1989MO - Lurbinectedin (LUR) in combination with pembrolizumab (PBL) in relapsed small cell lung cancer (SCLC): The phase I/II LUPER study

Background

Previously, we established the recommended phase 2 dose (RP2D) of LUR + PBL in the phase 1 stage of this study (J Clin Oncol. 2022;40(suppl 16):8581). Here we present the results on the efficacy and safety of the RP2D.

Methods

LUPER (NCT04358237) is a prospective, open-label, uncontrolled, multicenter, phase 1/2 study of LUR in combination with PBL in patients (pts) with relapsed SCLC. Eligible pts were ≥18 years old, with histologically confirmed SCLC, progression after 1L platinum-based chemotherapy, no prior exposure to immunotherapy, ECOG PS of 0-1, and measurable disease as per RECIST 1.1. Pts with treated, asymptomatic, stable brain metastases (BM) were also included. Treatment consisted of LUR dosed at 3.2 mg/m² IV Q3W in combination with PBL 200 mg IV Q3W until disease progression (PD), unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed overall response rate (ORR) according to RECIST 1.1. Secondary endpoints included investigator-assessed Duration of Response (DoR), Progression-Free Survival (PFS), Overall Survival (OS), and safety as per CTCAE 5.0.

Results

A total of 28 pts were included in the study. Median age was 65 years (range 41-78), 46.4% were female, 64.3% had ECOG PS of 1, 51.9% had platinum-free interval < 90 days, 39.3% had LDH > upper normal limit, and 21.4% had BM. At data cutoff (March 31, 2023),11 (39.3%) pts were still on treatment. The median follow-up was 5.7 months (range: 1.0-25.2). Preliminary ORR was 46.4% (95% CI: 29.5–64.2; p<0.001): 2 confirmed CR, 11 PR (9 confirmed) and 4 SD ≥12 weeks. Median DoR was 11.4 months (range: 0-21.2 months), and 2 (7.1%) pts had durable responses > 12 months. Median PFS was 5.3 months (95% CI: 2.7-12.0). Median OS was 11.1 months (95% CI: 6.9-NR). PBL and LUR discontinuation occurred in 3 (10.7%) and 0 pts due to immune-related AE, respectively. The most common grade 3 and 4 treatment-emergent AEs (>20%) were fatigue, neutropenia, nausea and anemia.

Conclusions

The LUPER study met its primary endpoint. The combination of LUR + PBL is effective in second-line treatment of SCLC with a manageable safety profile. Further research is warranted to confirm the potential of this combination in SCLC patients.

Clinical trial identification

NCT04358237.

Editorial acknowledgement

Legal entity responsible for the study

MEDSIR - Medica Scientia Innovation Research.

Funding

PHARMAMAR (provided financial support and lurbinectedin) and MSD (provided pembrolizumab).

Disclosure

A. Calles Blanco: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Lilly, Merck Sharp & Dohme, Novartis, BMS, Takeda, Sanofi, Janssen; Financial Interests, Personal, Other, Speaker honoraria: Bayer; Financial Interests, Institutional, Research Grant, Drug-only for Investigator-initiated trial.: Merck Sharp & Dohme. 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; Non-Financial Interests, Principal Investigator: BMS, PharmaMar, MSD, Amgen, Novartis, Debiopharm, Daiichi Sankyo, Roche, AstraZeneca. M.J. De Miguel Luken: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, AbbVie, Achilles, Amunix, Arcus, Furmo, Biontech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. R.M. Alvarez: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Roche; Financial Interests, Personal, Other, conference registration: MSD Oncology; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Personal and Institutional, Coordinating PI: Janssen Oncology, Rain Therapeutics, Boehringer Ingelheim, Cebiotex, Novartis. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer BeiGene BioInvent International AB, BMS, Boehringer Ingelheim, Boheringer, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, PharmaMar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith.: Multiple. M. Arregui Valles: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Travel grants: PharmaMar; Financial Interests, Personal and Institutional, Coordinating PI: Lilly. D. Alcalá, M. Fernández, J. Rodríguez Morató: Financial Interests, Personal, Full or part-time Employment: MEDSIR. E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai, Elevation Oncology, Ellipses Pharmacy, SyneosHealth, Genmab, Diaccurate; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, Advisory Role: PsiOxus; Non-Financial Interests, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. R. Palmero Sanchez: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: Guardant Health, Pfizer. M. Jové: Financial Interests, Personal, Invited Speaker, Educational: AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker, Educational activity: BMS; Other, Other, Travel, accommodation and expenses: Takeda, Roche, MSD, VCN. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, BMS, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, BMS International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. All other authors have declared no conflicts of interest.