A Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in Patients With Advanced Non-small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Ningetinib
- Conditions
- Stage IV Non-small Cell Lung Cancer
- Sponsor
- Jiangsu Alphamab Biopharmaceuticals Co., Ltd
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase II, open label, multicenter study in subjects with advanced non-small cell lung cancer.
Detailed Description
A Phase 2 Clinical Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in Subjects with Advanced Non-small Cell Lung Cancer
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed inform consent form(ICF);
- •Age ≥ 18 years and ≤ 75 years, male or female;
- •Histologically or cytologically documented NSCLC,Stage IV (AJCC Version 8) .
- •At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1;
- •Biopsy specimens obtained from nonradiated areas within 1 year, formalin-fixed, paraffin-embedded blocks containing tumor tissues suitable for biomarker determination, or 15-20 slides (more slides are encouraged to be provided with a minimum of 8 slides; if less than 8 slides are provided, the subject may also be enrolled after consultation and agreement between the Sponsor and the investigator); and fresh biopsy samples collected within 42 days prior to the first dose are required for determination in Cohorts C, D, and E;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Life expectancy \> 12 weeks;
- •Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed.
- •Ability to comply with treatment, procedures and pharmacokinetics (PK) sample collection and the required study follow-up procedures
Exclusion Criteria
- •Known brain metastasis or another Central Nervous System (CNS) metastasis that is either symptomatic or untreated.
- •Having participated in any interventional clinical study within 28 days prior to drug administration in this study.
- •Having received other anti-tumor therapy within 28 days before administration in this study, including traditional Chinese medicine with anti-tumor indications;
- •Having received major surgical treatment (such as major abdominal, transthoracic surgery; excluding diagnostic aspiration or peripheral vascular access replacement) within 28 days prior to drug administration in this study;
- •Having received radical radiotherapy within 3 months prior to drug administration in this study; palliative radiation therapy within 2 weeks prior to the first dose is allowed, the radiation dose meets the diagnostic and treatment criteria for local palliative treatment, and the radiation coverage is less than 30% of the bone marrow area;
- •Subjects who require systemic corticosteroids (≥ 10 mg/day prednisone or equivalent dose of other corticosteroids) or immunosuppressive therapy within 14 days prior to drug administration in this study; except for inhaled or topical corticosteroids, or physiologic replacement doses of corticosteroids for adrenal insufficiency; short-term (≤ 7 days) corticosteroids are allowed for prophylaxis (e.g., contrast media allergy) or for the treatment of non-autoimmune disorders (e.g., delayed type hypersensitivity due to contact allergens);
- •Having received live vaccines (including live attenuated vaccines) within 28 days prior to drug administration in this study;
- •Previous or current interstitial pneumonia/pneumopathy; Subjects with active autoimmune diseases or history of autoimmune diseases should be excluded.
- •Subjects who have prior or current autoimmune diseases;
- •Subjects who have other malignancies within 5 years before the first dose;
Arms & Interventions
Cohort E
≥ 2L NSCLC (failure or intolerance of 1L platinum-doublet chemotherapy; and failure of PD-1/PD-L1 checkpoint inhibitor therapy), will receive KN046 in combination with ningetinib
Intervention: Ningetinib
Cohort A
Subjects with Non-small Cell Lung Cancer (NSCLC) (failed or did not tolerant to platinum-containing regime and did not treat with programmed cell death protein 1/the programmed death-ligand 1 (PD1/PDL-1) checkpoint inhibitor previously) will receive KN046 3 milligram per kilogram (mg/kg), every other weeks (Q2W)
Intervention: KN046
Cohort B
Subjects with NSCLC (failed or did not tolerant to platinum-containing regime and did not treat with PD1/PDL-1 checkpoint inhibitor previously) will receive KN046 5 mg/kg, Q2W
Intervention: KN046
Cohort C
Subjects with NSCLC (failed or did not tolerant to platinum-containing regime and failed to PD1/PDL-1 checkpoint inhibitor) will receive KN046
Intervention: KN046
Cohort D
1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy), will receive KN046 5 mg/kg Q3W in combination with pemetrexed and carboplatin
Intervention: KN046
Cohort D
1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy), will receive KN046 5 mg/kg Q3W in combination with pemetrexed and carboplatin
Intervention: Carboplatin
Cohort D
1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy), will receive KN046 5 mg/kg Q3W in combination with pemetrexed and carboplatin
Intervention: Pemetrexed
Cohort E
≥ 2L NSCLC (failure or intolerance of 1L platinum-doublet chemotherapy; and failure of PD-1/PD-L1 checkpoint inhibitor therapy), will receive KN046 in combination with ningetinib
Intervention: KN046
Outcomes
Primary Outcomes
ORR
Time Frame: 2 years
clinical response rate (ORR) as determined by the independent review board (IRC) based on RECIST 1.1 criteria
DOR
Time Frame: 2 years
clinical response time (DOR) as determined by the independent review board (IRC) based on RECIST 1.1 criteria