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Not yet recruitingNCT07865910Updated Oct 8, 2026

A Study to Learn the Safety and Efficacy of HLX37 in Combination With Chemotherapy for First-line Treatment in Adult Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Phase 2/3 interventional study of Investigational drug: HLX37 dose1, IV, Q3W and PEMBROLIZUMAB (alone or when added to a regimen above) in NSCLC (Advanced Non-small Cell Lung Cancer), sponsored by Shanghai Henlius Biotech. Not yet recruiting at 16 sites in China. Open to participants aged 18 Days to 75 Days. Per ClinicalTrials.gov, last updated 2026-10-08.

Sponsored by Shanghai Henlius Biotech · Phase 2/3, Interventional, and Treatment

Updated Oct 8, 2026Newly registeredGo to Updates ↓
Phase
Phase 2/3
Study type
Interventional
Enrollment
1,438
Allocation
Randomized
Ages
18 Days to 75 Days
Sex
All
01

Study summary

This is a Randomized, Double-Blind, Multicenter, Phase II/III Study to Evaluate HLX37 (Recombinant Human Anti-PD-L1 and Anti-VEGF Bispecific Antibody) in Combination with Chemotherapy Versus Pembrolizumab in Combination with Chemotherapy for First-Line Therapy of Advanced Non-Small Cell Lung Cancer.The first phase of this study is a Phase II trial, with Substudy A enrolling approximately 90 participants and Substudy B enrolling approximately 90 participants. Based on your disease pathology type, the investigator will determine which substudy you are enrolled in. Eligible participants will be randomly assigned to one of three treatment groups in a 1:1:1 ratio (similar to flipping a coin or drawing names from a hat), giving each participant an equal 1/3 chance of being assigned to any given group. Within each substudy, approximately one-third of participants will receive HLX37 at dose1combined with chemotherapy, one-third will receive HLX37 at dose2 combined with chemotherapy, and one-third will receive pembrolizumab at 200 mg combined with chemotherapy. All three treatment groups will have a treatment schedule of every three weeks (Q3W).

The second phase of this study is a Phase III trial, with Substudy A enrolling approximately 820 participants and Substudy B enrolling approximately 618 participants. Again, based on your disease pathology type, the investigator will determine your enrollment into either substudy. Eligible participants will be randomly assigned to one of two treatment groups in a 1:1 ratio (similar to flipping a coin or drawing names from a hat), giving each participant an equal 1/2 chance of being assigned to either group. In each substudy, approximately half of the participants will receive HLX37 at dose selected combined with chemotherapy, and the other half will receive pembrolizumab at 200 mg combined with chemotherapy. Both treatment groups will follow a Q3W treatment schedule.

Primary objective is to evaluate the efficacy of different doses of HLX37 in combination with chemotherapy vs. pembrolizumab in combination with chemotherapy as first-line therapy in participants with advanced non-small cell lung cancer (NSCLC).

Secondary objectives includes:

  • To evaluate the safety of HLX37 in combination with chemotherapy vs. pembrolizumab in combination with chemotherapy as first-line therapy in participants with advanced NSCLC
  • To evaluate the pharmacokinetic (PK) profile of HLX37
  • To evaluate the immunogenicity of HLX37
  • To evaluate the relationship between PD-L1 expression in tumor tissues and efficacy
02

Conditions studied

  • NSCLC (Advanced Non-small Cell Lung Cancer)

Keywords

  • NSCLC
  • Bispecific Antibody
  • Anti-angiogenesis
  • Immunotherapy
03

In context

Carcinoma, Non-Small-Cell Lung

6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.

This study's planned enrollment of 1,438 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Shanghai Henlius Biotech is the lead sponsor of 128 studies on the registry; 54 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Days to 75 Days
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF); voluntarily participate in the study; be able to complete the study as per protocol requirements; 2. Aged ≥ 18 years and ≤ 75 years at the time of signing the ICF, male or female; 3. Life expectancy ≥ 3 months; 4. An ECOG performance status score of 0-1 within 7 days prior to the first dose; 5. Histologically or cytologically confirmed, locally advanced (stage IIIB/IIIC) or metastatic(stage IV) NSCLC not eligible for radical treatment (complete surgical resection, concurrent/sequential radiochemotherapy) according to the Union for International Cancer Control and the American Joint Committee on Cancer (AJCC) TNM staging system for lung cancer (8th edition); Note: For participants with locally advanced (stage IIIB/IIIC) disease not eligible for radical concurrent/sequential radiochemotherapy, a documented evaluation by a specialist is required.

    6. Absence of known sensitizing EGFR mutations or ALK, ROS1, NTRK, BRAF, MET14 exon skipping or targetable RET driver gene alterations. Participants with nsq-NSCLC or those with sq-NSCLC who have never smoked must provide previous tissue specimen test results confirming negative EGFR, ALK, and other related gene alterations; otherwise, tumor tissue samples should be provided for relevant tests at the study site. For participants with sq-NSCLC who have a previous or current smoking history, if EGFR and/or ALK and other related gene statuses are unknown, the relevant tests are not required before enrollment in this study; 7. Agree to provide archived tumor tissue specimens that meet the testing requirements (from the most recent surgery or biopsy, preferably within half a year before randomization) or agree to undergo a biopsy to collect tumor tissue for PD-L1 expression testing;Have not previously received systemic anti-tumor therapy for advanced or metastatic NSCLC; participants who have received adjuvant or neoadjuvant therapy are eligible for this study if the adjuvant/neoadjuvant therapy had been completed at least 6 months before the diagnosis of locally advanced/recurrent or distant metastatic NSCLC; 9. At least one measurable lesion by central imaging as per RECIST v1.1 within 4 weeks before the first dose, which is suitable for repeated measurement; note: previously irradiated lesions cannot be used as the target lesions; 10. The first dose of the study treatment should be at least 28 days apart from any previous major surgery, medical device treatment, and local radiotherapy (except palliative radiotherapy for bone lesions), at least 2 weeks apart from any previous non-specific immunomodulatory treatment (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 for platelets decreased), at least 7 days apart from any previous treatment with traditional Chinese medicine for anti-tumor indications, and at least 1 year apart from any previous treatment with immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, and the last dose of any anti-angiogenic agents; any treatment-induced AEs should resolve to Grade ≤ 1 as per CTCAE v6.0 (except for alopecia);

Exclusion criteria

Exclusion Criteria:

  • NSCLC with small cell lung cancer or neuroendocrine carcinoma confirmed by tumor histology or cytology; 2. History of other malignant tumors within 3 years prior to the first dose of the study treatment, except cured cervical carcinoma in situ or cutaneous basal cell carcinoma; 3. History of AEs leading to permanent discontinuation of immunotherapy, or history of Grade ≥ 2 immune-related pneumonitis or immune-related myocarditis; 4. History of (non-infectious) interstitial lung disease (ILD) with current need for steroid treatment; or currently active ILD, or suspected risk of ILD aggravation or unsuitability for participation in this study as considered by the investigator via imaging at screening; 5. History of severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or known allergy to any components in the investigational drug formulation; known allergy to any components of carboplatin, paclitaxel, albumin-bound paclitaxel, or pemetrexed. Participants are allowed to be enrolled if they are only allergic to either paclitaxel or albumin-bound paclitaxel, in whom the use of the other paclitaxel preparation is safe as assessed by the investigator; 6. Active systemic infectious diseases (such as those requiring antibiotic treatment) within 2 weeks before the first dose; 7. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 8. Clinically symptomatic and uncontrolled pleural effusion, pericardial effusion, or ascites; 9. Having received thoracic radiotherapy > 30 Gy within 6 months prior to randomization; having received non-thoracic radiotherapy > 30 Gy within 4 weeks prior to randomization or palliative radiotherapy ≤ 30 Gy within 1 week prior to randomization; 10. Imaging evidence of the following during the screening period: a. tumor invasion into large blood vessels or important organs (such as main bronchus) or risk of tracheoesophagealfistula or esophagopleural fistula; b. tumor encapsulation of large blood vessels with vascular stenosis, or cavitation or necrosis of lung lesions, which will lead to the risk of bleeding should the participant be enrolled in the study, as assessed by the investigator; 11. Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or left ventricular ejection fraction (LVEF) \< 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except lacunar infarction, slight cerebral ischemia, or transient ischemic attack); (4) poorly controlled arrhythmia (including QTc intervals ≥ 450 ms for males and ≥ 470 ms for females) (QTc intervals are calculated by Fridericia's formula); 12. Occurrence of the following diseases within 12 months before the first dose: history of varicose veins in the lower esophagus, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, abdominal abscess, or acute gastrointestinal bleeding; occurrence of the following diseases within 6 months before the first dose: any arterial thromboembolic events, NCI CTCAE v6.0 Grade 3 or greater venous thromboembolism, transient ischemic attack, cerebrovascular accident, hypertensive crisis, history of hypertensive encephalopathy, or history of acute exacerbation of chronic obstructive pulmonary disease; current hypertension with a systolic blood pressure of ≥ 150 mmHg or a diastolic blood pressure of ≥ 100 mmHg after treatment with oral antihypertensive drugs;
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Care provider, Investigator, Outcomes assessor)
Enrollment
1,438 participants (estimated)

Study arms

  • Experimental
    nsq-NSCLC-Arm1

    HLX37 dose1 + chemotherapy, Q3W

    Drug: Investigational drug: HLX37 dose1, IV, Q3W · Drug: Carboplatin (Investigator discretion) · Drug: Pemetrexed (1)

  • Experimental
    nsq-NSCLC-Arm2

    HLX37 dose2 + chemotherapy, Q3W

    Drug: Carboplatin (Investigator discretion) · Drug: Pemetrexed (1) · Drug: Investigational drug: HLX37 dose2, IV, Q3W

  • Placebo comparator
    nsq-NSCLC-Arm3

    Pembrolizumab 200 mg + chemotherapy, Q3W

    Drug: PEMBROLIZUMAB (alone or when added to a regimen above) · Drug: Carboplatin (Investigator discretion) · Drug: Pemetrexed (1)

  • Experimental
    sq-NSCLC-Arm1

    HLX37 dose1 + chemotherapy, Q3W

    Drug: Investigational drug: HLX37 dose1, IV, Q3W · Drug: Carboplatin (Investigator discretion) · Drug: Paclitaxel or Nab-Paclitaxel

  • Experimental
    sq-NSCLC-Arm2

    HLX37 dose2 + chemotherapy, Q3W

    Drug: Carboplatin (Investigator discretion) · Drug: Paclitaxel or Nab-Paclitaxel · Drug: Investigational drug: HLX37 dose2, IV, Q3W

  • Placebo comparator
    sq-NSCLC-Arm3

    Pembrolizumab 200 mg + chemotherapy, Q3W

    Drug: PEMBROLIZUMAB (alone or when added to a regimen above) · Drug: Carboplatin (Investigator discretion) · Drug: Paclitaxel or Nab-Paclitaxel

Interventions

  • DrugInvestigational drug: HLX37 dose1, IV, Q3W

    HLX37: HLX37 will be given at dose1 in Stage I via intravenous (IV) infusion once every 3 weeks (Day 1 \[D1\] of each cycle). HLX37 will be given in Stage II at a dose to be determined based on Stage I study results via IV infusion once every 3 weeks (D1 of each cycle).

  • DrugPEMBROLIZUMAB (alone or when added to a regimen above)

    Pembrolizumab: Pembrolizumab will be given at a flat dose of 200 mg via IV infusion once every 3 weeks (D1).

  • DrugCarboplatin (Investigator discretion)

    Carboplatin: AUC = 5 up to a dose of 750 mg, or AUC = 6 up to a dose of 900 mg, based on local treatment guidelines, IV, once every 3 weeks (D1), given over 15-60 min.

  • DrugPaclitaxel or Nab-Paclitaxel

    Paclitaxel: 175 mg/m2 or 200 mg/m2, based on local treatment guidelines, IV, once every 3 weeks (D1), given continuously over no less than 3 h. All participants should be pretreated with oral or intravenous steroids and antihistamines according to the local approved product label and/or standard practice. Other pretreatment medications should be administered per standard practice. Nab paclitaxel: 100 mg/m2, IV, on D1, D8, and D15 of each 3-week cycle, given continuously over no less than 30 min.

  • DrugPemetrexed (1)

    Pemetrexed: 500 mg/m2, IV, on D1 of each 3-week cycle, given continuously over no less than 10 min.

  • DrugInvestigational drug: HLX37 dose2, IV, Q3W

    HLX37 will be given at dose2 (treatment group 2) in Stage I via intravenous (IV) infusion once every 3 weeks (Day 1 \[D1\] of each cycle). HLX37 will be given in Stage II at a dose to be determined based on Stage I study results via IV infusion once every 3 weeks (D1 of each cycle).

06

What researchers measure

Primary outcomes

  1. PFS assessed by BICR (Phase2&3)

    Description: Defined as the time from randomization to the first documentation of PD (RECIST v1.1) or death due to any cause (whichever occurs first)

    Time frame: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months

  2. ORR assessed by BICR (phse2)

    Defined as the proportion of participants who achieve a best overall response of CR or PR

    Time frame: From date of the first dose of study drug until the date of death from any cause, assessed up to 24months

  3. OS (phase3)

    OS (Phase3):Defined as the time from randomization to death due to any cause Time Frame: Assessed up to appoximately 50 months from enrollment

    Time frame: From date of the first dose of study drug until the date of death from any cause, assessed up to 50 months

Secondary outcomes

  1. DOR

    Defined as the time from the first documented objective response to PD or death

    Time frame: Assessed up to appoximately 35 months from enrollment

  2. ORR assessed by investigator

    Defined as the proportion of participants who achieve a best overall response of CR or PR

    Time frame: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months

  3. PFS assessed by investigator

    Defined as the time from randomization to the first documentation of PD (RECIST v1.1) or death due to any cause (whichever occurs first)

    Time frame: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months

  4. DCR

    defined as the proportion of participants who achieve a best overall response of CR or PR or an SD lasting for 12 weeks

    Time frame: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months

  5. Incidence of adverse events

    Incidence of adverse events

    Time frame: Assessed up to appoximately 42 months from enrollment

07

Study locations

16 sites
  • Anhui Medical University - The Second Hospital
    Hefei, Anhui, China
  • Beijing Cancer Hospital
    Beijing, Beijing Municipality 100000, China
  • Chongqing University Cancer Hospital
    Chongqing, Chongqing Municipality 400030, China
  • Guangxi Medical University Affiliated Tumor Hospital
    Nanning, Guangxi, China
  • Affiliated Hospital of Zunyi Medical University
    Zunyi, Guizhou 563000, China
  • Fourth Hospital of Hebei Medical University,
    Shijiazhuang, Hebei 050011, China
  • Affiliated Tumor Hospital of Harbin Medical University
    Harbin, Heilongjiang, China
  • Harbin Medical University - Tumor Hospital (The Third Affiliated Hospital)
    Harbin, Heilongjiang, China
  • Anyang Cancer Hospital
    Anyang, Henan 455100, China
  • Henan Cancer Hospital & Affiliated Cancer Hospital of Zhengzhou University
    Zhenzhou, Henan, China
  • Hubei Cancer Hospital
    Wuha, Hubei, China
  • Affiliated Hospital of Xuzhou Medical University
    Xuzhou, Jiangsu, China
  • Affiliated Zhongshan Hospital of Dalian University
    Dalian, Liaoning 116001, China
  • Affiliated Hospital of Qingdao University
    Qingdao, Shandong 266031, China
  • Cancer Hospital Affiliated to Shandong First Medical University
    Jinan, Shangdong 250117, China
  • Guangdong Provincial People's Hospital
    Guangzhou, China
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

1 registry update since Sep 25, 2026
Registered
First appeared on the registry. No changes since
Oct 8, 2026
Show all 1 update
  1. Oct 8, 2026
    First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07865910
Lead sponsor
Shanghai Henlius Biotech
Responsible party
Sponsor
First posted
Oct 8, 2026
Start date
Nov 30, 2026 (estimated)
Primary completion
Dec 30, 2030 (estimated)
Completion
Dec 30, 2031 (estimated)
Last update
Oct 8, 2026

Study contacts

Li ya Wan
Contact
Liya_Wan@henlius.com
02122200000

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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