SKB264 Monotherapy in Selected Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of SKB264 monotherapy in subjects with selected advanced solid tumors.The study is divided into two parts: the Part Ⅰ consists of 5 cohorts, and the Part Ⅱ for expansion. Eligible subjects will receive SKB264 monotherapy, until there is no longer clinical benefit, intolerable toxicity, discontinuation of study treatment required by the subject, or other protocol-specified treatment discontinuation criteria, whichever occurs first.

Detailed Description
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The second part of this study is a randomized, open-label, multicenter Phase 2 clinical study of SKB264 monotherapy versus docetaxel in subjects with locally advanced or metastatic non-squamous NSCLC.

Official Title
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A Multicenter, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of SKB264 Monotherapy in Selected Subjects With Advanced Solid Tumors

Conditions
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Selected Subjects With Advanced Solid Tumors

Intervention / Treatment
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* Drug: SKB264
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged ≥ 18 to ≤ 75 years at the time of signing the ICF; The following histologically or cytologically confirmed tumor types will be enrolled: Part Ⅰ Cohort 1, Cohort 2, Cohort 3, Cohort 5 and Part Ⅱ: histologically or cytologically confirmed Non Small Cell Lung Cancer (NSCLC); Part Ⅰ Cohort 4: histologically or cytologically confirmed nonkeratinizing differentiated or undifferentiated nasopharyngeal carcinoma (NPC) ; For subjects enrolled in Part I Cohort 1 and Part II, the following criteria must be met:①EGFR-sensitive mutations confirmed by tumor histology or cytology or hematology;②Failure of prior EGFR-TKI therapy and chemotherapy; For subjects enrolled in Part I Cohort 2, the following criteria must be met:①EGFR-sensitive mutations confirmed by tumor histology or cytology or hematology;②Failure of prior EGFR-TKI therapy;③No prior systemic therapy for locally advanced or metastatic NSCLC other than EGFR-TKI therapy; For subjects enrolled in Part I Cohort 3, the following criteria must be met: ①NSCLC confirmed by tumor histology to be EGFR wild-type and negative for ALK fusion gene; ②Subjects must have met one of the following conditions for prior systemic therapy:A. Have received platinum-based chemotherapy in combination with anti-PD-1/L1 monoclonal antibody therapy as the only prior first-line therapy;B. Have received sequential treatment with platinum-based chemotherapy and anti-PD-1/L1 monoclonal antibody (in either order) as the only prior second-line therapy; For subjects enrolled in Part I Cohort 4, the following criteria must be met: Have received prior second-line or above systemic therapies and have progressed on or after treatment, with prior therapies including platinum-based chemotherapy and anti-PD-1/PD-L1 monoclonal antibody therapy; For subjects enrolled in Part I Cohort 5, the following criteria must be met: ①The presence of other driver gene alterations confirmed by tumor histology or cytology or hematology other than EGFR-sensitive mutations ;②have failed targeted therapy for applicable genetic alterations or chemotherapy; PD as assessed by imaging on or after the most recent treatment for locally advanced or metastatic disease; Ability to provide fresh or archival tumor tissue for biomarker testing and analysis. At least one measurable target lesion per RECIST 1.1; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Expected survival ≥ 12 weeks; Adequate organ and bone marrow function; Female subjects of childbearing potential and male subjects with partners of childbearing potential who use effective medical contraception during the study treatment period and for 6 months after the end of dosing; Subjects who voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol- specified visits and relevant procedures. Exclusion Criteria: For NSCLC, histologically or cytologically confirmed the presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components; Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active brain metastases. Other malignancies within 3 years prior to the first dose; Presence of any cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors: Uncontrolled systemic disease as judged by the investigator: History of (noninfectious) interstitial pneumonia (ILD)/noninfectious pneumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis, or suspected ILD/noninfectious pneumonitis at screening that cannot be excluded by imaging; Clinically serious lung injuries caused by lung diseases, including but not limited to any underlying lung diseases or prior pneumonectomy; Presence of active chronic inflammatory bowel disease, GI tract obstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, or acute GI tract bleed; Toxicities treated by prior anti-tumor therapy having not recovered to ≤ Grade 1 (as per NCI CTCAE V5.0) or to the levels specified in the eligibility criteria; Presence of active hepatitis B or hepatitis C; Subjects with HIV test positive or history of AIDS; known active syphilis infection; Known allergy to the study drug or any of its components, and a history of known severe hypersensitivity to other monoclonal antibodies; Prior TROP2-targeted therapy; Prior treatment with any drug therapy targeting topoisomerase I inhibitor, including antibody-drug conjugates (ADCs); Major surgery within 4 weeks prior to the first dose or expected to require major surgery during the study; Systemic anti-infective therapy within 2 weeks prior to the first dose; Receipt of any systemic anti-tumor therapy such as macromolecular targeted therapy, immunotherapy, etc. within 4 weeks prior to the first dose; receipt of small molecule TKIs, nonspecific immunomodulatory therapy , and Chinese patent drug preparations for approved anti-tumor indications within 2 weeks prior to the first dose; Ongoing long-term systemic corticosteroid therapy of > 10 mg prednisone or equivalent dose of systemic corticosteroids or equivalent anti-inflammatory active medication or any form of immunosuppressive therapy prior to the first dose; Live vaccines inoculated within 30 days prior to the first dose or planned to be inoculated during the study; Rapid deterioration of disease, such as significant changes in performance status during the screening process prior to the first dose; Pregnant or lactating women; Presence of local or systemic diseases caused by non-malignancies; or diseases or symptoms secondary to tumors that can lead to high medical risks and/or uncertainties in survival evaluation; Any condition that, in the opinion of the investigator, make the subject unsuitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SKB264 (Cohort 1)<br>SKB264 will be administered as an intravenous (IV) infusion on Day 1 and Day 15 of each 28-day cycle | Drug: SKB264<br>* Subjects of Cohot 1-5 and Part II Test group will receive SKB264 monotherapy<br>|
| Experimental: SKB264 (Cohort 2)<br>SKB264 will be administered as an intravenous (IV) infusion on Day 1 and Day 15 of each 28-day cycle | Drug: SKB264<br>* Subjects of Cohot 1-5 and Part II Test group will receive SKB264 monotherapy<br>|
| Experimental: SKB264 (Cohort 3)<br>SKB264 will be administered as an intravenous (IV) infusion on Day 1 and Day 15 of each 28-day cycle | Drug: SKB264<br>* Subjects of Cohot 1-5 and Part II Test group will receive SKB264 monotherapy<br>|
| Experimental: SKB264 (Cohort 4)<br>SKB264 will be administered as an intravenous (IV) infusion on Day 1 and Day 15 of each 28-day cycle | Drug: SKB264<br>* Subjects of Cohot 1-5 and Part II Test group will receive SKB264 monotherapy<br>|
| Experimental: SKB264 (Cohort 5)<br>SKB264 will be administered as an intravenous (IV) infusion on Day 1 and Day 15 of each 28-day cycle | Drug: SKB264<br>* Subjects of Cohot 1-5 and Part II Test group will receive SKB264 monotherapy<br>|
| Experimental: Part II Test group<br>SKB264 will be administered as an intravenous (IV) infusion on Day 1 and Day 15 of each 28-day cycle | Drug: SKB264<br>* Subjects of Cohot 1-5 and Part II Test group will receive SKB264 monotherapy<br>|
| Active Comparator: Part II Control group<br>Docetaxel will be administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle | Drug: Docetaxel<br>* Part II Control group will receive docetaxel monotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR) as the best overall response assessed per RECIST 1.1. | From baseline until disease progression, death, or other protocol defined reason, up to approximately 21 months. | 
| Incidence and severity of adverse events (AEs) | Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | From subject sign the informed consent form (ICF) to 30 days after the last dose of study treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS is defined as the time from the first dose to progressive disease (PD) or death, whichever occurs first. PD will be assessed per RECIST 1.1. | From baseline until disease progression, death, or other protocol defined reason,up to approximately 21 months. | 
| Duration of response (DOR) | DOR is defined as the time from the date of first documented CR or PR to PD or death due to any cause, whichever occurs first. | From baseline until disease progression, death, or other protocol defined reason, up to approximately 21 months. | 
| Disease control rate (DCR) | DCR is defined as the proportion of subjects with CR, PR or stable disease (SD) as the best overall response assessed per RECIST 1.1. | From baseline until disease progression, death, or other protocol defined reason, up to approximately 21 months. | 
| Overall survival (OS) | OS is defined as the time period from the start of administration to death due to any cause. | From baseline until death due to any cause. | 
| Immunogenicity | Presence of Anti-drug antibodys (ADAs) for SKB264. | From baseline up to 12 months after last patient enrollment. | 
| PK | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB264-ADC, SKB264-TAB and free KL610023. | From baseline up to 12 months after last patient enrollment. | 
| PK | Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB264-ADC, SKB264-TAB and free KL610023. | From baseline up to 12 months after last patient enrollment. |