Abstract 199P
Background
Metastatic triple-negative breast cancer (mTNBC) carries a poor prognosis with rapid progression and lower survival rates compared to other breast cancer types. To address this, TILS001 trial (NCT05451784) evaluates the safety, tolerability, and effectiveness of infused PD1+ T cells (NUMARZU-001). TILS001 is a single-arm, multicenter phase I/II study evaluating NUMARZU-001 as a treatment for advanced or mTNBC. The results of the safety run-in phase are outlined below.
Methods
The study consists of three sequential phases before TILs infusion. In the molecular prescreening phase, tumor samples are evaluated for PD1 mRNA expression. In the prescreening phase, patients with less than 5 prior treatments and at least 1 accessible target lesion whose tumors have high PD1 mRNA levels based on a predetermined cutoff, are eligible for TILs generation. Finally, after achieving full expansion of PD1+ TILs, patients undergo a non-myeloablative lymphodepleting chemotherapy regimen, followed by NUMARZU-001 infusion and IL-2 treatment.
Results
At data cut-off (September 2023), molecular prescreening was conducted on tumor samples from 51 patients, with 18 undergoing prescreening. From these, 3 received treatment with NUMARZU-001. The median age was 49 years. One patient had received 4 prior treatment lines, while the other two had received 2 lines. Among the reported grade (G) 3 and 4 adverse events, most were related to blood system disorders secondary to chemotherapy (including anemia, neutropenia, and lymphocyte count decrease). Other side effects included analytical abnormalities (increased GGT G2, hyponatremia G2, hypomagnesemia G1, increased AST or ALT G1), anorexia G2, and nervous system and psychiatric disorders G1. No serious adverse events (SAE) were reported. One patient had a partial response, and another showed stable disease as the best response to treatment.
Conclusions
NUMARZU-001 has shown a manageable safety profile in the safety run-in phase. The independent safety data monitoring committee recommended continuing recruitment to expand the pool of treated patients and evaluate its efficacy further.
Clinical trial identification
EudraCT 2020-003638-19; NCT05451784.
Legal entity responsible for the study
Fundació Clínic per a la Recerca Biomèdica.
Funding
Asociación Española Contra el Cáncer (AECC).
Disclosure
M. Santisteban Eslava: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal and Institutional, Research Grant: GENENTECH; Non-Financial Interests, Member: GEICAM, SOLTI, BIG. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Farma, Sanofi Avenits, Seagen, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim, Bristol Meyers Squibb, Genentech, Innoup, Millenium; Financial Interests, Personal, Other, SC: Byondis B.V., GSK, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. L. Alvarez-Vallina: Financial Interests, Personal, Invited Speaker: Amgen, GSK, MSD, Merck KGaA; Financial Interests, Institutional, Invited Speaker: Miltenyi Biotec; Financial Interests, Personal, Other, Chair of Immunology, Universidad Francisco de Vitoria: Merck KGaA; Financial Interests, Personal, Advisory Board: Leadartis; Financial Interests, Personal, Stocks/Shares: Leadartis, STAb Therapeutics; Non-Financial Interests, Principal Investigator: AECC, CRIS Cáncer Foundation, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Fundacion La Caixa. J.J. Lasarte: Financial Interests, Personal, Invited Speaker: Celgene (BMS), Novartis; Financial Interests, Personal, Expert Testimony: Tyris therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca. A. Gros: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Singula Bio, BioNTech; Financial Interests, Personal, Other, Consulting: Instil Bio; Financial Interests, Personal, Expert Testimony: Pact Pharma, Inc.; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Consultant: Genentech; Financial Interests, Personal, Royalties: Intima Bioscience, Inc., Intelia Therapeutics, Inc., Tailored Therapeutics, LLC, Cellular Biomedicine Group, Inc., Geneius Biotechnology, Inc.; Financial Interests, Institutional, Research Grant: Novartis, Roche, Merck KGaA; Financial Interests, Institutional, Other, Project in collaboration: RootPath; Non-Financial Interests, Member: American Association for Cancer Research, SITC, EACR. Á.M. Vizcay: Financial Interests, Personal, Invited Speaker, CDK4/6 inhibitors-related toxicity: Pfizer; Financial Interests, Personal, Invited Speaker, Role of PD-L1 in solid tumors: BMS. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Lilly, MSD, Relay Therapeutics, Roche, Seagen, Cureo Science, iOne, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Pfizer, Roche, Seagen, AstraZeneca, Lilly, Medscape, AstraZeneca, AstraZeneca; Financial Interests, Personal, Other, Educational activity: Libbs; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals, Pfizer; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Member of Board of Directors, Head: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. P. Tolosa Ortega: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Lilly, Seagen, AstraZeneca, Daiichi Sankyo and MSD; Financial Interests, Personal, Advisory Board: Novartis, Adamed, Seagen and Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment, Medical Advisor and Madical Monitor: SOLTI; Financial Interests, Institutional, Funding: Novartis. F. Brasó-Maristany: Financial Interests, Personal, Full or part-time Employment, part time employment: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: EP23382703 and EP23383369: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: PCT/EP2022/086493, PCT/EP2023/060810: Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer. L. Villanueva: Other, Institutional, Proprietary Information, PCT / EP2022 / 054803: Josep Carreras Leukaemia Research Institute. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. A. Prat: Financial Interests, Personal, Invited Speaker: Roche, 1TRIALSP, S.L.; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, Reveal Genomics; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L., ; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Funding: Reveal Genomics; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA; Non-Financial Interests, Personal, Other, Research Foundation that gives grants to researchers: FERO. All other authors have declared no conflicts of interest.