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Category: Breast Cancer

Weekly Top News – Breast Cancer – May 13, 2019

May 13, 2019

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo
Pivotal phase II DESTINY-Breast01 trial met primary endpoint, supporting global regulatory submission plan to start in H2 2019 (AstraZeneca Press Release) – May 7, 2019 – P2, N=230; DESTINY-Breast01 (NCT03248492); Sponsor: Daiichi Sankyo, Inc; “The HER2-targeting antibody drug conjugate (ADC) and potential new medicine was evaluated in patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine….The safety and tolerability profile of trastuzumab deruxtecan was also consistent with previous experience. These results are expected to support planned global regulatory submissions, including a Biologics License Application with the US Food and Drug Administration (FDA) anticipated in the second half of 2019.”

 

entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax
Entinostat: Interim OS analysis from P3 E2112 trial (NCT02115282) in combination with exemestane for advanced HR+ breast cancer in Q4 2019 (Syndax) – May 7, 2019 – Q1 2019 Results: Final OS analysis in Q2 2020
[Screenshot]

 

entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax
Entinostat: NDA submission for advanced HR+, HER2- breast cancer in 2020 (Syndax) – May 7, 2019 – Q1 2019 Results
[Screenshot]

 

Avastin (bevacizumab) / Roche; Tecentriq (atezolizumab) / Roche; Kadcyla (ado-trastuzumab emtansine) / Roche; Venclexta (venetoclax) / Roche, AbbVie; Perjeta (pertuzumab) / Roche; entrectinib (RXDX-101) / Roche
Roche to present new data highlighting comprehensive approach to cancer care at 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Roche Press Release) – May 10, 2019 – “Roche….announced that new data from clinical trials of 17 approved and investigational medicines across 27 cancer types, including hard-to-treat and rare tumours, will be presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, United States, from 31 May– 4 June, 2019. A total of 155 abstracts that include a Roche medicine will be presented at this year’s meeting.”

 

Herceptin Hylecta (trastuzumab/hyaluronidase-oysk) / Roche, Halozyme Therapeutics; pegvorhyaluronidase alfa (PEGPH20) / Halozyme Therapeutics
Halozyme reports first quarter 2019 results (PRNewswire) – May 7, 2019 – “‘We enjoyed a strong start to 2019 as our first quarter included a new ENHANZE® collaboration with argenx, positive phase III data from Janssen’s COLUMBA study evaluating a subcutaneous formulation of DARZALEX®, and FDA approval of Herceptin Hylecta™’….On ENHANZE® we anticipate regulatory submissions by ENHANZE® partner Janssen for the subcutaneous formulation of DARZALEX®, a new phase 3 trial initiation by one of our ENHANZE® partners and multiple Phase 1 trial initiations. On PEGPH20, we project the announcement of topline results from our HALO-301 pivotal phase 3 trial in pancreas cancer in the second half of the year.'”

 

Nerlynx (neratinib) / Puma
Puma Biotechnology reports first quarter 2019 financial results (Businesswire) – May 9, 2019 – “…’During 2019, we anticipate the following key milestones for Puma: (i) filing a new drug application for neratinib based on the results of the Phase III trial in third-line metastatic breast cancer in the summer of 2019; (ii) meeting with the FDA to discuss the clinical development and regulatory strategy for the SUMMIT trial in the summer of 2019; and (iii) receiving regulatory decisions for the extended adjuvant HER2-positive early stage breast cancer indication in other countries in the second half of 2019.”

 

Tecentriq (atezolizumab) / Roche; Herceptin (trastuzumab) / Roche; Perjeta (pertuzumab) / Roche
Genentech to present new data highlighting comprehensive approach to cancer care at 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) – May 10, 2019 – P3, N=900; IMpassion130 (NCT02425891); P3, N=808; CLEOPATRA (CLEOPATRA); Sponsor: Hoffmann-La Roche; “Key presentations in breast cancers: Key data to be presented at ASCO include…second interim analysis of overall survival (OS) results, updated safety data and patient-reported outcomes (PROs) from the Phase III IMpassion130 study of Tecentriq® (atezolizumab) plus chemotherapy (Abraxane…) for the treatment of PD-L1-positive, metastatic triple-negative breast cancer (TNBC)…Additional data include an eight-year, end-of-study analysis from the Phase III CLEOPATRA study of Perjeta® (pertuzumab) plus Herceptin® (trastuzumab) and chemotherapy for first-line treatment of HER2-positive metastatic breast cancer.”

 

Nerlynx (neratinib) / Puma
Puma Biotechnology reports first quarter 2019 financial results (Businesswire) – May 9, 2019 – P3, N=621; NALA (NCT01808573); P2, N=392; SUMMIT (NCT01953926); P2, N=650; CONTROL (NCT02400476); Sponsor: Puma Biotechnology; “…’During 2019, we anticipate the following key milestones for Puma: (i) presenting data from the Phase III trial of neratinib in third-line metastatic breast cancer patients in the second quarter of 2019; (ii) reporting additional data from the Phase II CONTROL trial in the second quarter of 2019; and (iii) reporting Phase II data from the SUMMIT basket trial in patients with HER2 mutations in the second half of 2019′.”

 

entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax
Syndax Pharmaceuticals reports fourth quarter 2018 financial results and provides clinical and business update (Syndax Press Release) – May 6, 2019 – P3, N=600; NCT02115282; “The Company continues to anticipate the next interim OS analysis for E2112, its NCI-sponsored, ECOG-ACRIN led Phase 3 registration trial of entinostat, a Class I selective HDAC inhibitor, plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer, in the second quarter of 2019. Additional interim analyses will be conducted by ECOG-ACRIN approximately every six months until either an OS benefit is observed, or the final target number of events occur. Any positive OS assessment would enable the Company to file for full regulatory approval.”

 

HLX02 (trastuzumab biosimilar) / Fosun Pharma
Henlius biosimilar HLX02 gets NDA acceptance from NMPA (Biospectrumasia) – May 8, 2019 – “Shanghai Henlius Biotech, Inc., subsidiary of Shanghai Fosun Pharmaceutical Group Co. has recently received a New Drug Application (NDA) acceptance from the National Medical Products Administration (NMPA) for its biosimilar HLX02, a trastuzumab for injection.”

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Weekly Top News – Breast Cancer – May 6, 2019

May 6, 2019

Tecentriq (atezolizumab) / Roche
Tecentriq clinical trial estimate: Updated OS data from P3 IMpassion031 trial (NCT03197935) for TNBC at ASCO 2019 (May 31 – June 4, 2019) (Cantor Fitzgerald) – May 3, 2019 – A subscription to Thomson ONE is required to gain full access to report 67171383; Page no: 1; REPORT TITLE: “Cantor daily research highlights”; AUTHOR: Research Department, et al; DATE: 04/24/2019

 

Tecentriq (atezolizumab) / Roche
GeparDouze/NSABP B-59: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy with atezolizumab or placebo in patients with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo (ESMO-BC 2019) – May 5, 2019 – Abstract #122TiP; Pres time: May 3, 2019; 12:15 PM – 01:00 PM; Location: Exhibition area; P3; “…Accrual will be 1,520 randomized patients stratified by region (North America; Europe), tumor size (1.1-3.0 cm; > 3.0 cm), epirubicin or doxorubicin/cyclophosphamide (EC; AC) schedule (q2w; q3w), and nodal status (positive; negative). Patients are randomized 1:1 to receive atezolizumab 1200 mg or placebo IV every 3 weeks concurrently with sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses and every 3 week carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 weeks (per investigator discretion) for 4 cycles…Main secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. GeparDouze is performed as an academic collaboration between NSABP and GBG.”

 

Ibrance (palbociclib) / Pfizer
Ibrance: Data from P3 PALLAS trial (NCT02513394) for HR+/HER2- breast cancer in H2 2020 (Pfizer) – Apr 30, 2019 – Q1 2019 Results: Data from P3 PENELOPE-B trial (NCT01864746) for breast cancer in H2 2020
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Keytruda (pembrolizumab) / Merck (MSD)
Keytruda: Data from P3 KEYNOTE-522 trial (NCT03036488) for TNBC in 2019 (Merck (MSD)) – Apr 30, 2019 – Q1 2019 Results: Data from P3 KEYNOTE-355 trial (NCT02819518) for 1L TNBC in 2019
[Screenshot]

 

Talzenna (talazoparib) / Pfizer
Impact of objective response (OR) on patient-reported outcomes (PRO) in patients (pts) with advanced breast cancer (ABC) and a germline BRCA1/2 (gBRCA) mutation in the phase III EMBRACA trial (ESMO-BC 2019) – May 5, 2019 – Abstract #154O; Pres time: May 2, 2019; 05:20 PM – 05:25 PM; Location: Vienna Hall; “…Background: In EMBRACA, a randomised 2:1 phase 3 open-label study of pts with ABC and a gBRCA mutation, a statistically significant higher OR rate was observed with talazoparib (TALA) (n = 219) vs physician’s choice of chemotherapy (PCT; n = 114) (62.6% vs 27.2%; odds ratio, 5.0; 95% CI, 2.9, 8.8; P < 0.001)… Overall change from baseline and greater delay in TTD in GHS/QoL were observed favouring pts who experienced OR vs those who did not have OR. These results suggest that higher OR rates may lead to better overall improvement from baseline and greater delay in TTD in GHS/QoL in pts with ABC and a gBRCA mutation.”

 

Kadcyla (ado-trastuzumab emtansine) / Roche
FDA approves Genentech’s Kadcyla for adjuvant treatment of people with HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment (Roche Press Release) – May 3, 2019 – “Genentech…announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla® (ado-trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant (before surgery) taxane and Herceptin® (trastuzumab)-based treatment…The FDA rapidly reviewed and approved the application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs…This approval is based on results of the Phase III KATHERINE study…”

 

Verzenio (abemaciclib) / Eli Lilly
Verzenio: Data from P2 monarcHER trial (NCT02675231) in metastatic breast cancer at the end of 2019 (Eli Lilly) – May 1, 2019 – Q1 2019 Results

 

capecitabine / generics; Avastin (bevacizumab) / Roche
Continuous chemotherapy improves outcomes and quality of life in advanced breast cancer [ESMO press release] (ESMO.org) – Apr 30, 2019 – P3, N=420; Stop&Go (NCT01935492); “The phase III study randomised 420 patients with advanced HER2-negative breast cancer to either an intermittent schedule (four cycles – ‘treatment holiday’ – another four cycles) or a continuous schedule comprised of the same eight cycles administered consecutively. Both first line treatment (paclitaxel plus bevacizumab) and second line treatment (capecitabine or non-pegylated liposomal doxorubicin) followed these schedules….Patients who started second line treatment (n=270; 131 vs. 139 in intermittent vs. continuous arms) demonstrated a median PFS in second line of 3.5 vs. 5.0 months respectively, with a hazard ratio (HR) of 1.04 (95%CI 0.69-1.57).”

 

Tecentriq (atezolizumab) / Roche
IMpassion031: A Study to Investigate Atezolizumab and Chemotherapy Compared With Placebo and Chemotherapy in the Neoadjuvant Setting in Participants With Early Stage Triple Negative Breast Cancer (clinicaltrials.gov) – Apr 29, 2019 – P3; N=324; Recruiting; Sponsor: Hoffmann-La Roche; Active, not recruiting –> Recruiting; N=204 –> 324; Trial completion date: Sep 2021 –> Jan 2023; Trial primary completion date: Mar 2019 –> Sep 2020

 

Prolia (denosumab) / Amgen, Daiichi Sankyo, GSK
A pragmatic, randomised, multicentre trial comparing 4-weekly vs. 12-weekly administration of bone-targeted agents (denosumab, zoledronate or pamidronate) in patients with bone metastases (ESMO-BC 2019) – May 5, 2019 – Abstract #LBA3; Pres time: May 2, 2019; 04:30 PM – 04:35 PM; Location: Vienna Hall; P4; “The findings of this trial are consistent with those previously reported for de-escalating ZA. This trial also included pts receiving de-escalated DN and PAM. While the results of the REDUSE trial are awaited, the data presented would suggest that de-escalation of commonly used BTAs is a reasonable treatment option.”

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Weekly Top News – Breast Cancer – April 29, 2019

April 29, 2019

Faslodex (fulvestrant) / AstraZeneca; SHR6390 / Jiangsu Hengrui Medicine

A Study of SHR6390 in Combination With Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer (clinicaltrials.gov) – Apr 25, 2019 – P3; N=288; Not yet recruiting; Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P3 trial

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo

DS-8201: Data from P3 DESTINY-Breast03 trial (NCT03529110) for HER2-positive, unresectable and/or metastatic breast cancer in 2020 or later (AstraZeneca) – Apr 26, 2019 – Q1 2019 Results: Data from P3 DESTINY-Breast04 trial (NCT03734029) for HER2-low, unresectable and/or metastatic breast cancer in 2020 or later
P3 data
[Screenshot]

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo

DS-8201: Regulatory submission in US for HER2 positive metastatic breast cancer in H1 FY 2019 (Daiichi Sankyo) – Apr 26, 2019 – FY 2018 Results: Regulatory submissions in Japan for HER2 positive metastatic breast cancer in H2 FY 2019, EU in H1 FY 2020
BLA • European regulatory • Japanese regulatory
[Screenshot]

 

Talzenna (talazoparib) / Pfizer

Pfizer receives positive CHMP opinion for Talzenna (talazoparib) for patients with inherited (germline) BRCA-mutated locally advanced or metastatic breast cancer (Pfizer Press Release) – Apr 26, 2019 – “Pfizer Inc….announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending TALZENNA® (talazoparib), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, be granted marketing authorization in the European Union (EU). The indication the CHMP adopted is for TALZENNA as monotherapy for the treatment of adult patients with germline breast cancer susceptibility gene (gBRCA)1/2-mutations, who have human epidermal growth factor receptor 2-negative (HER2-) locally advanced (LA) or metastatic breast cancer (MBC)….The Marketing Authorization Application was submitted based on results from the EMBRACA trial, the largest Phase 3 trial performed to date of a PARP inhibitor in patients with gBRCA-mutated LA or MBC.”
European regulatory

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo

DS-8201: Approval and launch in US/EU/Japan/Asia for HER2 positive breast cancer in FY 2020 (Daiichi Sankyo) – Apr 26, 2019 – FY 2018 Results
BLA • European regulatory • Japanese regulatory • Launch Europe • Launch Japan • Launch non-US • Launch US • Non-US regulatory
[Screenshot]

 

margetuximab (MGAH 22) / MacroGenics; Herceptin (trastuzumab) / Roche

SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). (ASCO 2019) – Apr 26, 2019 – Abstract #1000; Pres time: Jun 4, 2019; 09:45 AM – 09:57 AM; Location: Hall D1; No abstract available.
Clinical • P3 data

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo

DS-8201: Acceptance of regulatory submission in US for HER2 positive metastatic breast cancer previously treated with T-DM1 (based on DESTINY-Breast01 trial) in H2 2019 (AstraZeneca) – Apr 26, 2019 – Q1 2019 Results
BLA
[Screenshot]

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo

DS-8201: Data from P2 DESTINY-Breast01 trial (NCT03248492) for (HER2)-positive breast cancer in H2 2019 (AstraZeneca) – Apr 26, 2019 – Q1 2019 Results: Data from P3 DESTINY-Breast02 trial (NCT03523585) for pre-treated HER2 breast cancer in 2020 or later
P2 data • P3 data
[Screenshot]

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo

DS-8201: Data presentation from P2 DESTINY-Breast01 trial (NCT03248492) for (HER2)-positive breast cancer at SABCS (December 10-14, 2019) (Daiichi Sankyo) – Apr 27, 2019 – FY 2018 Results
P2 data
[Screenshot]

 

[fam-] trastuzumab deruxtecan (DS-8201) / Daiichi Sankyo; Keytruda (pembrolizumab) / Merck (MSD)

DS-8201 + Keytruda: Initiation of P1b trial for breast cancer in Q3 FY 2019 (Daiichi Sankyo) – Apr 26, 2019 – FY 2018 Results
New P1 trial
[Screenshot]

 

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Weekly Top News – Breast Cancer – April 22, 2019

April 22, 2019

Kisqali (ribociclib) / Novartis
In-depth gene expression analysis of premenopausal patients with HR+/HER2 advanced breast cancer (ABC) treated with ribociclib-containing therapy in the Phase III MONALEESA-7 trial. (ASCO 2019) – Apr 21, 2019 – Abstract #1018; Pres time: Jun 2, 2019; 08:00 AM – 11:00 AM; Location: Poster Board: 99, Hall A; No abstract available.
Clinical • P3 data

 

Kadcyla (ado-trastuzumab emtansine) / Roche; Perjeta (pertuzumab) / Roche
A phase III study comparing trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in elderly patients with advanced stage HER2-positive breast cancer: (JCOG1607 HERB TEA study). (ASCO 2019) – Apr 21, 2019 – Abstract #TPS1100; Pres time: Jun 2, 2019; 08:00 AM – 11:00 AM; Location: Poster Board: 181a, Hall A; No abstract available.
Clinical • P3 data

 

Afinitor (everolimus) / Novartis
Everolimus plus aromatase inhibitors vs aromatase inhibitors as maintenance therapy after first-line chemotherapy in HR+/HER2- metastatic breast cancer: final results of the Phase III randomized MAIN-A trial (ESMO-BC 2019) – Apr 18, 2019 – Abstract #LBA2; Pres time: May 3, 2019; 05:30 PM – 05:45 PM; Location: Maritim Hall; No abstract available.
Clinical • Late-breaking abstract • P3 data

 

Herceptin (trastuzumab) / Roche; Perjeta (pertuzumab) / Roche
End-of-study analysis from the phase III, randomized, double-blind, placebo (Pla)-controlled CLEOPATRA study of first-line (1L) pertuzumab (P), trastuzumab (H), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC). (ASCO 2019) – Apr 21, 2019 – Abstract #1020; Pres time: Jun 2, 2019; 08:00 AM – 11:00 AM; Location: Poster Board: 101, Hall A; No abstract available.
Clinical • P3 data

 

cisplatin/vinblastine formulation with cell penetration enhancer (INT230-6) / Intensity Therap
Intensity Therapeutics receives Fast Track Designation from U.S. FDA for development of INT230-6 as treatment for relapsed or metastatic triple negative breast cancer (GlobeNewswire) – Apr 17, 2019 – “Intensity Therapeutics…announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the Company’s development program evaluating INT230-6 for the treatment of patients with relapsed or metastatic triple negative breast cancer (TNBC) who have failed at least two prior lines of therapy….’we look forward to working closely with the FDA this year to initiate a Phase 2 clinical study for this indication.’”
Fast track designation • New P2 trial

 

Ibrance (palbociclib) / Pfizer
ROIS: UK Ibrance Patient Program (IPP) Study (clinicaltrials.gov) – Apr 19, 2019 – P; N=250; Not yet recruiting; Sponsor: Pfizer
Clinical • New trial

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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.”
sNDA

 

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.”
NICE

 

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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