A Clinical Study for the Safety and Efficacy of BL0020 Injection in Combination With Toripalimab Injection in Patients With Recurrent Extensive-Stage Small Cell Lung Cancer

An Open, Multi-center Phase I Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of BL0020 Injection in Combination With Toripalimab Injection in Patients With Recurrent Extensive-Stage Small Cell Lung Cancer

Lung cancer remains the leading cause of cancer deaths worldwide; in 2022, there were approximately 2.48 million new cases and 1.8 million deaths from lung cancer globally. Globally, lung cancer is the leading cause of cancer-related deaths in men and the second leading cause in women after breast cancer. Among them, small cell lung cancer (SCLC) accounts for approximately 14% of all newly diagnosed lung cancers. Small cell lung cancer (SCLC) is a highly heterogeneous and aggressive disease with poor survival outcomes.

A 2-stage system dividing patients into limited and extensive disease was developed in 1973 by the United States (US) Veteran's Administration Lung Cancer Study Group (VALG), which has been used to this day. Patients with limited-stage SCLC can be treated with chemotherapy and radiation with the potential for long-term survival. However, the majority (approximately 70%) of patients with SCLC are diagnosed with extensive-stage SCLC (ES-SCLC), which has poor survival prospects. Chest pain, dyspnea, and cough are among the most frequent disease-related symptoms experienced by patients with SCLC. Immune checkpoint inhibitors in combination with platinum-based systemic therapy can palliate symptoms and prolong survival for patients with ES-SCLC. However, long-term survival is rare.

The current standard first-line treatment for patients with ES-SCLC is immune checkpoint inhibitors in combination with platinum-based systemic therapy. Despite the impressive high objective response rates (approximately 60%-80%) observed with first-line treatment regimens, the median overall survival (OS) of patients rarely exceeds 16 months, and the median progression-free survival (PFS) is also limited to around 5 months. Second-line and subsequent therapeutic options are limited. The main treatment drugs include Topotecan, Lurbinectedin, Tarlatamab, etc., with objective response rates rarely exceeding 40%. Therefore, there is a significant need for improved novel treatment options for patients with ES-SCLC.

This is a multi-center, open-label study. The study is designed to evaluate the safety, tolerability, and preliminary efficacy of Toripalimab in combination with BL0020 in patients with ES-SCLC who have relapsed or progressed following first-line platinum-based systemic treatment regimen.

Inclusion Criteria:

1. Volunteer to participate in the study, be able to understand the requirements of a clinical study, and willingness to sign a written informed consent form.
2. Aged ≥ 18 years, male or female.
3. Patients with histologically or cytologically confirmed ES-SCLC (per the American Veterans Administration Lung Study Group [VALG] staging system) who have relapsed or progressed following first-line platinum-based systemic treatment regimen.
4. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 at screening.
5. Life expectancy ≥ 12 weeks.

Exclusion Criteria:

1. Chemotherapy-free interval (CTFI: time from the last dose of first-line platinum-based chemotherapy to disease progression) < 30 days, regardless of maintenance treatment with immune checkpoint inhibitors.
2. Histologically or cytologically confirmed combined SCLC and transformed SCLC.
3. Patients with central nervous system (CNS) metastases or carcinoma meningitis. Note: Patients with asymptomatic CNS metastases may participate in this study if they meet all the following criteria:

1)Patients with treated CNS metastases may participate in this study if the patient has completed radiotherapy or surgery for CNS metastases ≥ 4 weeks prior to study entry, and if the patient is neurologically stable ≥ 4 weeks after radiotherapy or surgery treatment (no new neurologic deficits from brain metastasis on screening clinical examination, no new findings on CNS imaging, and high doses of corticosteroids [> 10 mg prednisone daily or equivalent] were not required within 4 weeks prior to screening).

2)Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord).

4.Previous or current autoimmune disease, including but not limited to Crohn's disease, ulcerative colitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the following allowed exceptions:

1. Patients with a history of autoimmune-related hypothyroidism on thyroid replacement hormone therapy.
2. Patients with controlled Type I diabetes mellitus on an insulin regimen.
3. Patients with vitiligo. 5.Patients with Gilbert's syndrome disease. 6.Patients who have a history of another primary malignancy (with the exception of patients with cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of uterine cervix). A patient who has had no evidence of disease from another primary cancer for 3 or more years is allowed to participate in the study.

7.Poorly controlled hypertension (defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg), or a history of hypertensive crisis or hypertensive encephalopathy.

8.Patients who have a known diagnosis of Human Immunodeficiency Virus (HIV) infection or HIV antibody test positive during screening.

9.Active hepatitis C or chronic hepatitis B at screening ("active hepatitis" defined as HCV RNA ≥ ULN at the local clinical site for hepatitis C, or HBV DNA ≥ ULN at the local clinical site for hepatitis B). Note: Antiviral therapy may be administered during the study to prevent viral reactivation if necessary.

10.Patients who have not sufficient baseline organ function. 11.Those who have received live or attenuated vaccines (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, BCG, typhoid vaccine) within 4 weeks before enrollment or scheduled to receive during the study.

12.Known allergy to Toripalimab, BL0020, or any of their excipients. 13.Pregnant or lactating women. 14.Patients who are assessed disqualified to join clinical studies by investigator due to any causes.