SKB264 for Advanced non-small cell lung cancer | Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Subjects must be at least 18 years of age on day of signing informed consent, regardless of gender.\n- Left ventricular ejection fraction (LVEF)≥ 50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA).\n- Subjects must have recovered from all toxicities led by prior treatment (recover to < Grade 2 based on CTCAE 5.0 criteria, or to levels defined in the eligibility criteria) with the exception of toxicities not considered a safety risk (e.g. alopecia, vitiligo, and other asymptomatic laboratory abnormalities)\n- Contraceptive methods used by male and female subjects must comply with contraceptive methods of local regulations for clinical study subjects\n- Subjects should voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol- specified visits and relevant procedures.\n- Subjects with histologically or cytologically confirmed NSCLC, locally advanced (stage IIIB/IIIC) or metastatic (Stage IV) NSCLC not amenable to receive definitive surgery and/or radiotherapy (with or without concurrent chemotherapy), according to TNM staging of lung cancer published by the International Union Against Cancer and American Joint Committee on Cancer, 8th edition.\n- EGFR wild-type cohorts: for subjects with non-squamous or mixed histology NSCLC should be confirmed by tumor histology to be EGFR wild- type and ALK fusion gene negative; without known alterations of driver genes such as ROS1, NTRK, and BRAF; without actionable genomic alterations for other approved targetable therapies. For subjects with squamous NSCLC, if the prior EGFR and ALK status is unknown, the corresponding tests are not required prior to enrollment in this study and the gene status will be considered negative. EGFR mutation cohorts: subjects should be confirmed by tumor histology, cytology or blood sample to harbor EGFR exon 19 deletion mutation or exon 21 L858R mutation.\n- The study will include: a) Locally advanced or metastatic NSCLC subjects without actionable EGFR mutations and ALK fusion genes, without known ROS1, NTRK, BRAF gene alterations or other actionable gene mutation kinases with approved therapies. b) Locally advanced or metastatic NSCLC subjects without actionable EGFR mutations and ALK fusion genes, known ROS1, NTRK, BRAF gene alterations, or other actionable gene mutation kinases with approved therapies, who have not received prior systemic treatment including prior treatment with PD-1/PD-L1 antibodies. c) Subjects with EGFR exon 19 deletion mutation or exon 21 L858R, mutation who failed prior EGFR-TKI treatment, meeting all of the following criteria. d) Subjects with EGFR exon 19 deletion or exon 21 L858R mutation; no prior systemic treatment.\n- Subjects are able to provide tumor blocks or slides before the first dose of study intervention.\n- Subject must have at least one radiographically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria; brain metastatic lesion(s) will not be selected as target lesion.\n- Subject has an ECOG performance status of either 0 or 1 as assessed within 7 days before initiation of study intervention\n- Life expectancy at least 3 months for the subject\n- Adequate organ function as indicated by the laboratory values. For further details please refer to protocol."}

Exclusion criteria

• {"criterion_text":"- Subjects with mixed SCLC histopathological features\n- Subjects with uncontrolled systemic disease as judged by the Investigator: a) Subjects with uncontrolled hypertension under medication intervention (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg), history of unstable hypertension, or history of poorly compliant anti-hypertension treatment. b) Subjects with uncontrolled diabetes under medication intervention. c) Subjects with pleural effusion, pericardial effusion, or ascites that is clinically symptomatic or requires repeated drainage.\n- Subjects with active autoimmune disease that required systemic treatment in the past 2 years (e.g., use of disease symptom relieving agents, corticosteroids or immunosuppressive drugs). Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted.\n- Subjects with active hepatitis B or hepatitis C.\n- Subjects with known history of Human Immunodeficiency Virus (HIV)\n- Subjects with known active tuberculosis.\n- Subjects who have received any chemotherapy, radiotherapy, immunotherapy, or biologic therapy within 4 weeks before the first dose of study intervention; received small molecule TKIs, anti-tumor hormone therapy, systemic immune stimulators (including but not limited to interferon, and IL-2), or traditional Chinese medicine preparations approved for anti-tumor indications within 2 weeks or five half-lives prior to the first dose of study intervention; palliative radiation to known metastatic sites within 2 weeks prior to the first dose of study intervention.\n- Subjects who have received other clinical investigational drugs or major surgery within 4 weeks prior to the first dose of study intervention.\n- Subjects who have received radiation therapy to lung that is more than 30 Gy within 6 months prior to the first dose of study intervention.\n- Subjects who required the systemic use of strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks or 5 half-life periods prior to the first dose of study intervention and during the study (strong inhibitors or inducers of CYP3A4 are not permitted in this study; Appendix 7 in the protocol listed some representatives, for medication outside of the listing, investigator’s evaluation is needed).\n- Subjects who have received continuous high-dose systemic corticosteroids within 2 weeks prior to the first dose of study intervention (low-dose corticosteroids, such as ≤ CCI mg/day prednisone or equivalent, are permitted if the dose is stable for at least 4 weeks), or other immunosuppressive therapy.\n- Subjects with a known history of prior malignancy unless the subject has undergone potentially curative therapy with no evidence of that disease recurrence for 3 years since initiation of that therapy\n- Subjects who have received a live or live-attenuated vaccine within 4 weeks prior to the first dose of study intervention, or are scheduled to receive live vaccines during the study\n- Subjects with serious infections within 4 weeks prior to the first dose of study intervention (including but not limited to comorbidity, sepsis or severe pneumonia that require hospitalization) or concomitant infections requiring systemic antibiotic treatment within 2 weeks prior to the first dose of study intervention.\n- Subjects with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.\n- Known allergy or hypersensitivity to pembrolizumab, SKB264, platinum or osimertinib, or the excipients of pembrolizumab, SKB264 platinum or osimertinib, or history of severe hypersensitivity to another biologic therapy.\n- For other (24-27) please refer to protocol.\n- Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active CNS metastases.\n- Subjects with ≥ Grade 2 peripheral neuropathy.\n- Subjects with history of esophagogastric varices, severe ulcers, gastrointestinal perforation,gastrointestinal obstruction, intra-abdominal abscess, or acute gastro-intestinal bleeding within 6 months prior to the first dose of study intervention.\n- Subjects who had arteriovenous thromboembolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for venous thrombosis caused by venous catheterization in prior chemotherapy that have resolved as judged by the Investigator) and pulmonary embolism within 6 months prior to the first dose of study intervention.\tTumor invasion or encasement of surrounding vital organs and blood vessels or the risk of esophageal tracheal fistula or esophageal pleural fistula, or subjects with superior vena cava syndrome currently.\n- Subjects with active inflammatory bowel disease or previous clear history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).\n- Subjects who suffer from cardiovascular diseases of clinical significance, such as: a) Subjects who had serious or uncontrolled cardiac disease or clinical symptoms requiring treatment within 6 months prior to the first dose of the study intervention, including: congestive heart failure classified as Class III to IV by New York Heart Association(NYHA), unstable angina that cannot be controlled by medication, serious arrhythmia requiring medical treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia), myocardial infarction. b) Subjects with previous history of myocarditis, or cardiomyopathy c) Subjects with QTc interval > 480 ms at baseline;\n- Subjects with a history of interstitial lung disease (ILD)/non-infectious pneumonitis that required steroid."}

Primary endpoints

• {"endpoint_text":"- Dose-limiting toxicity (DLT)Incidence and severity of AEs Discontinuation of study treatment due to AEs","definition_or_measurement_approach":"Incidence and severity of adverse events (AEs) including dose-limiting toxicity (DLT) and treatment discontinuation due to AEs (as stated). Specific DLT definitions not provided in the available record."}
• {"endpoint_text":"- ORR per RECIST v1.1: the proportion of subjects with a confirmed complete response (CR) or partial response (PR)","definition_or_measurement_approach":"Measured per RECIST v1.1 as the proportion of subjects with confirmed complete response (CR) or partial response (PR)."}

Secondary endpoints

• {"endpoint_text":"- DOR: For subjects with a confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until radiographic disease progression or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Duration of response (DOR) defined as time from first documented CR/PR to radiographic disease progression or death from any cause, whichever occurs first."}
• {"endpoint_text":"- PFS: The time from first dose of study intervention to first documentation of radiographic disease progression or death due to any cause, whichever occurs first","definition_or_measurement_approach":"Progression-free survival (PFS) measured from first dose to first radiographic disease progression or death from any cause."}
• {"endpoint_text":"- OS: The time from first dose of study intervention to death due to any cause.","definition_or_measurement_approach":"Overall survival (OS) measured from first dose of study intervention to death due to any cause."}
• {"endpoint_text":"- PK parameters including Cmin and Cmax of SKB264-ADC, SKB264-TAB and free KL610023.","definition_or_measurement_approach":"Pharmacokinetic parameters including minimum concentration (Cmin) and maximum concentration (Cmax) for SKB264-ADC, SKB264-TAB and free KL610023."}
• {"endpoint_text":"- Anti-drug antibody (ADA) test results of SKB264.","definition_or_measurement_approach":"Immunogenicity assessed by anti-drug antibody (ADA) testing for SKB264."}

Romania

Earliest CTIS Part Ii Submission Date

16-05-2024

Latest Decision Or Authorization Date

24-03-2026

Processing Time Days

677

Number Of Sites

2

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

14-05-2026

Processing Time Days

714

Number Of Sites

9

Number Of Participants

31

Primary sponsor

Full Name

Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

China

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

codes: 1,10,11,12,13,14,2,5,6,8

Name

IQVIA Limited

Responsibilities

codes: 3

Name

Q Squared Solutions Limited

Responsibilities

codes: 4

Name

Bioclinica Shanghai Co. Ltd.

Responsibilities

codes: 6,7

Name

Frontage Laboratories Inc.

Responsibilities

codes: 4

Name

Medx (Suzhou) Translational Medicine Co. Ltd.

Responsibilities

codes: 4

Third parties

• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"codes: 1,10,11,12,13,14,2,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"codes: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"China","full_name":"Bioclinica Shanghai Co. Ltd.","duties_or_roles":"codes: 6,7","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Medx (Suzhou) Translational Medicine Co. Ltd.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}