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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05351788
• Other study ID #: SKB264-?-05
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2022
• Est. completion date: April 2026

Study information

• Verified date: December 2023
• Source: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
• Contact: XiaoPin Jin
• Phone: 028-67255165
• Email: jinxp[@]kelun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: April 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Males or females = 18 and = 75 years of age at the time of signing the informed consent form;

2. Histologically and cytologically confirmed NSCLC;

3. 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.

4. Provide fresh or archival tumor tissue for biomarker testing and analysis;

5. Patients with at least one measurable lesion per RECIST v1.1 criteria, and patients with only skin or bone lesions cannot be enrolled;

6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with an expected survival of = 12 weeks;

7. Adequate organ and bone marrow function

8. 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);

9. 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:

1. Presence of small cell lung carcinoma (SCLC) components in histological pathology;

2. History of other malignancies;

3. Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression;

4. Presence of active central nervous system (CNS) metastases;

5. 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;

6. Serious or uncontrolled cardiac disease or clinical symptoms requiring treatment,

including any of the following:

7. Patients with (noninfectious) interstitial lung disease (ILD) or history of pneumonia requiring steroid therapy; patients with serious pulmonary function impairment due to lung disease;

8. 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;

9. 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;

10. Known active tuberculosis;

11. Known hypersensitivity to the study drug or any of its components, or severe allergic reactions to other monoclonal antibodies;

12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.

13. Pregnant or lactating women;

14. 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

15. Other circumstances that, in the opinion of the investigator, are not appropriate for participation in this study.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• SKB264
SKB264 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (5mg/kg)
• KL-A167
KL-A167 will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (1200mg Q3W)
• Carboplatin
Carboplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle(AUC 5)
• Cisplatin
Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle (75mg/m²)

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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