A Clinical Study for the Efficacy and Safety of BL0020 Injection in Patients With Small Cell Lung Cancer Transformed From Non-Small Cell Lung Cancer Following EGFR TKI Therapy

An Open-Label, Single-Arm Phase I/II Clinical Study to Evaluate the Efficacy and Safety of BL0020 Injection in Patients With Small Cell Lung Cancer Transformed From Non-Small Cell Lung Cancer Following EGFR TKI Therapy

The primary treatment option for non-small cell lung cancer (NSCLC) adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutation is EGFR tyrosine kinase inhibitor (TKI). After a certain period of treatment with EGFR TKI, acquired resistance emerges most frequently with a secondary mutation, p.T790M, followed by MET amplification. Interestingly, up to 3-14% of patients experience histological transformation into small cell lung cancer (SCLC), which has an aggressive clinical course and a poor prognosis.

The transformed SCLC retains the original EGFR mutation but significantly down regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. However, little is known about the clinical outcomes of transformed SCLC, with limited studies arguing that their outcomes are similar to those of de novo SCLC, where the median overall survival is approximately 9 to 10 months after the transformation.

At present, there is no standard treatment regimen for patients with SCLC transformed from NSCLC following EGFR TKI therapy.

BL0020 is a polymer-drug conjugate consisting of Topoisomerase I inhibitor SN-38 (7-ethyl-10-hydroxycamptothecin) conjugated by a peptide linker to a PEG-modified poly(ε-L-lysine) polymer. In the ongoing first-in-human study of BL0020, significant efficacy has been observed with BL0020 monotherapy in SCLC patients who have relapsed or progressed following at least first-line platinum-based systemic treatment.

Based on previous clinical and preclinical outcomes that show similar disease characteristics between SCLC transformed from NSCLC following EGFR TKI therapy and de novo SCLC, this study is designed to evaluate the clinical efficacy and safety of BL0020 in patients with transformed SCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Carcinoma of Lung
• Intervention / Treatment: Drug: BL0020

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhuolun Fang; Phone Number: +86 18357916536; Email: fangzhuolun@bestlinkbio.com

Study Locations

• China
  • Shanghai, China, 200030
    • Shanghai Chest Hospital
    • Principal Investigator: Shun Lu
    • Contact: Shun Lu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 initial diagnosis of EGFR-mutated NSCLC and histologically or cytologically confirmed transformation to SCLC following treatment with EGFR tyrosine kinase inhibitor.

4. After transformation to SCLC, the patient's prior treatment history must meet one of the following criteria:

   • Progression after only receiving platinum-based treatment regimens.
   • No prior systemic therapy for SCLC.
5. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 at screening.
6. Life expectancy ≥ 12 weeks.

Exclusion Criteria:

1. Patients with symptomatic brain metastases or carcinoma meningitis. Note:

   • Patients with treated brain metastases may participate in this study if the patient has completed radiotherapy or surgery for brain metastases ≥ 4 weeks prior to study entry, and neurologically stable ≥ 4 weeks after radiotherapy or surgery treatment [i.e., no new findings on brain imaging and no new neurologic deficits from brain metastasis on screening examination, and high doses of corticosteroids (> 10 mg prednisone daily or equivalent) were not required within 4 weeks prior to enrollment].
   • Patients with brainstem metastases or spinal cord compression (detected by radiographic imaging, even if they did not have symptoms) were not eligible.
2. 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.
3. Patients with tumors that had invaded important blood vessels as shown in the screening imaging and that the investigators assessed were highly likely to cause fatal bleeding during the study.
4. Patients whose pericardial effusion, pleural effusion or ascites remain uncontrollable after intervention.
5. Patients with Gilbert's syndrome disease.
6. Patients who have a known diagnosis of Human Immunodeficiency Virus (HIV) infection or HIV antibody test positive during screening.
7. Patients with active hepatitis C or chronic hepatitis B at screening ("active hepatitis" defined as HCV RNA level ≥ 200 IU/mL for hepatitis C or HBV DNA level ≥ 2000 IU/mL for hepatitis B at screening). In addition, eligible hepatitis B or hepatitis C patients must agree to antiviral treatment according to the treatment guidelines.
8. Patients who have not sufficient baseline organ function.
9. Those who are known to be allergic to the active ingredient or excipients of the investigational product BL0020 Injection, or who have a predisposition to allergy.
10. Patients who are taking anticoagulant therapy (prophylactic use of low-dose aspirin [≤ 100 mg/day] or low molecular weight heparin is allowed).
11. Those who have received live or attenuated vaccines (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, BCG, typhoid vaccine, etc.) within 4 weeks before enrollment or scheduled to receive during the study.
12. Pregnant or lactating women.
13. Patients who are assessed disqualified to join clinical studies by investigator due to any causes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BL0020	Drug: BL0020; BL0020 will be administered via intravenous infusion on Day 1 of each 21-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the proportion of patients with the best responses of Complete Response (CR) and Partial Response (PR) observed after study treatment	Throughout the study for approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR is defined as the time from the initial response (complete response [CR] or partial response [PR]) until first objective radiographic tumor progression or death from any cause	Throughout the study for approximately 2 years
Disease control rate (DCR)	DCR is the sum of complete response (CR), partial response (PR), and stable disease (SD) rates	Throughout the study for approximately 2 years
Progression-free survival (PFS)	PFS is defined as the time from the start date of study treatment until first objective radiographic tumor progression or death from any cause	Throughout the study for approximately 2 years
Overall survival (OS)	OS is defined as the time from the start date of study treatment until death from any cause	Throughout the study for approximately 2 years
3-Month Progression-Free Survival (PFS3)	PFS3 is defined the proportion of patients who have not experienced first objective radiographic tumor progression or death due to any cause after 3 months from the start date of the study treatment	From the first study treatment to the 3-month time point
6-Month Progression-Free Survival (PFS6)	PFS6 is defined the proportion of patients who have not experienced first objective radiographic tumor progression or death due to any cause after 6 months from the start date of the study treatment	From the first study treatment to the 6-month time point
9-Month Progression-Free Survival (PFS9)	PFS9 is defined the proportion of patients who have not experienced first objective radiographic tumor progression or death due to any cause after 9 months from the start date of the study treatment	From the first study treatment to the 9-month time point
12-Month Progression-Free Survival (PFS12)	PFS12 is defined the proportion of patients who have not experienced first objective radiographic tumor progression or death due to any cause after 12 months from the start date of the study treatment	From the first study treatment to the 12-month time point
6-Month Overall Survival rate (OS6)	OS6 is defined the proportion of patients who are alive 6 months from the start date of the study treatment.	From the first study treatment to the 6-month time point
12-Month Overall Survival rate (OS12)	OS12 is defined the proportion of patients who are alive 12 months from the start date of the study treatment	From the first study treatment to the 12-month time point
Incidence of Treatment-Emergent Adverse Events (TEAEs)	TEAEs are defined as those Adverse Events (AEs) with start or worsening date during the on-treatment period (from the first dose date of study treatment to 30 days after the last dose date of study treatment).	Throughout the study for approximately 2 years

Collaborators and Investigators

• Sponsor: Shanghai Best-Link Bioscience, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): March 27, 2026
• Primary Completion (Estimated): December 22, 2027
• Study Completion (Estimated): February 20, 2028

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 14, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: BL0020-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No