Weekly Top News – Breast Cancer – April 9, 2019

April 9, 2019

Ibrance (palbociclib) / Pfizer
U.S. FDA approves Ibrance (palbociclib) for the treatment of men with HR+, HER2- metastatic breast cancer (Businesswire) – Apr 4, 2019 – “Pfizer…announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indications for IBRANCE® (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. The approval is based on data from electronic health records and postmarketing reports of the real-world use of IBRANCE in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database and the Pfizer global safety database.”


Verzenio (abemaciclib) / Eli Lilly
NICE nod for Lilly’s breast cancer drug Verzenio via CDF (PMLive) – Apr 2, 2019 – “Thousands of women with advanced breast cancer could get access to treatment with Eli Lilly’s CDK 4/6 inhibitor Verzenio, after NICE backed its use via the Cancer Drugs Fund (CDF). The cost-effectiveness watchdog has opted to make Verzenio (abemaciclib) plus fulvestrant available to around 4,800 women with hormone receptor (HR) positive, HER2-negative breast cancer which has spread to other parts of the body, provided they have already received endocrine treatment.”


U3-1402 / Daiichi Sankyo; Herceptin (trastuzumab) / Roche
U3-1402, a novel HER3-targeting antibody-drug conjugate, exhibits its antitumor activity through increased payload intracellular delivery via highly efficient drug internalization (AACR 2019) – Apr 5, 2019 – Abstract #LB-275/21; Pres time: Apr 3, 2019; 08:00 AM – 12:00 PM; Location: Section 40; “…U3-1402 is a novel HER3-targeting antibody-drug conjugate (ADC) consisting of a fully human anti-HER3 antibody (patritumab), a tetrapeptide-based linker, and a topoisomerase I inhibitor payload…In vitro molecular dynamics were compared between U3-1402 and trastuzumab (anti-HER2 antibody) using the MDA-MB-453 cell line, which expresses both HER2 and HER3… U3-1402 has a high internalization property for effective payload delivery to HER3-expressing cancer cells, resulting in a favorable ADC-driven efficacy.”
Late-breaking abstract


Verzenio (abemaciclib) / Eli Lilly; Ibrance (palbociclib) / Pfizer; Kisqali (ribociclib) / Novartis
Multi-omics profiling establishes the polypharmacology of FDA Approved CDK4/6 inhibitors and its impact on drug response (AACR 2019) – Apr 5, 2019 – Abstract #4432/26; Pres time: Apr 2, 2019; 01:00 PM – 05:00 PM; Location: Section 37; “We find that the three drugs differ at a cellular level and that abemaciclib has targets and activities not shared by palbociclib or ribociclib including: induction of cell death (even in pRb-deficient cells), arrest in the G2 phase of the cell cycle, reduced drug adaptation, and unique transcriptional effects in vitro and in vivo. These activities appear to arise from inhibition of CDKs other than CDK4/6 including CDK2/Cyclin A/E and CDK1/Cyclin B. We propose that inhibition of these kinases by abemaciclib target known mechanisms of resistance to CDK4/6 inhibition and thus elicit a response in cell lines that are resistant to palbociclib or ribociclib.”
FDA event


Zoladex (goserelin acetate implant) / AstraZeneca, TerSera Therap; Kisqali (ribociclib) / Novartis; Arimidex (anastrozole) / AstraZeneca, Remedica
Genetic landscape of premenopausal HR+/HER2- advanced breast cancer (ABC) based on comprehensive circulating tumor DNA analysis and association with clinical outcomes in the Phase III MONALEESA-7 trial (AACR 2019) – Apr 5, 2019 – Abstract #CT141/7; Pres time: Apr 2, 2019; 08:00 AM – 12:00 PM; Location: Section 16; P3; “…The Phase III MONALEESA-7 study (NCT02278120), the first trial of endocrine therapy ± a cyclin-dependent kinase 4/6 inhibitor for premenopausal patients (pts) with HR+/human epidermal growth factor receptor 2-negative (HER2-) ABC, demonstrated that the addition of ribociclib (RIB) to a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen (TAM) + goserelin (GOS) significantly extended progression-free survival (PFS; Tripathy D, et al…We conducted a comprehensive ctDNA genomic analysis from MONALEESA-7. Premenopausal pts with HR+/HER2- ABC were randomized 1:1 to RIB or placebo (PBO) + NSAI (letrozole [LET] or anastrozole) or TAM + GOS… RIB + NSAI/TAM + GOS provided PFS benefit irrespective of baseline biomarker alteration status and represents recommended first-line therapy for pts with premenopausal HR+/HER2- ABC. The genetic landscape of premenopausal ABC might modulate the magnitude of therapeutic benefit; these novel findings require confirmation in…”
Clinical • Clinical data • P3 data


Ibrance (palbociclib) / Pfizer
Tyrosine phosphorylation of p27Kip1 associates with Palbociclib responsiveness in breast cancer (AACR 2019) – Apr 5, 2019 – Abstract #LB-224/3; Pres time: Apr 2, 2019; 01:00 PM – 05:00 PM; Location: Section 41; “Thus, we hypothesized the pY88-p27 status may serve as a biomarker for patients that can respond to cdk4i therapy. We analyzed paraffin-embedded archival breast cancer biopsies from a 13 patient cohort of HR+, Her2- patients who had received Palbociclib/Letrozole in the front line metastatic setting. Our data suggest that pY88-p27 status, as a surrogate marker for cdk4 activity, associates with responsiveness to CDK4i treatment. Clinical use of the pY88 biomarker may identify patients responsive or resistant to Cdk4 targeting drugs.”
Late-breaking abstract


sacituzumab govitecan (IMMU-132) / Immunomedics
Study of IMMU-132 in HR+/HER2- MBC (TROPICS-02) (clinicaltrials.gov) – Apr 3, 2019 – P3; N=400; Not yet recruiting; Sponsor: Immunomedics, Inc.
Clinical • New P3 trial


Ibrance (palbociclib) / Pfizer
Molecular analysis for therapy choice (NCI-MATCH, EAY131) arm Z1B: Phase II trial of palbociclib for CCND1, 2 or 3 amplified tumors (AACR 2019) – Apr 5, 2019 – Abstract #LB-010/2; Pres time: Mar 31, 2019; 01:00 PM – 05:00 PM; Location: Section 41; “In a cohort of heavily pretreated pts with non-breast solid tumors selected for CCND1, 2 or 3 amplification and treated with palbociclib, prolonged stable disease was noted in 13% of patients. CCND1 or 3 amplification may not predict response to palbociclib in this cohort. No new palbociclib-related safety signals were observed.”
Biomarker • Late-breaking abstract • P2 data


Herceptin (trastuzumab) / Roche
NBE-002, an anthracycline-based immune-stimulatory antibody drug conjugate (iADC) targeting ROR1 for the treatment of triple-negative breast cancer (AACR 2019) – Apr 5, 2019 – Abstract #LB-197/15; Pres time: Apr 2, 2019; 08:00 AM – 12:00 PM; Location: Section 42; “…Anti-tumor activity of PNU-ADCs involved activation of the immune system, as shown by evaluation of NBE-002 or a Trastuzumab-PNU conjugate (T-PNU) in ROR1- or HER2-positive syngeneic breast cancer models, respectively… Our results demonstrate that NBE-002 is a highly effective and promising targeted therapeutic for the treatment of ROR1 positive TNBC and potentially other solid tumor indications that warrants clinical development. Considering the pronounced immune-modulatory functions of the PNU payload, NBE-002 may be particularly well suited for combination therapy with immune checkpoint inhibitors. NBE-002 is currently undergoing GMP manufacturing and initiation of clinical studies is expected in mid-2020.”
Late-breaking abstract


Nerlynx (neratinib) / Puma
Puma Biotechnology and Pierre Fabre enter into exclusive license agreement to develop and commercialize Nerlynx (neratinib) in Europe (Businesswire) – Apr 1, 2019 – “Puma Biotechnology…and Pierre Fabre have entered into an exclusive license agreement under which Pierre Fabre will develop and commercialize NERLYNX® (neratinib) within Europe and part of Africa…Pierre Fabre will have exclusive commercialization rights for NERLYNX in European countries excluding Russia and Ukraine, along with countries in North Africa and francophone countries of West Africa. Pierre Fabre will also be responsible for conducting additional clinical studies and leading regulatory activities in connection with the European Medicines Agency (EMA).”
Licensing / partnership


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