A Study of SKB264 (MK-2870; Sac-TMT) for the Treatment of Participants With Advanced or Metastatic Non-small Cell Lung Cancer (SKB264-II-04) (MK-2870-003)

Klus Pharma

Status and phase: Enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: SKB264; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Osimertinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05816252

SKB264-II-04

MK-2870-003 (Other Identifier)

2023-507270-41-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability and objective response rate of SKB264 as combination with therapy in subjects with advanced or metastatic non-small cell lung cancer.

Full description

This is a multicenter, open-label study of SKB264 as combination therapy or monotherapy in subjects with NSCLC. Approximately 498 subjects will be enrolled in this study including around 88 subjects for the safety run-in period and 410 subjects for the expansion period.

Enrollment: 498 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Subjects must be at least 18 years of age on day of signing informed consent, regardless of gender;
2. Subjects with histologically or cytologically confirmed locally advanced or metastatic NSCLC ;
3. Subjects for NSCLC should be confirmed to be EGFR (Epidermal growth factor receptor) wild-type and ALK (Anaplastic lymphoma kinase) fusion gene negative; or confirmed to harbor EGFR mutation;
4. Locally advanced or metastatic NSCLC subjects without actionable EGFR mutations and ALK fusion genes, no prior systemic treatment; subjects with EGFR mutation, no prior systemic treatment or failed prior EGFR-TKI (Tyrosine kinase inhibitor) treatment;
5. Subjects are able to provide tumor blocks or slides before the first dose of study intervention;
6. Subject must have at least one radiographically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria;
7. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1;
8. Life expectancy at least 3 months for the subject;
9. Adequate organ function;
10. Subjects must have recovered from all toxicities led by prior treatment;
11. Contraceptive methods used by male and female subjects must comply with contraceptive methods of local regulations for clinical study subjects;
12. Subjects should voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures.

Exclusion Criteria

1. Subjects with mixed SCLC histopathological features;
2. Subjects with a known history of prior malignancy;
3. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases;
4. Subjects with ≥ Grade 2 peripheral neuropathy;
5. Subjects who had arteriovenous thromboembolic events, tumor invasion/encasement of vital organs/vessels, risk of esophageal-tracheal/pleural fistula, or current superior vena cava syndrome;
6. Subjects with active inflammatory bowel disease or previous clear history of inflammatory bowel disease;
7. Subjects who suffer from cardiovascular diseases of clinical significance;
8. Subjects with a history of interstitial lung disease (ILD)/non-infectious pneumonitis that required steroids;
9. Subjects with uncontrolled systemic disease as judged by the Investigator;
10. Subjects with active autoimmune disease that required systemic treatment in the past 2 years;
11. Subjects with active hepatitis B or hepatitis C;
12. Subjects with known history of Human Immunodeficiency Virus (HIV)
13. Subjects with known active tuberculosis;
14. Subjects with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study;
16. Subjects whose condition deteriorated rapidly, such as severe changes in performance status, during the screening process prior to the first dose of study intervention;
17. Subjects with other circumstances that, in the opinion of the Investigator, are not appropriate for participation in this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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498 participants in 8 patient groups

Cohort 1 1L NSCLC, EGFR/ALK negative and PD-L1 TPS ≥ 1%

Experimental group

Description:

SKB264 (Dose Level 1) + Pembrolizumab

Treatment:

Drug: Pembrolizumab

Drug: SKB264

Cohort 3 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level

Experimental group

Description:

SKB264 (Dose Level 1') + Pembrolizumab + Carboplatin

Treatment:

Drug: Pembrolizumab

Drug: Carboplatin

Drug: SKB264

Cohort 4 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level

Experimental group

Description:

SKB264 (Dose Level 1'') + Pembrolizumab + Carboplatin

Treatment:

Drug: Pembrolizumab

Drug: Carboplatin

Drug: SKB264

Cohort 5 NSCLC with EGFR mutation and after failure of EGFR TKI therapy

Experimental group

Description:

SKB264 (Dose Level 1') + Carboplatin

Treatment:

Drug: Carboplatin

Drug: SKB264

Cohort 6 NSCLC with EGFR mutation and after failure of EGFR TKI therapy

Experimental group

Description:

SKB264 (Dose Level 1'') + Carboplatin

Treatment:

Drug: Carboplatin

Drug: SKB264

Cohort 7 1L NSCLC with EGFR mutation

Experimental group

Description:

SKB264 (Dose Level 1) + Osimertinib

Treatment:

Drug: Osimertinib

Drug: SKB264

Cohort 7-1 1L NSCLC with EGFR mutation

Experimental group

Description:

SKB264 (Dose Level 2) + Osimertinib

Treatment:

Drug: Osimertinib

Drug: SKB264

Cohort 9 2/3L NSCLC EGFR/ALK negative

Experimental group

Description:

SKB264 (Dose Level 1)

Treatment:

Drug: SKB264