NSCLC (Advanced Non-small Cell Lung Cancer)Phase 2/3NCT07865910
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 study testing Investigational drug: HLX37 dose1, IV, Q3W, PEMBROLIZUMAB (alone or when added to a regimen above) and Carboplatin (Investigator discretion) in people with NSCLC (Advanced Non-small Cell Lung Cancer), run by Shanghai Henlius Biotech at 16 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 days
- Conditions the study is for
- NSCLC (Advanced Non-small Cell Lung Cancer)
- What is being tested?
- Investigational drug: HLX37 dose1, IV, Q3W, PEMBROLIZUMAB (alone or when added to a regimen above) and Carboplatin (Investigator discretion)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,438 participants
- Where
- 16 sitesChina
- Study dates
- 30 Nov 2026to 30 Dec 2031
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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);
Who cannot join
- 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;
Trial locations and contacts
16 sites in 1 country. Contact the study team or a site near you to ask about taking part.
16 sites in 1 country
China16 sites
Anyang Cancer Hospital
Anyang, Henan, 455100
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100000
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, 400030
Affiliated Zhongshan Hospital of Dalian University
Dalian, Liaoning, 116001
Guangdong Provincial People's Hospital
Guangzhou
Affiliated Tumor Hospital of Harbin Medical University
Harbin, Heilongjiang
Harbin Medical University - Tumor Hospital (The Third Affiliated Hospital)
Harbin, Heilongjiang
Anhui Medical University - The Second Hospital
Hefei, Anhui
Cancer Hospital Affiliated to Shandong First Medical University
Jinan, Shangdong, 250117
Lin lin Wang, Dr, +86 0531-67626971, wanglinlinatjn@163.com
Ming Jin Yu, PHD, wanglinlinatjn@163.com
Guangxi Medical University Affiliated Tumor Hospital
Nanning, Guangxi
Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266031
Fourth Hospital of Hebei Medical University,
Shijiazhuang, Hebei, 050011
Hubei Cancer Hospital
Wuha, Hubei
Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu
Henan Cancer Hospital & Affiliated Cancer Hospital of Zhengzhou University
Zhenzhou, Henan
Affiliated Hospital of Zunyi Medical University
Zunyi, Guizhou, 563000
About this study
Official title: 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
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.
Read more
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
- Being tested
- Investigational drug: HLX37 dose1, IV, Q3W, PEMBROLIZUMAB (alone or when added to a regimen above), Carboplatin (Investigator discretion), Paclitaxel or Nab-Paclitaxel, Pemetrexed (1)
- Keywords
- NSCLC, Bispecific Antibody, Anti-angiogenesis, Immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Investigational drug: HLX37 dose1, IV, Q3WDrug
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).
PEMBROLIZUMAB (alone or when added to a regimen above)Drug
Pembrolizumab: Pembrolizumab will be given at a flat dose of 200 mg via IV infusion once every 3 weeks (D1).
Carboplatin (Investigator discretion)Drug
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.
Paclitaxel or Nab-PaclitaxelDrug
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.
Pemetrexed (1)Drug
Pemetrexed: 500 mg/m2, IV, on D1 of each 3-week cycle, given continuously over no less than 10 min.
Investigational drug: HLX37 dose2, IV, Q3WDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| nsq-NSCLC-Arm1 | Experimental | HLX37 dose1 + chemotherapy, Q3W Receives: Drug: Investigational drug: HLX37 dose1, IV, Q3W; Drug: Carboplatin (Investigator discretion); Drug: Pemetrexed (1) |
| nsq-NSCLC-Arm2 | Experimental | HLX37 dose2 + chemotherapy, Q3W Receives: Drug: Carboplatin (Investigator discretion); Drug: Pemetrexed (1); Drug: Investigational drug: HLX37 dose2, IV, Q3W |
| nsq-NSCLC-Arm3 | Placebo comparator | Pembrolizumab 200 mg + chemotherapy, Q3W Receives: Drug: PEMBROLIZUMAB (alone or when added to a regimen above); Drug: Carboplatin (Investigator discretion); Drug: Pemetrexed (1) |
| sq-NSCLC-Arm1 | Experimental | HLX37 dose1 + chemotherapy, Q3W Receives: Drug: Investigational drug: HLX37 dose1, IV, Q3W; Drug: Carboplatin (Investigator discretion); Drug: Paclitaxel or Nab-Paclitaxel |
| sq-NSCLC-Arm2 | Experimental | HLX37 dose2 + chemotherapy, Q3W Receives: Drug: Carboplatin (Investigator discretion); Drug: Paclitaxel or Nab-Paclitaxel; Drug: Investigational drug: HLX37 dose2, IV, Q3W |
| sq-NSCLC-Arm3 | Placebo comparator | Pembrolizumab 200 mg + chemotherapy, Q3W Receives: Drug: PEMBROLIZUMAB (alone or when added to a regimen above); Drug: Carboplatin (Investigator discretion); Drug: Paclitaxel or Nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months
ORR assessed by BICR (phse2)
Defined as the proportion of participants who achieve a best overall response of CR or PR
Measured: From date of the first dose of study drug until the date of death from any cause, assessed up to 24months
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
Measured: From date of the first dose of study drug until the date of death from any cause, assessed up to 50 months
Secondary outcomes (5)
DOR
Defined as the time from the first documented objective response to PD or death
Measured: Assessed up to appoximately 35 months from enrollment
ORR assessed by investigator
Defined as the proportion of participants who achieve a best overall response of CR or PR
Measured: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months
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)
Measured: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months
DCR
defined as the proportion of participants who achieve a best overall response of CR or PR or an SD lasting for 12 weeks
Measured: From date of the first dose of study drug until the date of death from any cause, assessed up to 24 months
Incidence of adverse events
Incidence of adverse events
Measured: Assessed up to appoximately 42 months from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2026
- Study start30 Nov 2026 (estimated)
- Primary completion30 Dec 2030 (estimated)
- Study completion30 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC (Advanced Non-small Cell Lung Cancer)Studies of the same condition, open and under way.
- More trials run by Shanghai Henlius BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,438 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Henlius Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07865910
- Sponsor's protocol ID
- HLX37- NSCLC301
- Status last verified
- Oct 2026
- First submitted
- 4 Oct 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No