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)

BackgroundLUR has been approved in the US and other countries for treating adult pts with metastatic SCLC and disease progression on or after platinum (Pt)-based chemotherapy. LUR with IRI showed synergy in preclinical studies. A phase Ib/II trial (NCT02611024) found promising activity and a manageable safety profile in 101 pts with relapsed SCLC treated at the RD of LUR 2.0 mg/m2 on Day (D)1 + IRI 75 mg/m2 on D1, D8 every three weeks with primary G-CSF prophylaxis. An analysis of a subpopulation of SCLC pts with CTFI>30 d is presented here.MethodsEligibility criteria: confirmed SCLC, progression after one Pt-based line, CTFI>30 d, controlled brain metastases and ECOG PS ≤ 1.Results74 of the 101 evaluable SCLC pts had CTFI>30 d. Baseline characteristics: median age 64 y (range, 45-77 y), 60.8% males, 73.0% ECOG PS 1, 31.1% CNS involvement, 31.1% bulky disease and 40.5% pretreated with immunotherapy. 33.8% had CTFI <90 d. Median CTFI 108.5 d (range, 37-323 d). Median no. of cycles per pt was 7 (range, 1-34); 27.0% received >10 cycles. Efficacy results assessed by independent review committee are shown below: Table: 1790P All pts with CTFI>30 d (n=74) CTFI 30-90 d (n=25) CTFI≥90 d (n=49) ORR, % (95% CI) 51.4 (39.4-63.1) 32.0 (14.9-53.5) 61.2 (46.2-74.8) DoR (mo), median (95% CI) 8.2 (5.4-11.7) 7.6 (3.7-9.7) 8.4 (4.6-12.7) PFS (mo), median (95% CI) 5.6 (4.1-7.2) 4.3 (3.0-7.0) 6.2 (4.2-9.6) OS (mo), median (95% CI) 12.7 (9.1-14.1) 8.8 (3.7-13.6) 14.0 (10.1-16.1) OS rate at 12 mo, % (95% CI) 52.5 (40.1-64.9) 34.1 (13.8-54.5) 61.7 (46.6-76.7) CI, confidence interval; CTFI, chemotherapy-free interval; d, days; DoR, duration of response; mo, months; ORR, overall response rate; OS, overall survival; PFS, progression free survival. Treatment-related adverse events (AEs) occurred in 98.6% of pts. 71.6% had grade ≥3 events; most relevant were neutropenia (59.5%), anaemia (28.4%), diarrhoea (18.9%), fatigue (16.2%), and febrile neutropenia (13.5%). 31.1% of pts had treatment-related serious AEs, and 6.8% discontinued due to treatment-related AEs. No treatment-related deaths occurred.ConclusionsThe LUR+IRI combination had a highly promising activity and an acceptable safety profile in pts with relapsed SCLC after one Pt-based line. Efficacy was evident not only in sensitive disease (CTFI>90 d) but also in pts with CTFI 30-90 d, who typically have a poor prognosis. These findings bolster the rationale for including this combination in the currently recruiting LAGOON trial (NCT05153239) in relapsed SCLC pts with CTFI>30 d.Clinical trial identificationNCT05153239.Legal entity responsible for the studyPharmaMar.FundingHas not received any funding.DisclosureJ. Zugazagoitia: Financial Interests, Personal, Invited Speaker: Takeda, BMS, AstraZeneca, NanoString, Guardant Health; Financial Interests, Personal, Advisory Board: Roche, Sanofi, BMS, Pfizer, Novartis, Janssen; Financial Interests, Personal and Institutional, Funding, Research Grant: AstraZeneca, Roche, BMS. A. Falcon Gonzalez: Financial Interests, Personal, Advisory Board: Seagen, Novartis, Pfizer, AstraZeneca, Roche, Esteve; Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly, Grunenthal pharma, Roche, AstraZeneca, Daiichi Sankyo. A.F. Navarro Mendivil: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Oryzon Genomics, Amgen, Hengenix Biotech, MedSIR, BMS; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Takeda, Tecnofarma; Non-Financial Interests, Principal Investigator: BMS, PharmaMar, MSD, Amgen, Novartis, Debiopharm, Daiichi Sankyo, Roche, AstraZeneca. P.F. Simoes da Rocha: Other, Congress and travel: MSD, BMS, AstraZeneca, Kyowa Kirin. A. Artal: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Roche, Takeda, Pfizer. S. Martínez, J.A. López-Vilariño, C. Kahatt, J. Gómez: Financial Interests, Personal, Member: PharmaMar. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati, Boehringer Ingelheim; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Personal, Other, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group; Non-Financial Interests, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Leadership Role, President: Oncosur Foundation. All other authors have declared no conflicts of interest.