P. Villagrasa (Barcelona, Spain)

SOLTI Breast Cancer Research Group

Author Of 3 Presentations

 On-Demand ePoster Display

40TiP - SOLTI-1802 ONAWA Trial: A Window of Opportunity Trial of Onapristone (ONA) in Postmenopausal Women with Estrogen and Progesterone Receptor-Positive/HER2-negative (ER+/PgR+/HER2-) Early Breast Cancer (EBC)

Abstract

Background

PgR expression is a biomarker of ER functionality, cellular progression to malignancy, and response to endocrine therapy (ET) in HR+ BC. ONA, a type I antiprogestin showed activity in patients with metastatic BC, but early trials with its immediate release formulation showed liver toxicity and further studies were halted. The development of a new extended-release formulation (Context Therapeutics, PA, USA), which is associated with a lower liver toxicity (Cottu PH, PLOS ONE, 2018) has strongly supported the relaunching of ONA clinical development. ONA blocks Ser294 phosphorylation of PgR, a posttranslational event associated with elevated PgR transcriptional activity coupled to rapid PgR turnover and also, downregulates PgR gene targets both in tumor cells expressing a sumo-deficient/phospho-mimic activated (KR) and non-activated (WT) PgR phenotype, independent to the presence of progesterone. Considering BC heterogeneity and that PgR analysis by standard immunohistochemistry (IHC) does not perfectly correlate with PgR target gene expression, the identification of biomarkers allowing the selection of patients with PgR-driven tumors that may benefit from antiprogestins treatment is currently an unmet need.

Trial design

ONAWA is an open-label, single arm, multicenter window of opportunity clinical trial of ONA (50 mg extended-release tablets BID for 21 days) for postmenopausal women with EBC amenable to receive a short course of ET before surgery. Ten patients with ER+/PgR+/HER2- and ki67 ≥ 15% BC will be enrolled at 4 sites of the SOLTI network. The primary objective is to evaluate the biological activity of ONA by the rate of Complete Cell Cycle Arrest determined by Ki67 (≤2.7%). Secondary endpoints include safety and correlating biological activity with IHC of tumor expression (ER, PgR, Ser294-PgR, CD24, CD44, ALDH1, Ki67), estradiol, and progesterone blood levels, and gene expression profile (NanoString nCounter® Breast 360TM panel). The study was approved in July 2020 and recruitment started in November 2020. Seven patients have been enrolled at the time of this submission.

Clinical trial identification

NCT04142892; EudraCT Number: 2019-001433-13.

Legal entity responsible for the study

SOLTI Breast Cancer Research Group.

Funding

Context Therapeutics.

Disclosure

X. González-Farré: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Eisai; Honoraria (self): SOLTI. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self): NanoString; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Puma. C. Saura Manich: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Hoffman-La Roche; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Genomic Health; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sharp and Dhome España SA; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Philips Healthwork; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: prIME Oncology; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Puma; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Synthon; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi Aventis. All other authors have declared no conflicts of interest.

Collapse

73TiP - SOLTI1710 PROMETEO II: Palbociclib in combination with letrozole in Hormone Receptor-positive (HR+)/HER2-negative residual disease after standard neoadjuvant chemotherapy (NAC)

Abstract

Background

The combination of cyclin-dependent kinase inhibitors (CDK4/6i) with first or second-line endocrine therapy are the standard of care for HR+/HER2-negative metastatic breast cancer (BC); its role in the early-setting is being evaluated in several studies with discordant results. In HR+/HER2-negative BC, pathologic complete response (pCR) rates after NAC are around 15%. Additional therapeutic strategies to eradicate these residual tumor cells are needed. To characterize the biological effect of CDK4/6i in residual disease (RD) after NAC, could help to better understand their role in early BC.

Trial design

SOLTI-1710 PROMETEO II is an open-label, multicenter window of opportunity trial of Palbociclib and letrozole tested in patients with HR+/HER-negative RD after completing anthracycline/taxane-based NAC. PROMETEO II will include 22 patients. Invasive RD must be confirmed by core-biopsy and have a diameter ≥ 10mm measured by ultrasound. Adequate organ function and ECOG PS 0-1 are required. A short course of Palbociclib is administered at a dose of 125 mg/day for 21 days and letrozole 2.5 mg/day continuously until surgery. BC surgery is carried out 1 week after the last dose of palbociclib. The primary objective of the trial is to evaluate the antitumor activity by the Complete Cell Cycle Arrest (CCCA) rate determined by Ki67 ≤2.7%, centrally assessed at surgery. Secondary endpoints include pCR rate, RCB and safety. To date, 12 patients have been included at 8 sites in Spain.

Clinical trial identification

NCT04130152.

Legal entity responsible for the study

SOLTI.

Funding

Pfizer.

Disclosure

E. Ciruelos: Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD. X. González-Farré: Advisory/Consultancy: SOLTI Breast Cancer Group; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Advisory/Consultancy: Eisai. P. Villagrasa: Honoraria (self): NanoString. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Research grant/Funding (self): NanoString Technologies; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Amgen; Advisory/Consultancy: PUMA. S. Pernas Simon: Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Polyphor; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.

Collapse

130TiP - SOLTI-1303 PATRICIA II randomized phase II trial of palbociclib plus trastuzumab and endocrine therapy (ET) versus treatment of physician's choice (TPC) in metastatic HER2-positive and hormone receptor-positive (HER2+/HR+) breast cancer (BC) with PAM50 luminal intrinsic subtype

Abstract

Background

PATRICIA phase II trial showed that Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated HER2+/HR+ advanced breast cancer with a PAM50 Luminal A or B subtype (Ciruelos E. et al, CCR 2020). Based on these results, PATRICIA II was designed to include only patients with HER2+/HR+, PAM50 Luminal A/B tumors to receive palbociclib, trastuzumab and ET versus treatment of physician’s choice (TPC).

Trial design

PATRICIA II is a randomized open-label, adaptive design, phase II study. Patients must have centrally confirmed HER2+/HR+ and PAM50 Luminal A or B tumors and have received at least 1 (and no more than 4) prior lines of anti-HER2 regimens for locally advanced or metastatic BC. Patients are randomized 1:1 to receive trastuzumab plus palbociclib at a standard dose of 125 mg/day orally 3 weeks on/ 1 week off and ET (Cohort C1) or TPC (cohort C2). ET options in cohort 1 are either an aromatase inhibitor, fulvestrant or tamoxifen +/- ovarian suppression. TPC options in cohort C2 are T-DM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin, paclitaxel or docetaxel) plus trastuzumab. Stratification factors include number of previous regimens for advanced or metastatic BC (1-2 vs 3-4) and the presence of visceral disease (yes vs no). Primary endpoint is to compare the progression-free survival between two arms. The study has an 80% power with two-sided alpha=0.05 to detect a HR of 0.62 in favor of the palbociclib cohort. Secondary endpoints include response rate, overall survival, safety, and quality of life. Tumor tissue and blood samples will be collected for biomarker analyses. An estimated total of 516 patients will be screened to include 232 patients with HER2+/HR+ PAM50 Luminal A or B tumors. The recruitment is ongoing in 20 sites in Spain and as of February 3rd, 2021, 107 patients were screened and 30 were enrolled in the trial.

Clinical trial identification

NCT02448420.

Legal entity responsible for the study

SOLTI.

Funding

Pfizer.

Disclosure

E.M. Ciruelos: Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD. S. Pernas Simon: Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Polyphor; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Roche. M. Oliveira: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Philips Healthcare; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Immunomedics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Zenith Epigenetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Puma Biotechnology; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: Eisai. B. Bermejo De Las Heras: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Palex; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. X. González-Farré: Advisory/Consultancy: SOLTI Breast Cancer Group; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Advisory/Consultancy: Eisai. P. Villagrasa: Honoraria (self): NanoString. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self): NanoString Technologies; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Puma. All other authors have declared no conflicts of interest.

Collapse