Phase III Clinical Study of HB0025 Combined With Chemotherapy Versus Tislelizumab Combined With Chemotherapy as First-Line Treatment for Advanced Nonsquamous Non-Small Cell Lung Cancer

NCT07383116 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: HB0025-C-0303
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, controlled, double-blind, multicenter Phase III registration clinical trial, aiming to evaluate the efficacy and safety of HB0025 combined with chemotherapy (pemetrexed plus carboplatin/cisplatin) versus tislelizumab combined with chemotherapy (pemetrexed plus carboplatin/cisplatin) as a first-line treatment for unresectable locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) nonsquamous non-small cell lung cancer (NSCLC). The study will take progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) as the primary endpoint, and plans to enroll approximately 500 subjects. After being eligible for screening, patients will be randomly assigned to the study groups at a ratio of 1:1 to receive either HB0025 combined with chemotherapy (experimental group) or tislelizumab combined with chemotherapy (control group). Both regimens will be administered once every 3 weeks (Q3W). After completing 4 cycles of treatment, patients will enter the maintenance therapy phase with HB0025 or tislelizumab plus pemetrexed (Q3W). The treatment will last until the investigator determines that there is no longer clinical benefit (based on comprehensive assessment of RECIST v1.1 imaging results and clinical symptoms), intolerable toxicity occurs, 35 cycles of study treatment are completed, or other treatment termination criteria specified in the protocol are met, whichever comes first.

Conditions

Non Squamous Non-small Cell Lung Cancer

Keywords

HB0025; Fist Line treatment; nonsq NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first)

  Up to approximately 24 Months

Secondary Outcomes (12)

• Overall Survival (OS)

  Up to 24 Months

• Objective Response Rate (ORR)

  Up to 24 Months

• Disease control rate (DCR)

  Up to 24 Months

• Duration of response (DOR)

  Up to 24 Months

• Time to Progression(TTP)

  Up to 24 Months

Other Outcomes (1)

• PD-L1 expression

  Approximately 16 months.

Study Arms (2)

HB0025

EXPERIMENTAL

HB0025 combined with Pemetrexed for Injection plus Carboplatin for Injection or Cisplatin for Injection, intravenous infusion, once every 3 weeks (Q3W)

Drug: Pemetrexed injection; Drug: Carboplatin Injection; Drug: Cisplatin injection; Drug: HB0025 Injection

Tislelizumab

ACTIVE COMPARATOR

Tislelizumab combined with Pemetrexed for Injection plus Carboplatin for Injection or Cisplatin for Injection, intravenous infusion, once every 3 weeks (Q3W)

Drug: Pemetrexed injection; Drug: Carboplatin Injection; Drug: Cisplatin injection; Drug: Tislelizumab

Interventions

Pemetrexed injection DRUG

500 mg/m², Q3W.

HB0025; Tislelizumab

Carboplatin Injection DRUG

AUC 5, Q3W.

HB0025; Tislelizumab

Cisplatin injection DRUG

75 mg/m², Q3W.

HB0025; Tislelizumab

HB0025 Injection DRUG

HB0025 Injection, ivgtt, Q3W，developed by Sponsor Huaota.

HB0025

Tislelizumab DRUG

Tislelizumab, Active Control, intravenous infusion, once every 3 weeks (Q3W)

Tislelizumab

Eligibility Criteria

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

You may qualify if:

• Able to fully understand and voluntarily sign the informed consent form, and willing and able to comply with the clinical study procedures and follow-up visits.
• Aged 18 to 75 years old (inclusive of both upper and lower limits), male and female subjects are eligible.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1.
• Expected survival ≥ 12 weeks.
• Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous non-small cell lung cancer (NSCLC) (confirmed per the 9th Edition of the TNM Staging System for Lung Cancer by the Union for International Cancer Control \[UICC\] and the American Joint Committee on Cancer \[AJCC\]), which is inoperable for radical resection and ineligible for radical concurrent/sequential chemoradiotherapy as well as immunotherapy as consolidation treatment.
• Note: For subjects with locally advanced (Stage IIIB/IIIC) non-squamous NSCLC who are inoperable for radical resection and ineligible for radical concurrent/sequential chemoradiotherapy as well as immunotherapy as consolidation treatment, assessment by relevant specialist physicians and provision of written documentation are required for confirmation.
• No prior systemic antineoplastic treatment for the study disease (including systemic chemotherapy, targeted therapy, and immunotherapy).
• Note: Subjects who previously received neoadjuvant, adjuvant, or radical concurrent/sequential chemoradiotherapy for non-metastatic disease with curative intent are eligible if disease progression occurs \> 180 days after the last dose of prior treatment.
• Subjects must provide tumor tissue samples (archived or freshly obtained) collected at or after the diagnosis of locally advanced or metastatic tumor for central laboratory testing of PD-L1 expression.
• Note: The following samples are not accepted: fine-needle aspiration samples (without intact tissue structure, only cell suspensions or smears), brush cytology samples, cell smears from centrifuged pleural effusion drainage, bronchoalveolar lavage fluid samples, and bone lesions without soft tissue components or decalcified bone tumor samples. Tumor lesions used for fresh tissue biopsy should not be designated as RECIST v1.1 target lesions, unless the lesion is the only measurable lesion. For archived samples, they must be collected after the last systemic treatment, and the collection site must not have received radiotherapy. If a subject's archived samples do not meet the above requirements and the investigator judges that a biopsy is not in the subject's best interest, the use of archived samples may be permitted after discussion with the sponsor.
• No sensitive EGFR mutations or ALK gene rearrangements. Prior tissue-based test reports for EGFR and ALK status must be provided. If the test reports do not meet the study requirements or are unavailable, tumor tissue samples must be provided for assessment of EGFR and ALK status (tested by a local laboratory recognized by the study site or the central laboratory) before enrollment.
• Note: For subjects with squamous NSCLC (excluding mixed-type NSCLC, e.g., adenosquamous carcinoma) who have a smoking history or are current smokers, if the prior EGFR and ALK status is unknown, testing for these markers is not required before enrollment, and they will be deemed negative.
• Per RECIST v1.1 criteria (see Appendix 2), the subject must have at least one measurable (non-brain metastatic) lesion suitable for repeated and accurate measurement. Tumor lesions previously treated with radiotherapy or other local therapies must not be designated as target lesions, unless:
• The lesion is the only measurable lesion, and the investigator can provide imaging evidence (both pre- and post-local treatment) confirming clear disease progression of the lesion following local therapy; The lesion used for fresh tissue biopsy must not be designated as a target lesion, unless it is the only measurable lesion and the biopsy date is more than 4 weeks prior to the first dose of study treatment.
• Confirmed adequate organ function, with mandatory compliance with the following laboratory parameters:

You may not qualify if:

• Histologically confirmed presence of any small cell carcinoma, neuroendocrine carcinoma, or sarcoma components \[mixed-type NSCLC (e.g., adenosquamous carcinoma) is permitted for enrollment\].
• Known presence of driver gene alterations with approved first-line therapeutic options, such as sensitive EGFR mutations, ALK fusion, ROS1 fusion, BRAF V600 mutation, NTRK fusion, MET exon 14 skipping mutation, or RET fusion.
• History of a second primary malignancy within 5 years before screening (enrollment is permitted for other malignancies cured by local treatment, e.g., carcinoma in situ of the cervix, localized cutaneous squamous cell carcinoma, basal cell carcinoma, ductal carcinoma in situ of the breast, \< T1 urothelial carcinoma, and papillary microcarcinoma of the thyroid).
• Symptomatic central nervous system (CNS) metastasis. For subjects with asymptomatic CNS metastasis or those with symptomatically stable CNS metastasis for ≥ 4 weeks prior to randomization, enrollment is permitted only if all the following criteria are met:
• No metastasis to the meninges, midbrain, pons, medulla oblongata, spinal cord, or spinal cord compression; ② No increase in lesion size or new lesions after treatment;
• No history of intracranial hemorrhage;
• Discontinuation of corticosteroid therapy for ≥ 2 weeks prior to randomization; ⑤ No significant perilesional edema surrounding brain metastases; ⑥ The longest diameter of brain metastases ≤ 1.5 cm.
• Prior receipt of immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1/L1/L2, anti-CTLA-4 agents), immune checkpoint agonists (e.g., ICOS, CD40, GITR, OX40, CD137 agents), or cellular immunotherapy, or any treatment targeting the tumor immune mechanism. Additionally, for subjects who previously received PD-(L)1 inhibitors in the neoadjuvant/adjuvant setting or as consolidation therapy after definitive chemoradiotherapy, enrollment may be permitted (with sponsor approval) if the interval between the end of the last treatment and the occurrence of disease progression is more than 12 months.
• Note: For subjects with prior PD-(L)1 inhibitor exposure:
• Enrollment is prohibited if the subject experienced ≥ Grade 3 immune-related adverse events (irAEs) caused by prior immunotherapy (excluding endocrine-related irAEs), irAEs leading to permanent treatment discontinuation, ≥ Grade 2 immune-related cardiotoxicity, or immune-related neurological or ophthalmic irAEs of any grade; Screening is prohibited if all adverse events caused by prior immunotherapy have not been fully resolved or resolved to Grade 1 before study screening. For subjects with ≥ Grade 2 endocrine-related irAEs, enrollment is permitted if the condition is stable and asymptomatic with appropriate replacement therapy.
• Prior receipt of systemic anti-angiogenic therapy, including but not limited to bevacizumab and its biosimilars, Endostar, small-molecule TKIs, and ramucirumab.
• Prior anti-tumor therapy or concomitant medication (the washout period is calculated from the end date of the last treatment):a) Participation in any clinical trial within 28 days prior to the first dose;b) Receipt of anti-tumor therapy within 4 weeks prior to the first dose or within 5 half-lives of the drug (whichever is longer), including but not limited to chemotherapy, radiotherapy (thoracic radiotherapy with a dose \> 30 Gy within 180 days prior to the first dose; non-thoracic radiotherapy with a dose \> 30 Gy within 4 weeks prior to the first dose; local palliative radiotherapy with a dose ≤ 30 Gy for non-target lesions within 2 weeks prior to the first dose), targeted therapy, immunotherapy, or endocrine therapy;c) Use of Chinese herbal medicines (including patent Chinese medicines) with anti-tumor indications within 2 weeks prior to the first dose; use of non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 for the treatment of thrombocytopenia) within 2 weeks prior to the first dose;d) Need for systemic administration of corticosteroids at a dose \> 10 mg/day of prednisone or equivalent dose, or other immunomodulators within 2 weeks prior to randomization. \[Short-term administration (≤ 7 days) for prophylaxis (e.g., contrast agent allergy) or treatment of non-autoimmune diseases (e.g., delayed hypersensitivity reaction caused by allergen exposure), or local administration (e.g., intraocular, intra-articular, intranasal, or inhaled administration) is permitted for enrollment\];e) Use or current use of anticoagulants such as warfarin, heparin (excluding heparin for catheter locking or deep vein catheterization), dabigatran etexilate, rivaroxaban, etc., or antiplatelet drugs such as aspirin, clopidogrel, dipyridamole, cilostazol, or other known antiplatelet agents within 2 weeks prior to the first dose.
• Major surgery or severe trauma within 4 weeks before the first dose of study treatment; inadequate recovery from prior surgery (as judged by the investigator); anticipated need for major surgery during the study; minor local surgery (e.g., needle biopsy, endoscopy, interventional procedure/examination, excluding vascular access establishment) within 7 days before randomization; presence of incompletely healed surgical incisions or wounds.
• Active autoimmune disease requiring systemic treatment (e.g., treatment with immunomodulators or corticosteroids) within 2 years before screening, except for replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency).
• Presence of any of the following infections:

Sponsors & Collaborators

• Shanghai Huaota Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

The East Hospital Affiliated to Tongji University

Shanghai, Shanghai 200120, China

Location

MeSH Terms

Interventions

Pemetrexed; Carboplatin; Cisplatin; tislelizumab

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Caicun Zhou, MD

  The East Hospital Affiliated to Tongji University, Shanghai, Shanghai 200120

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caicun Zhou, MD

CONTACT

86 021-58822171; CAICUNZHOUDR@TONGJI.EDU.CN

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study plans to enroll approximately 500 subjects, who will be randomly assigned at a 1:1 ratio to either the HB0025 plus chemotherapy group (experimental group, \~250 subjects) or the tislelizumab plus chemotherapy group (control group, \~250 subjects). Subjects in the experimental group will receive HB0025 combined with chemotherapy, while those in the control group will receive tislelizumab combined with chemotherapy, with both regimens administered once every 3 weeks (Q3W). After completing 4 cycles of treatment, all subjects will proceed to the maintenance therapy phase with either HB0025 or tislelizumab plus pemetrexed (Q3W). Experimental group: HB0025 combined with pemetrexed plus carboplatin/cisplatin Control group: Tislelizumab combined with pemetrexed plus carboplatin/cisplatin

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: February 3, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): April 10, 2028
• Study Completion (Estimated): April 10, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

CN (1)