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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
BL0020 will be administered via intravenous infusion on Day 1 of each 21-day treatment cycle.
Shanghai Chest Hospital
Shanghai, China
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
Time frame: Throughout the study for approximately 2 years
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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).
Time frame: Throughout the study for approximately 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.