Clinical trial NCT05631262: SKB264 Monotherapy in Selected Subjects with Advanced Solid Tumors
Official title: A Multicenter, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of SKB264 Monotherapy in Selected Subjects with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Selected Subjects with Advanced Solid Tumors
Lead sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-11-30
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Males or females aged ≥ 18 to ≤ 75 years at the time of signing the ICF;
2. 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) ;
3. 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;
4. 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;
5. 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;
6. 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;
7. 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;
8. PD as assessed by imaging on or after the most recent treatment for locally advanced or metastatic disease;
9. Ability to provide fresh or archival tumor tissue for biomarker testing and analysis.
10. At least one measurable target lesion per RECIST 1.1;
11. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
12. Expected survival ≥ 12 weeks;
13. Adequate organ and bone marrow function;
14. 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;
15. 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:

1. For NSCLC, histologically or cytologically confirmed the presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components;
2. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active brain metastases.
3. Other malignancies within 3 years prior to the first dose;
4. Presence of any cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors:
5. Uncontrolled systemic disease as judged by the investigator:
6. 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;
7. Clinically serious lung injuries caused by lung diseases, including but not limited to any underlying lung diseases or prior pneumonectomy;
8. Presence of active chronic inflammatory bowel disease, GI tract obstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, or acute GI tract bleed;
9. 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;
10. Presence of active hepatitis B or hepatitis C;
11. Subjects with HIV test positive or history of AIDS; known active syphilis infection;
12. Known allergy to the study drug or any of its components, and a history of known severe hypersensitivity to other monoclonal antibodies;
13. Prior TROP2-targeted therapy;
14. Prior treatment with any drug therapy targeting topoisomerase I inhibitor, including antibody-drug conjugates (ADCs);
15. Major surgery within 4 weeks prior to the first dose or expected to require major surgery during the study;
16. Systemic anti-infective therapy within 2 weeks prior to the first dose;
17. 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;
18. 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;
19. Live vaccines inoculated within 30 days prior to the first dose or planned to be inoculated during the study;
20. Rapid deterioration of disease, such as significant changes in performance status during the screening process prior to the first dose;
21. Pregnant or lactating women;
22. 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;
23. Any condition that, in the opinion of the investigator, make the subject unsuitable for participation in this study.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 21 months.
measure: Incidence and severity of adverse events (AEs)
timeFrame: From subject sign the informed consent form (ICF) to 30 days after the last dose of study treatment.
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From baseline until disease progression, death, or other protocol defined reason,up to approximately 21 months.
measure: Duration of response (DOR)
timeFrame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 21 months.
measure: Disease control rate (DCR)
timeFrame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 21 months.
measure: Overall survival (OS)
timeFrame: From baseline until death due to any cause.
measure: Immunogenicity
timeFrame: From baseline up to 12 months after last patient enrollment.
measure: PK
timeFrame: From baseline up to 12 months after last patient enrollment.
measure: PK
timeFrame: From baseline up to 12 months after last patient enrollment.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: