SKB264 Combinatiton Therapy in Patients With Advanced or Metastatic Non-small Cell Lung Cancer.

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and preliminary antitumor activity of SKB264 in combination with KL-A167 with or without chemotherapy with advanced or metastatic non-small cell lung cancer. The study is divided into two parts. Part 1 will be the safety run-in phase, and Part 2 will be the cohort expansion phase.

Official Title
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A Phase Ⅱ Clinical Study of Combination Therapy of SKB264 in Patients With Advanced or Metastatic Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: SKB264
* Drug: KL-A167
* Drug: Carboplatin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form; Histologically and cytologically confirmed NSCLC; Cohort 1: Patients with locally advanced/metastatic NSCLC with wild-type EGFR and negative ALK fusion gene, no or at most one prior line of systemic chemotherapy regimen for advanced or metastatic NSCLC. Cohort 2: Patients with locally advanced/metastatic NSCLC with wild-type EGFR and negative ALK fusion gene, no prior systemic therapy. Cohort 3: Patients with locally advanced/metastatic NSCLC with EGFR activating mutation and negative ALK fusion gene, who have failed previous treatment with EGFR-TKIs. Provide fresh or archival tumor tissue for biomarker testing and analysis; Patients with at least one measurable lesion per RECIST v1.1 criteria, and patients with only skin or bone lesions cannot be enrolled; Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with an expected survival of ≥ 12 weeks; Adequate organ and bone marrow function For female patients of childbearing age and male patients with partners of childbearing age, they must use effective medical contraception during the study treatment period and for 6 months after the last dose of study medication (see Annex for specific contraceptive measures); Each patient must voluntarily agree to participate in the study, sign the informed consent form, and comply with the protocol-specified visits and relevant procedures. Exclusion Criteria: Presence of small cell lung carcinoma (SCLC) components in histological pathology; History of other malignancies; Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression; Presence of active central nervous system (CNS) metastases; Imaging (CT or MRI) shows that the tumor surrounds important blood vessels, or the investigator determines that the tumor is most likely to invade important blood vessels during the subsequent study to cause fatal major hemorrhage; Serious or uncontrolled cardiac disease or clinical symptoms requiring treatment, including any of the following: Patients with (noninfectious) interstitial lung disease (ILD) or history of pneumonia requiring steroid therapy; patients with serious pulmonary function impairment due to lung disease; Uncontrolled systemic disease as judged by the investigator, included uncontrolled hypertension, uncontrolled diabetes, pesence of pleural effusion, pericardial effusion, or ascites that is clinically symptomatic or requires repeated drainage; Certain viral infections including active hepatitis B or hepatitis C; known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS); or positive syphilis antibody test; Known active tuberculosis; Known hypersensitivity to the study drug or any of its components, or severe allergic reactions to other monoclonal antibodies; Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. Pregnant or lactating women; Any patient whose condition deteriorates rapidly during the screening process prior to the first dose, such as severe changes in performance status, unstable pain requiring adjustment of analgesic therapy, etc Other circumstances that, in the opinion of the investigator, are not appropriate 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+KL-A167<br>Participants received SKB264 followed by KL-A167 | Drug: SKB264<br>* SKB264 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (5mg/kg)<br>Drug: KL-A167<br>* KL-A167 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (1200mg Q3W)<br>|
| Experimental: SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR wide type)<br>Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin | Drug: SKB264<br>* SKB264 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (5mg/kg)<br>Drug: KL-A167<br>* KL-A167 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (1200mg Q3W)<br>Drug: Carboplatin<br>* Carboplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle（AUC 5)<br>Drug: Cisplatin<br>* Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (75mg/m²)<br>|
| Experimental: SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR mutation)<br>Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin | Drug: SKB264<br>* SKB264 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (5mg/kg)<br>Drug: KL-A167<br>* KL-A167 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (1200mg Q3W)<br>Drug: Carboplatin<br>* Carboplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle（AUC 5)<br>Drug: Cisplatin<br>* Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (75mg/m²)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 baseline up to 30 days after last dose or to the beginning of the new anti-cancer therapy, up to 24 months | 
| Objective Response Rate (ORR) | Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. | From baseline to first documented objective response, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival (PFS) was defined as the time from baseline to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions. | From baseline to the first documented disease progression or date of death (whichever occurs first), up to 24 months | 
| Duration of response (DOR) | Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only. | From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 24 months | 
| Disease control rate (DCR) | Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. | From baseline to date of first documented objective response (CR, PR, and SD), up to 24 months | 
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB264-ADC, SKB264-TAB and free KL610023 |  | Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months | 
| Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB264-ADC, SKB264-TAB and free KL610023 |  | Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months | 
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of KL-A167 |  | Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months | 
| Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of KL-A167 |  | Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months | 
| Anti-drug Antibodies (ADA) for SKB264 and KL-A167 |  | Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months |