1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

Clinical endpoint

Vinorelbine

Triple-negative breast cancer

Eribulin

Interim analysis

10.1200/jco.2021.39.15_suppl.1077

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Figure S1 from High FGFR1–4 mRNA Expression Levels Correlate with Response to Selective FGFR Inhibitors in Breast Cancer

Mònica Sánchez-Guixé Cinta Hierro J. L. Jiménez Cristina Viaplana Guillermo Villacampa

Supplementary Figure 1. FGFR1-4 DNA CN, mRNA levels and ROC curves analysis. A) Waterfall plot representing the best antitumor response of FGFRi in 24 patients from 8 different cancer types treated at VHIO. FGFR1/2 amplification status and high FGFR1-4 mRNA levels are indicated in the underneath panel. B) Copy number (CN) values of FGFR1-4 by MSK-IMPACT in the FGFR/FGFamp PDX collection and categorized analysis in PDXs harboring CN amplification (CN>4), according to the response to rogaratinib (responders (SD and PR) and non-responders (PD)). C) Evaluation of FGFR1/4 CN ratio by FISH ratio (the dashed line indicates the CN ratio>2.2 that is considered amplified) and categorized analysis according to the response to rogaratinib. D) Correlation analysis between the CN values (X-axis) and mRNA levels (Y-axis) of FGFR1-4 obtained from MSK-IMPACT or nCounter, respectively. Pearson correlation coefficient (r2) is shown. E) Categorized analysis of FGFR1-4 mRNA composite biomarker according to the response to rogaratinib, obtained from HTG or qPCR data. Statistical test: Mann-Whitney U test. ROC curve analysis the FGFR1-4 mRNA composite biomarker, obtained from HTG or qPCR (AUC=0.89, both).

10.1158/1078-0432.22483824.v1

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Supplementary Data from Independent Validation of the PAM50-Based Chemo-Endocrine Score (CES) in Hormone Receptor–Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti–HER2-Based Therapy

Tomás Pascual Aranzazu Fernandez-Martinez Maki Tanioka Maria Vittoria Dieci Sònia Pernas

Supplementary Data

Neoadjuvant Therapy

10.1158/1078-0432.22481012.v1

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Supplementary Table from Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification

Benedetta Pellegrino Andrea Herencia-Ropero Alba Llop‐Guevara Flaminia Pedretti Alejandro Moles‐Fernández

Supplementary Table from Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification

Stratification (seeds)

Identification

10.1158/0008-5472.22431336

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Supplementary Fig 4 from Phase Ib Dose-escalation/Expansion Trial of Ribociclib in Combination With Everolimus and Exemestane in Postmenopausal Women with HR+, HER2− Advanced Breast Cancer

Aditya Bardia Shanu Modi Mafalda Oliveira Javier Cortés Mario Campone

Supplementary Fig 4

Exemestane

Everolimus

10.1158/1078-0432.22477824

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Figure S2 from POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients

Richard D. Baird Annelot G.J. van Rossum Mafalda Oliveira Karin Beelen Meiling Gao

Pharmacokinetics: Z-endoxifen levels per taselisib dose level

BETA (programming language)

10.1158/1078-0432.22471986.v1

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Interim analysis (IA) of the giredestrant (G) + everolimus (EVERO) arm in MORPHEUS Breast Cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC).

Journal of Clinical Oncology (2024)

Seth A. Wander Salomon M. Stemmer Hope S. Rugo Seock‐Ah Im Peter K. H. Lau

1059 Background: Endocrine therapy (ET) + a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is a therapeutic mainstay for first-line tx of ER+ mBC. Finding effective ET combinations after progression remains a challenge; however, targeting the Akt/mTOR pathway is a promising approach. G is a highly potent, non-steroidal, oral (PO), selective ER antagonist and degrader that is well tolerated and achieves robust ER occupancy. EVERO is an approved mTOR inhibitor. Here, we present a 16-week IA of the G + EVERO arm in MORPHEUS BC (NCT04802759). Methods: Eligible pts with disease progression on 1–2 lines of ET (including a CDK4/6i) for LA/mBC were randomized 1:6 to receive G (30 mg PO daily [QD]) or G + EVERO (10 mg PO QD) until disease progression (PD)/unacceptable toxicity. The study was not designed to make explicit power and type I error considerations for a hypothesis test. Primary endpoints were safety and objective response rate (ORR); other endpoints included progression-free survival (PFS), overall survival, clinical benefit rate, disease control rate (DCR), duration of response, and pharmacokinetics. Steroid mouthwash was recommended for prophylaxis or treatment. Genetic alterations were defined using baseline circulating tumor DNA. Results: Results for the G arm have been presented previously and are not included here. As of July 24, 2023, 15 pts were enrolled in the G + EVERO arm: 66.7% and 33.3% received 1–2 prior lines of therapy for LA/mBC, respectively; 26.7% had prior fulvestrant, and 73.3% had liver metastasis at enrollment. One pt had prior capecitabine. Safety data are in the table. Confirmed ORR in the G + EVERO arm was 26.7% (n = 4). Partial responses were reported in 26.7% of pts (n = 4; all had ESR1 mutations, 1 also had an Akt pathway mutation), 46.7% of pts (n = 7) had stable disease, and the DCR was 53.3% (n = 8). Median PFS was not reached at data cutoff. No clinically relevant drug–drug interactions were observed. Conclusions: Safety of G + EVERO was aligned with the individual safety profile of each drug with no overlapping toxicities or new safety signals seen. An encouraging efficacy signal was observed with G + EVERO in pts with PD on 1–2 lines of ET (including a CDK4/6i). G + EVERO is being further investigated in the Phase III evERA BC trial (NCT05306340). Clinical trial information: NCT04802759 . [Table: see text]

Everolimus

Interim analysis

Interim

10.1200/jco.2024.42.16_suppl.1059

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Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Zhen Shi Julia Wulfkuhle Małgorzata Nowicka Rosa I. Gallagher Cristina Saura

Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Triple-negative breast cancer

Complete response

10.1158/1078-0432.22483011.v1

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Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Zhen Shi Julia Wulfkuhle Małgorzata Nowicka Rosa I. Gallagher Cristina Saura

Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Triple-negative breast cancer

Neoadjuvant Therapy

Complete response

10.1158/1078-0432.22483014.v1

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Abstract OT2-06-01: Solti-1903 HOPE: Real-world clinical practice study to assess the impact of using genomic data on the next treatment decision making-choice in patients with locally advanced or metastatic breast cancer in Spain

Cancer Research (2022)

Ana Casas Eva Ciruelos Mafalda Oliveira Cristina Saura Meritxell Bellet

Abstract BACKGROUND: Metastatic breast cancer (mBC) remains an incurable disease and is the cause of nearly all deaths related to BC. Next-generation sequencing technologies are allowing the application of personalized targeted molecular therapies, thereby improving outcomes in breast cancer patients. However, they are not routinely used in the clinic and their cost could be a cause of disparity. One strategy to overcome the barriers of implementing NGS in the clinic is to promote the active participation of patients with mBC in the management of their disease and offering free access to these tests. With this in mind, we designed HOPE (SOLTI-1903), a Spanish real-world study where patients lead their inclusion, participation, and follow-up through a digital tool (DT) that guides them in every step of the journey. The ultimate objective of HOPE is to gather real-world data on the utilization of molecular information in the management of mBC and to empower these patients. TRIAL DESIGN: Patients diagnosed with locally advanced or mBC can be included. Basic demographic data, disease characteristics, treatment history and quality of life data are collected by patients through a DT. The study is complemented by a patient empowerment program including informative workshops and precision medicine video-tutorials. Patients are encouraged to involve their physicians in HOPE. A total of 600 patients will be included in Spain. PATIENT JOURNEY: Once patients request participation through the DT, a dedicated team in SOLTI assists them in the subsequent steps while validating that eligibility criteria are met according to patient-provided data. Then, patients receive instructions from SOLTI’s team to attend the nearest partner local laboratory, where they sign the study informed consent form. A metastatic (preferably) or primary archival tumor sample is requested from the patient’s reference hospital and analyzed by FoundationOne®CDx. Patients that are in progression or not receiving active systemic chemo- or radiotherapy undergo a blood draw to receive a Guardant360 analysis. These two NGS tests are offered to all patients, and the blood test is performed even if no tissue is available. The results from the molecular analyses are regularly reviewed by a Molecular Advisory Board (MAB). The MAB, based on its joint experience in clinical oncology, genomics, bioethics, and pathology, may add some advice to these reports via DT, making comments about detected molecular alterations and adding further recommendations for specific treatment options or available CT with targeted therapies and/or additional genetic tests such as germline validation of potentially significant findings. From that moment, patients are requested to record their disease evolution in the DT every 3 months for 2 years. The primary objective is to assess the real-world clinical practice integrating molecular profiling in the Standard of Care management of patients with mBC connected through a DT. Secondary objectives include to i) describe the genetic mutational profile of mBC, ii) estimate the enrollment rate in CT of patients engaged in a patient-centered strategy for molecular tumor assessment, iii) assessing Progression Free Survival, Overall Survival and Quality of Life status among patients enrolled in CT according to the tumor’s genomic profile and iv) evaluate the logistic feasibility of the study. Recruitment started on October 2020. By June 2021, 362 patients had been enrolled. ACKNOWLEDGEMENTS: This study is sponsored by SOLTI and financially supported by Novartis and three non-profit organizations: Asociación Cáncer de Mama Metastásico, Asociación Saray and Fundación Actitud frente al Cáncer. Roche and Guardant Health provide their tests for all patients. Citation Format: Ana Casas, Eva Ciruelos, Mafalda Oliveira, Cristina Saura, Meritxell Bellet, Sonia Pernas, Joaquín Gavilá, Montserrat Muñoz, Maria Vidal, Blanca González-Farré, Juan M. Cejalvo, Rafael López, Ana Vivancos, Marcos Malumbres, Javier Salvador Bofill, Isabel Blancas, Emilio Alba, Valentina Boni, Susana De la Cruz, Elena Galve, Antonia Perelló, Mireia Margelí, Meritxell Soler, Rubén Olivera-Salguero, Helena Masanas, Rosa Olmos, Marga Forns, Pilar Fernández Pascual, Elia Seguí, Tomas Pascual, Aleix Prat. Solti-1903 HOPE: Real-world clinical practice study to assess the impact of using genomic data on the next treatment decision making-choice in patients with locally advanced or metastatic breast cancer in Spain [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-06-01.

10.1158/1538-7445.sabcs21-ot2-06-01

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