qingdao Central Hospital
Qingdao, China
The First People's Hospital Of Qujing
Qujing, China
Yuebei People's Hospital
Shaoguan, China
China Shenyang the Tenth People's Hospital(China Shenyang Chest Hospital)
Shenyang, China
The Fourth Hospital Of Hebei Medical University
Shijia Zhuang, China
Suining Central Hospital
Suining, China
First Hospital of Shanxi Medical University
Taiyuan, China
Taizhou Hospital of Zhejiang Province
Taizhou, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
The Second Affiliated Hospital Of Xi'an Jiaotong University
Xi'an, China
Xi'an Chest Hospital
Xi'an, China
Fujian Provincial Cancer Hospital
Xiamen, China
The First Affiliated Hospital Of Xiamen University
Xiamen, China
The Second Affiliated Hospital of Xiamen Medical College
Xiamen, China
Xiangyang Central Hospital
Xiangyang, China
Northern Jiangsu People's Hospital
Yangzhou, China
The Second People's Hospital Of Yibin
Yibin, China
Yichang Central People's Hospital
Yichang, China
Shanxi Yuncheng Central hospital
Yuncheng, China
The First Affiliated Hospital Of Henan University Of Science & Technology
Zhengzhou, China
The First Affiliated Hospital Of Zhengzhou University
Zhengzhou, China
Zhoukou Central hospital
Zhoukou, China
Zhujiang hospital of Southern Medical University
Zhujiang, China
Zibo Municipal Hospital
Zibo, China
The first people's hospital of Zunyi
Zunyi, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 22, 2025
First Posted
May 22, 2025
Study Start
March 28, 2024
Primary Completion (Estimated)
August 5, 2028
Study Completion (Estimated)
September 30, 2028
Last Updated
January 30, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share