Non-Small Cell Lung Cancer
Conditions
Brief summary
This is a multicenter, open-label, Phase 1 clinical study to evaluate the efficacy and safety of HS-20093 combination therapy in subjects with advanced or metastatic non-small cell lung cancer without actionable genomic alterations.
Detailed description
This is a multicenter, open-label, Phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of HS-20093 combination therapy in subjects with advanced non-small cell lung cancer (NSCLC). The study is divided into Phase 1a (safety run-in) and Phase 1b (cohort expansion). In Phase 1a, the safety and tolerability of HS-20093 in combination with ivonescimab (± chemotherapy) will be evaluated in subjects with advanced NSCLC. After the preliminary evaluation of the safety results of Phase 1a by the Safety Review Committee (SRC), the study will proceed to Phase 1b, with randomized enrollment, to explore different treatment strategies of the combination regimens.
Interventions
DRUGHS-20093
Participants will receive intravenous infusions of HS-20093 and ivonescimab. HS-20093 will be administered at the pre-specified dose level(s) Q3W , until disease progression or other treatment discontinuation criteria are met.
DRUGIvonescimab
Participants will receive intravenous infusions of HS-20093 and ivonescimab. Ivonescimab will be administered at at 20 mg/kg Q3W, until disease progression or other treatment discontinuation criteria are met.
DRUGChemotherapy
Participants will receive intravenous infusions of pemetrexed or nab-paclitaxel, all administered every 3 weeks (Q3W) until disease progression or other treatment discontinuation criteria are met. Pemetrexed at 500 mg/m², or nab-paclitaxel at 100 mg/m²per Q3W cycle.
Sponsors
Hansoh BioMedical R&D Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years at the time of informed consent form (ICF) signature, either sex. 2. Be willing to participate in this clinical trial with understanding of study procedures, ability to provide written informed consent, and commitment to comply with all requirements specified in this clinical trial protocol. 3. Previously untreated patients with histologically or cytologically confirmed diagnosis of advanced or metastatic non-small cell lung cancer (NSCLC) without actionable driver mutations 4. Presence of at least one measurable target lesion. 5. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1. 6. Minimum life expectancy \>12 weeks. 7. Adequate organ function. 8. Absence of the following active infectious diseases: hepatitis B, hepatitis C, human immunodeficiency virus (HIV) infection, tuberculosis, or syphilis. 9. Female participants with negative serum pregnancy test result within 7 days prior to first dose administration, or documentation of no pregnancy risk.
Exclusion criteria
1. Prior pathological diagnosis of mixed non-small cell lung cancer or any transformed non-small cell lung cancer. 2. Presence of any of the following abnormal cardiac findings: 1\) Evidence of currently clinically significant important arrhythmia or ECG abnormality; 2) Presence of risk factors causing QT interval prolongation or arrhythmic events. 3\. Untreated or uncontrolled brain metastases, leptomeningeal disease, brainstem metastases, or spinal cord compression. 4\. Severe, uncontrolled, or active cardiovascular or cerebrovascular disease. 5. Severe or poorly controlled hypertension and/or diabetes mellitus. 6. Has experienced ≥ grade 2 bleeding events 7. Persistent adverse reactions caused by prior treatment. 8. History of other primary malignancies. 9. Severe infection. 10. History of severe arterial or venous thromboembolic events. 11. Known or suspected interstitial pneumonitis, immune-mediated pneumonitis, or radiation pneumonitis. 12\. Participants with active or history of autoimmune disease with potential for recurrence. 13\. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 14\. Pregnant or breastfeeding, or planning to breastfeed during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at phase 1b | From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 48 months. | ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigators based on RECIST version 1.1\[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\]. |
| Phase 1a: Dose-Limiting Toxicity (DLT) | Through out the DLT period, approximately 21 days | Evaluate the number of patients with dose-limited toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) determined by investigators according to RECIST 1.1 | From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 48 months. | DoR was defined as the period from the first occurrence of CR or PR to progressive disease (PD) or death from any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) would be used \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\]. |
| Disease control rate (DCR) determined by investigators according to RECIST 1.1. | From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 48 months. | Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). DCR was evaluated by the number of participants with best overall response of CR, PR and stable disease (SD) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\]. |
| Progression-free survival (PFS) determined by investigators according to RECIST 1.1 | From the first dose or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 48 months. | Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). PFS was defined as the time from first dose or random assignment (if any) to PD or death from any cause. |
| Overall survival (OS) | From the first dose or random assignment up to death or withdrawal from study, whichever came first, assessed up to 48 months. | OS was defined as the time from the first dose or random assignment (if any) to death from any cause. |
| Observed maximum plasma concentration (Cmax) of HS-20093 | Till study completion, approximately 48 months. | Cmax will be obtained following administration of the first dose of HS-20093 during the first cycle. |
| Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093 | Till study completion, approximately 48 months. | Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration was no less than the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. |
| Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose | Till study completion, approximately 48 months. | Tmax will be obtained following administration of the first dose of HS-20093 during the first cycle |
| Incidence and severity of adverse events (AEs) | From the first dose through 90 days post end of treatment. | AE assessed by investigator exclusively related to subject's underlying disease or medical condition \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\]. Any untoward medical occurrence in a clinical study participant, whether or not considered related to the medicinal product. Incidence and severity of AEs are assessed according to vital signs, laboratory variables, electrocardiogram, etc. |
Outcome results
None listed