123MO - BARBICAN: A randomized, phase II study to determine the contribution of ipatasertib to neoadjuvant chemotherapy plus atezolizumab in women with triple-negative breast cancer

Background

Pathological complete response (pCR) to neoadjuvant treatment in TNBC is strongly correlated with improved EFS and OS. Randomised trials have demonstrated increased pCR rates with the addition of checkpoint inhibitors to NACT in TNBC. Preclinical evidence suggests that AKT inhibition can enhance checkpoint inhibitor efficacy. The AKT inhibitor ipatasertib (IPAT) has shown promising activity in combination with paclitaxel as 1L therapy for metastatic TNBC. BARBICAN was designed to evaluate the clinical and biological effects of adding IPAT to NACT plus atezolizumab (atezo).

Methods

International phase II, randomised trial in 146 patients (pts) with newly diagnosed, non-metastatic, high risk (node+ and/or tumour size ≥2 cm) TNBC. Patients were randomised (1:1) to receive one cycle of atezo (1200mg Q3W) ± IPAT (400mg D1-14), followed by 3 cycles of atezo (840mg Q2W) + weekly paclitaxel (80mg/m²) ± IPAT (400mg D1-21), followed by 4 cycles of atezo (840mg Q2W) + dose-dense doxorubicin (60mg/m²)/cyclophosphamide (600 mg/m²). Tumour biopsies were obtained at baseline, after each treatment phase and surgery. The primary clinical endpoint was pCR rate (ypT0/is ypN0). PD-L1 expression was assessed using the SP142 assay (1% cut-off).

Results

144 pts received treatment, IPAT (n = 72) vs no ipatasertib (no-IPAT) (n = 72). There was no difference in pCR rates between treatment groups (chemo/atezo + IPAT, 49.3%, 95%CI, 36.8%-61.8%; chemo/atezo alone, 48.5%, 95%CI, 36.2%-61.0%). For IPAT vs no-IPAT, pCR was 66.7% vs 75.0% in the PD-L1-positive population (65 pts) and 32.4% vs 25.0% in the PD-L1-negative population (70 pts). pCR in node-positive pts was 55.6% (IPAT, 51.6%, no-IPAT 59.4%) compared to 43.1% (IPAT, 47.2%, no-IPAT 38.9%) in node-negative pts. Grade 3 or higher AE rates were 73.6% in the chemo/atezo + IPAT group and 40.3% in the chemo/atezo alone group, with rash, neutropenia, ALT increase, diarrhoea and mucosits being the most common. The majority of patients required IPAT dose modifications and the dose intensity was low.

Conclusions

Addition of IPAT to neoadjuvant atezo plus chemotherapy did not improve pCR rates. IPAT dose intensity was low due to increased toxicity.

Clinical trial identification

NCT03800836.

Editorial acknowledgement

Legal entity responsible for the study

Queen Mary University London.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Oncogenex; Financial Interests, Institutional, Research Grant: Roche; Other, Other, Spouse - Employee: Roche. B. Bermejo: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Palex; Financial Interests, Personal, Invited Speaker: AstraZeneca; Other, Personal, Member of the Board of Directors: GEICAM . M. Phillips: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer. D. Wheatley: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer. A. Llombart Cussac: Financial Interests, Stocks/Shares: MedSIR; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: EISAI; Financial Interests, Personal, Advisory Role: SEAGEN; Financial Interests, Personal, Advisory Role: Daiichi-Sanyo; Financial Interests, Personal, Advisory Role: Piere-Fabre; Financial Interests, Personal, Advisory Role: Agendia; Financial Interests, Research Grant: Roche; Financial Interests, Research Grant: Eli Lilly; Financial Interests, Research Grant: EISAI; Financial Interests, Research Grant: GSK; Financial Interests, Research Grant: Novartis; Financial Interests, Research Grant: Pfizer; Financial Interests, Research Grant: Agendia; Financial Interests, Research Grant: Genomic-Health; Financial Interests, Research Grant: AstraZeneca; Other, Other, Travel, accomodation, expenses: Roche; Other, Other, Travel, accomodation, expenses: Pfizer; Other, Other, Travel, accomodation, expenses: Eli Lilly. E. Zamora: Financial Interests, Personal, Training, Company internal training session: Novartis; Other, Personal, Other, Travel and accomodation to assist ESMO congresse: Pfizer; Other, Personal, Other, Travel and accomodation to assist ESMO congresse: Roche; Other, Personal, Other, Travel and accomodation to assist post-SABCS congresse: Lilly. G. Viale: Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Advisory Board: Dako; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Ventana Medical Systems; Financial Interests, Institutional, Research Grant: Dako/Agilent; Financial Interests, Institutional, Research Grant: Cepheid; Other, Personal, Other, Travel: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: MSD Oncology. S. Kuemmel: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Somatex; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Genomic Health; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: PFM Medical; Financial Interests, Personal, Speaker’s Bureau: Celegene; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Somatex; Financial Interests, Personal, Speaker’s Bureau: Sonoscape; Financial Interests, Personal, Speaker’s Bureau: Seagen; Other, Other, Support for attending mettings and/or travel: Roche; Other, Other, Support for attending mettings and/or travel: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: PFM Medical; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Somatex; Other, Personal, Leadership Role: WSG; Other, Personal, Leadership Role: AGO. J. Cortés: Financial Interests, Personal, Advisory Board: 4D Pharma PLC; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: Bioasis; Financial Interests, Personal, Advisory Board: Biothera; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Advisory Board: Cellestia; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Erytech; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Kyowa Kyrin; Financial Interests, Personal, Advisory Board: Leuko; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Polyphor; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Samsung Bioepis; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Research Grant: Bayer Healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Guardanth Health; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma B; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Financial Interests, Institutional, Research Grant: Roche; Other, Personal, Other, Travel cost and expenses: Daiichi Sankyo; Other, Personal, Other, Travel cost and expenses: Eisai; Other, Personal, Other, Travel cost and expenses: Novartis; Other, Personal, Other, Travel cost and expenses: Roche. All other authors have declared no conflicts of interest.