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.
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.
Aged ≥ 18 years, male or female.
Patients with initial diagnosis of EGFR-mutated NSCLC and histologically or cytologically confirmed transformation to SCLC following treatment with EGFR tyrosine kinase inhibitor.
Progression after only receiving platinum-based treatment regimens.
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.
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.
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.