Abstract 197P
Background
Within HER2+ ABC, estrogen receptor (ER) negative or PAM50 non-luminal disease (HER2-enriched and Basal-like) are more immunogenic, have higher tumor-infiltrating lymphocytes and higher expression of immune-related genes. Here, we report the interim efficacy and safety data of the ATREZZO trial (NCT04759248).
Methods
ATREZZO is a single-arm, phase II trial evaluating atezolizumab, trastuzumab and vinorelbine combination in patients (pts) with HER2+, ER– or ER+ and PAM50 non-luminal subtypes ABC. Key inclusion criteria include progression to prior trastuzumab and antibody drug conjugate and presence of measurable disease. The primary endpoint was overall response rate (ORR). Tumor samples are mandatory to assess PAM50 and PD-L1 IHC (SP142) status. Based on a Simon’s two stage design, the analysis of the first stage was planned after 19 evaluable pts, if at least 3 pts achieved an objective response, the trial would continue up to recruit 55 evaluable pts for a target ORR ≥ 13. The evaluable population was defined as all pts who had received at least one dose of treatment and had at least one postbaseline tumor assessment.
Results
61 pts were pre-screened, and 42 ER+ and non-luminal or ER- tumors were identified. From these, 23 pts were recruited, and 19 were evaluable for primary endpoint. Baseline pts characteristics: median age 58 years (33-72), ER+ 32% (6/19), visceral disease 90% (17/19), median of 3 (1-4) prior lines for ABC and PD-L1 IHC tumors+ 16% (3/19). At the time of data cut-off (Feb, 2022), 14 pts had stopped their treatment because of PD and 1 due to toxicity. 4 pts were still on treatment. The ORR was 31.6% (6/19, 95% CI 12.59-56.57), meeting the pre-specified ORR for the stage I of the trial. 42.1% of patients (8/19) experienced grade 3-4 AEs.
Conclusions
The stage I of ATREZZO met its pre-specified endpoint. Completion of the stage II part of the trial with the inclusion of up to 55 pts is warranted to assess the activity of this combination in this group of pts. Correlative studies are ongoing and will be presented at the meeting.
Clinical trial identification
EudraCT 2020-000245-13, NCT04759248 First posted: October 6, 2022. Sponsor: SOLTI Cancer Research Group. This study was funded by Roche Farma S.A.
Legal entity responsible for the study
SOLTI.
Funding
Roche Farma S.A.
Disclosure
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, Invited Speaker, 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. 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. S. González-Santiago: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, GSK, Pierre Fabre; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Clovis, Pfizer. S. Escrivá-De-Romaní: Financial Interests, Personal, Other, Consulting Fees: AstraZeneca Daiichi Sankyo, F Hoffmann-La Roche Ltd., Pierre-Fabre, Seagen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca Daiichi Sankyo, F Hoffmann-La Roche Ltd., Pfizer, Pierre-Fabre, Seagen, Novartis; Financial Interests, Personal, Other, Travel accommodations: AstraZeneca Daiichi Sankyo, F Hoffmann-La Roche Ltd., Pfizer, Pierre-Fabre, Kern; Financial Interests, Personal and Institutional, Other, Contracted Research: AstraZeneca Daiichi Sankio; Financial Interests, Personal and Institutional, Invited Speaker, Contracted research: F Hoffmann-La Roche Ltd.; Financial Interests, Personal and Institutional, Other, Contracted research: Byondis, Zymeworks, Synthon, MedSir, Solti. A. Lopez Gonzalez: Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer; Financial Interests, Institutional, Advisory Board: Seagen. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca- Daiichi Sankyo, Pierre-Fabre, Pfizer; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi Sankyo; Non-Financial Interests, Invited Speaker: SOLTI. J. Ponce: Financial Interests, Personal, Advisory Board: Seattle Genetics, Novartis, AstraZeneca/Daiichi Sankyo, Roche; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, AstraZeneca/Daiichi Sankyo, Seattle Genetics, Lilly. O. Martínez-Sáez: Financial Interests, Personal, Advisory Board: Reveal Genomics. J.M. Cejalvo: Financial Interests, Institutional, Invited Speaker: Pfizer, Novartis. I. Blancas López-Barajas: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Lilly, Pfizer, Roche; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Novartis, Eisai, Celgene, Pfizer, Lilly, Pierre Fabre, Bristol Myers Squibb, Daiichi Sankyo, Grünenthal, Seagen, Veracyte; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, Roche, Novartis, Pfizer, Lilly, Pierre Fabre, Bristol Myers Squibb , Daiichi Sankyo. G. Villacampa: Financial Interests, Personal, Speaker’s Bureau: MSD, GSK, Pierre Fabre; Financial Interests, Personal, Advisory Role: AstraZeneca. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, 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; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Veracyte, Novartis; Financial Interests, Personal, Advisory Board: Roche, Genentech. All other authors have declared no conflicts of interest.