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
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:
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 →Shanghai Henlius Biotech is the lead sponsor of 128 studies on the registry; 54 are open to participants now.
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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:
HLX37 dose1 + chemotherapy, Q3W
Drug: Investigational drug: HLX37 dose1, IV, Q3W · Drug: Carboplatin (Investigator discretion) · Drug: Pemetrexed (1)
HLX37 dose2 + chemotherapy, Q3W
Drug: Carboplatin (Investigator discretion) · Drug: Pemetrexed (1) · Drug: Investigational drug: HLX37 dose2, IV, Q3W
Pembrolizumab 200 mg + chemotherapy, Q3W
Drug: PEMBROLIZUMAB (alone or when added to a regimen above) · Drug: Carboplatin (Investigator discretion) · Drug: Pemetrexed (1)
HLX37 dose1 + chemotherapy, Q3W
Drug: Investigational drug: HLX37 dose1, IV, Q3W · Drug: Carboplatin (Investigator discretion) · Drug: Paclitaxel or Nab-Paclitaxel
HLX37 dose2 + chemotherapy, Q3W
Drug: Carboplatin (Investigator discretion) · Drug: Paclitaxel or Nab-Paclitaxel · Drug: Investigational drug: HLX37 dose2, IV, Q3W
Pembrolizumab 200 mg + chemotherapy, Q3W
Drug: PEMBROLIZUMAB (alone or when added to a regimen above) · Drug: Carboplatin (Investigator discretion) · Drug: Paclitaxel or Nab-Paclitaxel
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: Pembrolizumab will be given at a flat dose of 200 mg via IV infusion once every 3 weeks (D1).
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: 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: 500 mg/m2, IV, on D1 of each 3-week cycle, given continuously over no less than 10 min.
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).
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
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
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
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
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
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
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
Incidence of adverse events
Incidence of adverse events
Time frame: Assessed up to appoximately 42 months from enrollment
Plan to share: No
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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 ↗
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Shanghai Henlius Biotech