Onco Actu du 10 décembre 2019

	2.6 ETIOLOGIE - ENVIRONNEMENT
Austrian leader blocks ban on weedkiller glyphosate, citing technicality [Reuters] Chancellor Brigitte Bierlein, a career judge who must sign bills for them to become law, said the bill could not come into force because the European Commission was not properly notified under a process aimed at giving it and member states time to react.
France to ban dozens of glyphosate weedkillers amid health risk debate [Reuters] ANSES said it would complete its review of glyphosate products by the end of next year, and that only products that met EU criteria and which did not have adequate alternatives would be allowed to be sold in France. Bayer’s home country Germany will ban the substance from the end of 2023.
	4.9 DÉP., DIAG. & PRONO. - SEIN
New test predicts chance of living more than a year on targeted breast cancer treatment [Institute of Cancer Research] Researchers found that testing for cyclin E1 could predict the chances of a year or more of successful treatment with a drug called palbociclib – a drug hailed by doctors as the biggest advance in breast cancer treatment for 20 years.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Researchers Create a Potential Therapy for Deadly Breast Cancer That Has Few Treatment Options [Mount Sinai] The therapy is known is MS1943. In a cancer cell line and mouse models, it degraded a protein called EZH2 that drives the growth of triple-negative breast cancer.
	5.12.11 IMMUNOTHÉRAPIES - PRÉ-CLINIQUE
PAK4 Inhibition Increases Anti-PD-1 Response in Mouse Models Prompting Phase I Trial [Genome Web] Researchers from the University of California at Los Angeles, Karyopharm Therapeutics, and elsewhere did RNA sequencing on dozens of individuals with melanoma, searching for gene expression features that coincided with enhanced or diminished immune T cell infiltration of tumors in samples collected before and during PD-1 blockage treatment.
UCLA study shows inhibition of gene helps overcome resistance to immunotherapy [UCLA] The UCLA study, published today in the inaugural issue of the new scientific journal Nature Cancer, showed that genetic and pharmacological inhibition of the oncogene PAK4 overcomes resistance to anti-PD-1 therapy in preclinical models.
Cancer immunotherapy gets assist from micro-scale engineering [Fred Hutch] In a study published Dec. 9 in the journal Nature Biomedical Engineering, Stephan showed that loading genetically engineered immune cells onto a metal micromesh-based tumor stent can keep tumors from growing into and blocking the stent in a preclinical model of pancreatic cancer.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Bristol-Myers is making a bee-line to the FDA with positive liso-cel data — but is it too late in the CAR-T game? [EndPoints] Liso-cel is the long delayed followup to the disastrous JCAR015, which killed a number of patients. Their setback threw them years off schedule. And rivals are advancing off-the-shelf alternatives or other new approaches that could knock the pioneers completely out of the game.
	5.12.6 IMMUNOTHÉRAPIES - AMM
FDA Approves Atezolizumab With Nab-paclitaxel and Carboplatin for Metastatic Non-squamous NSCLC Without EGFR/ALK Aberrations [ESMO] Efficacy was evaluated in IMpower130 (NCT02367781), a multicentre, randomised (2:1), open-label trial in patients with stage IV non-squamous NSCLC who had received no prior chemotherapy for metastatic disease, but could have received prior EGFR or ALK kinase inhibitor, if appropriate.
	5.2 PHARMA
Sanofi CEO Hudson lays out new R&D focus -- chopping diabetes, cardio and slashing $2B-plus costs in surgical dissection [EndPoints] Hudson’s also laying the trail with new tidbits aimed at leading the industry into tomorrow’s presentation — which will almost certainly focus entirely on the company’s plans to hammer out its destiny through the pipeline. And look for cancer drugs to be on top of that conversation.
Sanofi ends research in diabetes, narrows units to spur profit [Reuters] The firm is bulking up elsewhere, as in the lucrative field of cancer drugs.
	5.2.1 PHARMA - PARTENARIATS
Adaptive and AbbVie Partner Across Multiple Myeloma Trials to Measure Minimal Residual Disease Using the clonoSEQ® Assay [Adaptive Biotechnologies] Adaptive Biotechnologies Corporation today announced a multi-year, global collaboration agreement with AbbVie to utilize Adaptive’s next-generation sequencing (NGS)-based clonoSEQ® Assay to assess minimal residual disease (MRD) status in response to venetoclax across multiple myeloma (MM) clinical trials.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
Merck's ArQule buy showcases pharma appetite for targeted cancer drugs [Biopharma Dive] Kinase inhibitors have been a hot area for biopharma dealmaking, with BTK-targeting drugs especially attractive. At least four acquisitions over the past decade revolved around BTK inhibitors.
Eying Cancer Combos, Sanofi to Splash Out $2.5B on San Diego’s Synthorx [Xconomy] In a letter to Sanofi employees, Reed said the company envisions opportunities to combine the Synthorx tech with nanobodies, a technology developed by Belgian company Ablynx for which Sanofi paid €3.9 billion ($4.3 billion) last year, in addition to other immunotherapies.
Sanofi CEO offers clues of tomorrow's vision reveal with cancer biotech buy [Fierce Pharma] In pulling off a biotech buyout now, Hudson extends former CEO Olivier Brandicourt's deal series, albeit in cancer rather than Brandicourt's rare disease focus.
Merck inks $2.7B ArQule deal, teeing up cancer race with Lilly [Fierce Biotech] The readout came one day after Lilly shared encouraging data on its BTK inhibitor at ASH, setting up a potential scrap that at this early stage is too close to call.
Sanofi buys Synthorx for $2.5B in prelude to Hudson's strategy rollout [Biopharma Dive] The deal is an aggressive and early bet on cancer research by Paul Hudson, who started as Sanofi's CEO in September. Little clinical data supports Synthorx's platform, and the French pharma is paying $68 per share, representing a steep 172% premium.
Merck Makes a Big Blood Cancer Bet With $2.7B Deal for ArQule [Xconomy] Lead ArQule drug candidate ARQ 531 is a small molecule currently in Phase 2 dose expansion study in B-cell malignancies, or blood cancers, that have not responded to other treatments. The drug targets Bruton’s tyrosine kinase (BTK), a protein that plays a key role in the expansion of chronic lymphocytic leukemia (CLL), the most common form of leukemia.
New Sanofi CEO Hudson adds next-gen cancer drug tech to the R&D quest, buying Synthorx for $2.5B [EndPoints] With THOR-707, Synthorx is pegylating recombinant human IL-2 at one specific site, by creating a hook with its synthetic amino acid X-Y, so as to avoid binding with the high affinity IL-2 receptor α chain.
Merck and Sanofi buy smaller cancer drug firms at big premiums, fueling investor excitement [STAT] The drug giants Merck and Sanofi each said they would acquire a smaller drug maker for more than $2 billion Monday — in each case, more than double the smaller company’s market capitalization — cheering investors about large companies’ appetite to execute buyouts in the biotechnology sector.
Merck to Acquire ArQule, Advancing Leadership in Oncology [Merck] Acquisition Further Diversifies Merck’s Oncology Pipeline with Expansion into Targeted Therapies That Treat Hematological Malignancies.
Here’s why Merck is paying $2.7B today to grab ArQule and its next-gen BTK drug, lining up Eli Lilly rivalry [EndPoints] ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.
	5.8.3 ASH - DIVERS
ASH Study: Germline Testing Identifies Cancer Risk Mutations, VUS in Older AML Patients [Genome Web] The study also found a particularly high prevalence of variants of unknown significance, illustrating the need for more efforts to definitively classify the pathogenicity of variants that can be important for treating AML patients.
Gimme shelter: CRISPR hides healthy cells from leukemia drug [Fred Hutch] In mouse study, gene-edited cells stay safe as immunotherapy attacks cancer.
	5.8.4 ASH - CAR-T
As CAR-T presses ahead in multiple myeloma, alternative approaches gain supporters [Biopharma Dive] Other companies are betting that the share of patients who choose the off-the-shelf therapies will be large enough to justify spending money on their research and development. Among those are Regeneron Pharmaceuticals, Amgen, GlaxoSmithKline and Pfizer.
Novartis Kymriah® demonstrates consistent efficacy and safety outcomes in US patients when used in real-world setting [Novartis] These analyses are from a readout of a 15-year post-marketing study that add to and complement the rigor of the Kymriah pivotal trials with evidence of the Kymriah real-world experience in expanded groups of patients.
Bridging Therapy Not Recommended for All CAR T Patients [Moffitt Cancer Center] Jain and his collaborators looked at the consortium data to determine if administering a bridging therapy – radiation, chemotherapy, steroids or targeted therapy – could help patients in declining health who were waiting for their CAR T treatment to be scheduled.
	5.8.5 ASH - MYÉLOME MULTIPLE
ASH: J&J's anti-BCMA CAR-T clears multiple myeloma in 69% of patients in phase 1 [Fierce Biotech] The trial was small and focused on gauging safety and picking a dose for phase 2, but the efficacy results are encouraging, especially in a patient group that has “essentially run out of treatment options.”
ASH: Amgen's BiTE stalls multiple myeloma relapse in mice in combo with BMS' Revlimid [Fierce Biotech] Unlike CAR-T treatments, which are made from individual patients’ cells, BiTEs are off the shelf, so they can be prescribed and administered with no delay. The technology has already produced one winner for Amgen—Blinctyo to treat acute lymphoblastic leukemia.
ASH: J&J's Darzalex cuts death risk by 40% in new myeloma patients [Fierce Pharma] At the 42-month mark of the trial—dubbed Alcyone—75% of Darzalex patients were still alive, versus 62% of those receiving the regimen without the J&J drug.
DARZALEX® (Daratumumab) Shows Overall Survival Benefit and Continued Improvement in Progression-Free Survival in Patients with Newly Diagnosed Multiple Myeloma Who Are Ineligible for Transplant [Johnson & Johnson] DARZALEX® is the only CD38-directed antibody to show an overall survival benefit in multiple myeloma.
Bluebird bio, Bristol-Myers' multiple myeloma therapy shows promise in early study [Reuters] With bb21217, the companies are looking to prolong the persistence of CAR-T cells in the body, which could translate into more durable clinical responses following treatment.
Game on: Regeneron's BCMA bispecific makes clinical data debut, kicking off multiple myeloma matchup with Bristol-Myers [EndPoints] With bispecifics the general idea is to bridge T cells and tumors cells, thereby inducing the killing of cancer. REGN5458, in particular, binds to the CD3 receptor on the immune cells and BCMA on multiple myeloma cells.
bluebird bio and Bristol-Myers Squibb Present Updated Data from Ongoing Phase 1 Study of BCMA-Targeted CAR T Cell Therapy bb21217 in Relapsed/Refractory Multiple Myeloma at 61st ASH Annual Meeting and Exposition [BMS] CAR T persistence observed in 8/10 evaluable responders at Month 6 and 2/2 evaluable responders at Month 18.
	5.8.6 ASH - LEUCÉMIES
ArQule Announces Final Phase 1 Clinical Data for Its Reversible BTK Inhibitor, ARQ 531, at the American Society of Hematology 2019 Annual Meeting [ArQule] Eight of nine evaluable CLL patients initially dosed at ≥65 mg experienced a Partial Response (PR).
Combination therapy more effective than chemotherapy alone for many newly diagnosed leukemia patients [MD Anderson Cancer Center] Enasidenib plus azacitidine significantly improves complete remission and overall response for patients with acute myeloid leukemia tied to IDH2 mutations.
Leukemia Combo Toxic for Old, Frail Patients [SWOG] About 32 percent of older, sicker patients enrolled on a leukemia clinical trial experienced serious side effects from a treatment that combined a chemotherapy and an immunotherapy drug, leading investigators to pause the trial and the U.S. Food and Drug Administration to eventually pull the combination from the current study.
	5.8.7 ASH - LYMPHOMES
Treatment with PD-1 inhibitor prior to stem cell transplant is safe, effective for patients with classic Hodgkin lymphoma, study finds [Dana-Farber Cancer Institute] Post-transplant treatment with cyclophosphamide reduces rates of acute GVHD and relapse.
Kite Presents Positive Results From Pivotal ZUMA-2 Trial in Relapsed or Refractory Mantle Cell Lymphoma [Kite] Findings Support Regulatory Filings for Kite’s Second CAR T Cell Therapy.
Seattle Genetics and Takeda Announce Additional Analyses of ADCETRIS® (Brentuximab Vedotin) ECHELON-1 and ECHELON-2 Phase 3 Clinical Trials at the 2019 ASH Annual Meeting [Takeda] Four-Year Data Continue to Show Superior Progression-Free Survival of ADCETRIS in Combination with AVD when Compared to ABVD in Frontline Advanced Hodgkin Lymphoma with 31 Percent Reduction in the Risk of Progression or Death.
CAR T-cell therapy effective for relapsed mantle cell lymphoma patients [MD Anderson Cancer Center] The multi-center, Phase II study reported that 93% of patients responded to the CAR T-cell therapy, with 67% achieving a complete response. Forty-three percent of the first 28 patients treated are still in remission over two years later.
	6.5 MÉDECINES ALTERNATIVES/COMPLÉMENTAIRES
Spinning a negative acupuncture study: Same as it ever was [Science-Based Medicine] Investigators at M.D. Anderson Cancer Center reported the results of a trial of acupuncture for xerostomia (dry mouth) secondary to radiation therapy for head and neck cancers. It was a negative trial, but investigators still tried to spin it as positive, but with a twist. There was a large difference between results found at M.D. Anderson and the second site in China. What could be going on?