Squamous Non-small Cell Lung Cancer
Conditions
Keywords
HB0025, sq-NSCLC, Fiest Line treatment
Brief summary
This study is a randomized, controlled, double-blind, multi-center phase III registration clinical trial, aiming to observe, compare and evaluate the efficacy and safety of HB0025 combined with paclitaxel + carboplatin compared with pembrolizumab combined with paclitaxel + carboplatin as the first-line treatment for locally advanced or metastatic squamous NSCLC. The study subjects are patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) who have not received systemic anti-tumor treatment before. The study will use the PFS evaluated by BICR as the primary endpoint, and plan to enroll approximately 480 subjects, with the proportion of locally advanced subjects not exceeding 10%. The subjects were fully informed and signed the informed consent form. If they met the inclusion criteria but did not meet the exclusion criteria, they were randomly assigned in a 1:1 ratio to receive HB0025 combined with chemotherapy Paclitaxel plus Platinum (experimental group) or pembrolizumab combined with chemotherapy Paclitaxel plus Platinum (control group). Both were administered once every 3 weeks (Q3W). After 4 cycles of treatment, Enter HB0025 or pembrolizumab monotherapy maintenance treatment (Q3W) until the investigator determines that there is no longer any clinical benefit (based on the RECIST v1.1 imaging assessment and comprehensive clinical symptom assessment by the investigator), intolerable toxicity occurs, 24 months of study treatment is completed, or other treatment termination criteria in the protocol are met. Whichever occurs first shall prevail.
Detailed description
The random stratification factors of this study are as follows: * Disease stage: ⅢB/ⅢC stage vs Ⅳ stage; * PD-L1 expression score indicator (tumor cell positive proportion score TPS): \<1%, 1%-49%, ≥50%; * Hepatic metastasis or brain metastasis: Yes vs No. This study uses the RECIST v1.1 standard to conduct regular tumor response assessments for the subjects. Tumor assessment are conducted at the 6th week (±7 days), the 12th week (±7 days), and every 9 weeks thereafter (±7 days) within 48 weeks after the first administration of the drug; and every 12 weeks thereafter (±7 days). If the subject stops the study treatment due to reasons other than disease progression or death, the tumor assessment should continue according to the fixed schedule until imaging progression or termination of the study (the latter occurring is the criterion), initiation of new anti-tumor treatment, loss to follow-up, death, withdrawal of informed consent, or study completion, whichever occurs first. After the first imaging progression, if the investigator believes that the subject can still benefit from continued treatment and meets the criteria listed in the protocol for continuing treatment, the subject can continue with the original treatment plan until no clinical benefit is observed (assessed by the investigator). If the subject stops the study treatment for reasons other than the above (such as occurrence of intolerable adverse events, or the subject has received 24 months of HB0025 or pembrolizumab treatment, or other reasons for stopping treatment, etc.), a tumor assessment should be conducted before terminating the study. The investigator can conduct unplanned (with an interval of at least 4 weeks greater than the previous assessment) tumor assessments in cases of suspected disease progression or other necessary circumstances. The sponsor will collect all the imaging data of the subjects for BICR assessment.
Interventions
DRUGCarboplatin Injection
10mL:100mL, Q3W
DRUGPaclitaxel Injection
5ml:30mg, Q3W
Sponsors
Shanghai Huaota Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
It is planned to enroll approximately 480 subjects, and they will be randomly divided into groups at a ratio of 1:1. The treatment is administered once every 3 weeks (Q3W). After 4 cycles of treatment, patients will proceed to receive maintenance therapy with HB0025 or pembrolizumab alone (also Q3W). Experimental group: HB0025 combined with chemotherapy Paclitaxel plus Platinum; Control group: pembrolizumab combined with chemotherapy Paclitaxel plus Platinum.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1. 3. Expected survival ≥ 12 weeks. 4. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) 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 \[AJCC\]) that is inoperable for radical resection and ineligible for radical concurrent/sequential chemoradiotherapy or immunotherapy as consolidation treatment. Note: For subjects with locally advanced (Stage IIIB/IIIC) NSCLC who are inoperable for radical resection and ineligible for radical concurrent/sequential chemoradiotherapy or immunotherapy as consolidation treatment, an assessment by relevant specialist physicians and provision of written documentation are required for confirmation. 6\. No previous systemic anti-tumor treatment for locally advanced or metastatic squamous NSCLC \[For subjects who have received adjuvant/neoadjuvant therapy for the purpose of cure for non-metastatic disease or radical concurrent/sequential chemoradiotherapy for locally advanced disease (including subjects receiving PD-1/L1 inhibitors), If disease progression occurs more than 12 months after the end of the last treatment, one is eligible to participate in this study. 7\. 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. 8\. 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. 9\. At least one measurable (non-brain metastatic) lesion per RECIST v1.1 criteria, which is suitable for repeated and accurate measurement. Tumor lesions previously treated with radiotherapy or other local therapies cannot be designated as target lesions, unless: * The lesion is the only measurable lesion, and the investigator can provide imaging evidence (before and after local treatment) confirming clear disease progression of the lesion after local treatment; * The lesion used for fresh tissue biopsy is the only measurable lesion. 10. Confirmed adequate organ function, as evidenced by meeting the following laboratory parameters: 1) Hematology (no receipt of blood component transfusion or hematopoietic growth factor support within 14 days before screening tests): 1. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; 2. Platelet Count (PLT) ≥ 100 × 10⁹/L; 3. Hemoglobin (HGB) ≥ 90 g/L; 2) Renal function: a) Serum Creatinine (Scr) ≤ 1.5 × Upper Limit of Normal (ULN), and Creatinine Clearance (Ccr) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula); b) Urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein excretion must be \< 1 g; 3) Hepatic function: 1. Serum Total Bilirubin (TBiL) ≤ 1.5 × ULN; 2. Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN; for subjects with liver metastasis, ALT and AST ≤ 5 × ULN; 3. Serum Albumin (ALB) ≥ 30 g/L; 4) Coagulation function: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and International Normalized Ratio (INR) ≤ 1.5 × ULN (for subjects receiving anticoagulant therapy, the investigator must confirm that INR, APTT, and PT are within the safe and effective therapeutic range); 5) Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥ 50% 11. The toxicity of previous treatment has been restored to grade 0 or 1 of NCI CTCAE version 5.0, or the level specified in the inclusion/
Exclusion criteria
(except for alopecia). Note: For subjects who experience irreversible toxicity and whose condition is not expected to worsen after administration of the study drug (such as those with hearing loss), they may be included in the study after consultation with medical monitors. 12\. Female and male subjects of childbearing potential must agree to use effective contraceptive measures from the screening period until 90 days after the last dose of study treatment. Discussion with the investigator is required to determine whether contraception can be discontinued after this period. Female subjects must not be breastfeeding. Female subjects of childbearing potential must have a negative serum pregnancy test result within 7 days before randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to approximately 24 Months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 24 Months | OS is defined as the period from the start of randomization to the time of death due to any cause according to RECIST 1.1. |
| Objective Response Rate (ORR) | Up to 24 Months | ORR is defined as the proportion of subjects achieving the best overall therapeutic effect (BOR) as complete remission (CR) or partial remission (PR) according to RECIST 1.1 by investigator. |
| Disease control rate (DCR) | Up to 24 Months | DCR defined as the number of patients were confirmed CR and/or PR and/or stable disease(SD) according to RECIST 1.1 by investigator divided by the patients with at least one tumour evaluation |
| Duration of response (DOR) | Up to 24 Months | DOR is defined as the time from the first record of CR or PR to the first record of disease. DOR as evaluated by investigators according to RECIST v1.1. |
| Time to Progression(TTP) | Up to 24 Months | TTP is defined as the time from the time of randomization to the occurrence of disease progression according to recist 1.1 by investigator. |
| Objective Response Rate (ORR)-BICR | Up to 24 Months | ORR is defined as the proportion of subjects achieving the best overall therapeutic effect (BOR) as complete remission (CR) or partial remission (PR) according to RECIST 1.1 by BICR |
| Disease control rate (DCR)-BICR | Up to 24 Months | DCR defined as the number of patients were confirmed CR and/or PR and/or stable disease(SD) according to RECIST 1.1 by BICR divided by the patients with at least one tumour evaluation |
| Duration of response (DOR)-BICR | Up to 24 Months | DOR is defined as the time from the first record of CR or PR to the first record of disease. DOR as evaluated by BICR according to RECIST v1.1 |
| Time to Progression(TTP)-BICR | Up to 24 Months | TTP is defined as the time from the time of randomization to the occurrence of disease progression according to recist 1.1 by BICR |
| Safety Assement | Up to 24 Months | The incidence, severity and outcome of adverse events (AE), serious adverse events (SAE), immune-related adverse events (irAE) and adverse events of special concern (AESI) per NCI-CTCAE V5.0 |
| Maximum serum concentration(Cmax) | Up to 24 Months | Cmax refers to The maximum blood concentration of HB0025 after administration. - Sample concentration analysis method adopts ELISA. parameters will be calculated by Phoenix WinNonlin version 8.3. |
| Anti-drug antibodies (ADA) | Up to 24 Moths | Incidence of positive anti-drug antibodies(ADA). |
Countries
China
Contacts
CONTACTCaicun Zhou
Outcome results
None listed