Lurbinectedin (LUR) has received approval in the United States and several other nations for the treatment of adult patients with metastatic small cell lung cancer (SCLC) who have experienced disease progression following platinum-based chemotherapy. Preclinical studies have demonstrated a synergistic effect when LUR is combined with irinotecan (IRI). A phase 1b/2 clinical trial (NCT02611024) involving 101 patients with relapsed SCLC indicated promising efficacy and an acceptable safety profile when administered at the recommended dose of LUR 2.0 mg/m2 on day 1 in conjunction with IRI 75 mg/m2 on days 1 and 8, every 3 weeks, accompanied by primary granulocyte colony-stimulating factor prophylaxis. An analysis of a subset of SCLC patients with a chemotherapy-free interval (CTFI) >30 days was presented at ESMO 2024.
PM1183-A-014-15 is a phase 1/2 trial of the combination of LUR with IRI in pretreated patients with selected advanced solid tumors. The expansion cohort in second-line SCLC patients included 101 patients. Eligibility criteria included confirmed SCLC, progression after 1 platinum-based line, CTFI >30 days, controlled brain metastases, and ECOG performance status ≤1.
Of the 101 evaluable patients with SCLC, 74 exhibited a CTFI >30 days. The baseline characteristics of these patients included a median age of 64 years, 60.8% males, 73.0% with an ECOG performance status of 1, 33.8% presenting with central nervous system involvement, 31.1% having bulky disease, and 40.5% having received prior immunotherapy. Additionally, 33.8% of the patients had a CTFI <90 days. On average, each patient underwent 7 treatment cycles; notably, 27.0% of patients received >10 cycles. In all patients with CTFI >20 days, the overall response rate was 52.7%, the median duration of response was 7.6 months, the median progression-free survival was 5.0 months, the median overall survival (OS) was 12.7 months, and the OS rate at 12 months was 52.0%. Treatment-related adverse events (AEs) were reported in 98.6% of patients. Among these, 73.0% experienced grade ≥3 events, with the most significant occurrences being neutropenia (60.8%), anemia (28.4%), diarrhea (18.9%), fatigue (16.2%), and febrile neutropenia (14.9%). Additionally, 32.4% of patients faced serious treatment-related AEs, and 4.1% opted to discontinue treatment due to these AEs. It is worth noting that there were no treatment-related deaths.
The combination of LUR and IRI demonstrated significant therapeutic potential and a satisfactory safety profile in patients with relapsed SCLC following 1 platinum-based treatment. The efficacy was observed not only in patients with sensitive disease (CTFI >90 days) but also in those with a CTFI of 30 to 90 days, a group generally associated with a poor prognosis. These results support the justification for incorporating this combination into the ongoing LAGOON trial (NCT05153239) for relapsed SCLC patients with a CTFI >30 days.
Source: Zugazagoitia J, Gonzalez AF, Mendivil AFN, et al. Phase II data of lurbinectedin (LUR) and irinotecan (IRI) in relapsed small cell lung cancer (SCLC) patients (pts) with chemotherapy-free interval (CTFI) >30 days (d). Barcelona, Spain, & online: presented at ESMO Congress 2024; abstract 1790P.