124O - Patritumab deruxtecan (HER3-DXd) in hormonal receptor-positive/HER2-negative (HR+/HER2-) and triple negative breast cancer (TNBC): results of part B of SOLTI TOT-HER3 window of opportunity trial

Background

We previously reported the biologic and clinical activity of HER3-DXd in Part A of SOLTI TOT-HER3 in patients (pts) with HR+/HER2- early breast cancer (BC) after a single dose of 6.4 mg/kg (Prat A. et al, ESMO BREAST 2022). Here, we present the main efficacy and safety results of TOT-HER3 Part B.

Methods

In Part B of this window of opportunity trial, 2 cohorts of pts with treatment-naïve HER2- primary operable BC, ≥1 cm by US or MRI were recruited. Pts received a single dose of HER3-DXd 5.6 mg/kg. Primary objective was the variation in tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) score between pre- and post-treatment tumors. Associations of baseline clinical and biological features with CelTIL changes and overall response rate (ORR) by US were explored.

Results

Thirty-seven pts with HER2- BC were recruited (HR+ n=20; TNBC n=17). Mean age was 53 (30-81); 20 (54%) were pre-menopausal; mean tumor size was 21 mm (range 10-81 mm); and median Ki67 was 30% (12-95%). In response to treatment with HER3-DXd CelTIL score increased and decreased in 21 (57%) and 16 (43%) pts, respectively. Overall, a statistically significant change in CelTIL was observed between paired samples overall (p=0.046) and in TNBC (p=0.016), but not in HR+ (p=0.793). ORR by US in all patients was 32% (35% in TNBC and 30% in HR+). The absolute change in CelTIL was associated with ORR (AUC=0.693; p=0.049). Baseline ERBB3 levels were not associated with CelTIL change or ORR. HER3-DXd induced high expression of immune-related genes (e.g., PD1, CD8 and CD19), and suppressed proliferation-related genes. Thirty-one (84%) patients reported AEs at any grade. Most common AEs were nausea, fatigue, alopecia, diarrhea, constipation and vomiting. Grade 3 treatment-related nausea occurred in 1 patient. No ILD events were reported.

Conclusions

A single dose of HER3-DXd was associated with clinical response and significant biological changes in HER2- tumors, irrespective of baseline ERBB3 levels. The safety profile was consistent with that previously reported. Additional correlative analysis will be presented on site.

Clinical trial identification

EudraCT 2019-004964-23. NCT04610528, First posted: October 30, 2020.

Legal entity responsible for the study

SOLTI Cancer Research Group.

Funding

Daiichi Sankyo Inc.

Disclosure

M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Pierre Fabre, Roche, Seagen, iTEOS, Relay Therapeutics; Financial Interests, Personal, Invited Speaker: Gilead, MSD, Novartis, Pfizer, Roche, Seattle Genetics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech. 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. M. Margeli Vila: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Novartis, MSD, Gilead, Lilly, Pierre Fabre; Financial Interests, Personal, Other, Travel expences: Gylead; Financial Interests, Institutional, Invited Speaker, I have received research funding for my institution from Pfizer: Pfizer. J.M. Cejalvo: Financial Interests, Institutional, Invited Speaker: Pfizer, Novartis. J. Cruz Jurado: Financial Interests, Personal, Advisory Board: PharmaMar, Roche, Lilly, Pfizer, Novartis, Gilead, AstraZeneca, Daiichi, Seagen, GSK, Bayer; Financial Interests, Personal, Invited Speaker: PharmaMar, Roche, Lilly, Pfizer, Novartis, Eisai, Gilead, AstraZeneca, Daiichi, Seagen, Esteve, Roche. M.J. Vidal Losada: Financial Interests, Personal, Advisory Board: Novartis/Pfizer, Roche, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis/Pfizer, Roche/Genentech, AstraZeneca/Daiichi Sankyo, Gilead Sciences; Financial Interests, Personal, Other, Travel, Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences. 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: Astra-Zeneca, Novartis, Daiichi Sankyo; Non-Financial Interests, Invited Speaker: SOLTI. S. Esker, P. Fan, A. Santhanagopal: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. O. Martínez-Sáez: Financial Interests, Personal, Advisory Board: Reveal. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. R. Sanchez Bayona: Financial Interests, Personal, Invited Speaker: Novartis, Lilly Oncology, GSK Oncology, AstraZeneca, Seagen, Clovis Oncology; Financial Interests, Personal, Other, Travel and accommodation: Pfizer; Financial Interests, Personal, Full or part-time Employment, Medical Advisor: SOLTI; Financial Interests, Personal, Other, Medical Monitor in HARMONIA Trial: Novartis. C. Falato: Financial Interests, Personal, Expert Testimony, Study results presentation for educational purposes: Daiichi Sankyo. 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. All other authors have declared no conflicts of interest.