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NEWS
CANCER RESEARCH INSTITUTE
06 Apr 2016

Ludwig Cancer Research and the Cancer Research Institute (CRI) have launched a Phase 1/2 clinical trial of combination immunotherapy for advanced ovarian cancer. The international, multicenter trial is led by George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne and Brad Monk, director of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center. […]

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Ludwig Cancer Research and the Cancer Research Institute (CRI) have launched a Phase 1/2 clinical trial of combination immunotherapy for advanced ovarian cancer. The international, multicenter trial is led by George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne and Brad Monk, director of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center. The study is being conducted through the CVC Trials Network, which is jointly managed by Ludwig and CRI, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, and the biopharmaceutical company VentiRx Pharmaceuticals Inc.

“Ludwig has long supported the design and evaluation of new therapeutic strategies to improve the treatment options available to cancer patients,” said Jonathan Skipper, Ludwig’s executive vice president of Technology Development. “Employing immunotherapies in combination holds great promise in that endeavor. We are proud to be a part of this effort to bring investigational drugs being developed by different commercial partners to a single clinical trial and improve the standard of care for recurrent ovarian cancer, a disease for which patients today have few treatment options.”

The open-label trial is evaluating the combination of MedImmune’s investigational antibody cancer drug durvalumab, a PD-L1 inhibitor, and VentiRx’s investigational TLR8 agonist motolimod added to chemotherapy in locally advanced or recurrent ovarian cancers that have become resistant to platinum chemotherapy. Both of the investigational drugs have been found in other studies to have acceptable safety profiles when used alone.

The researchers expect that motolimod’s activation of TLR8 will create conditions within tumors that are optimal to enhancing the effects of durvalumab. Further, when given with chemotherapy, motolimod could boost immune responses against cancer cells that are not engaged by durvalumab by helping the immune system “see” cancer antigens. Since the two immunotherapies work in distinct ways, they could have additive effects, inducing more potent and durable anti-tumor immune responses.

“This study is a good example of what’s possible when researchers have access to new therapies and are permitted to test hypotheses supported by the most recent science,” said Ludwig Lausanne director George Coukos. “We are hopeful that the combined therapies we are testing in this trial will be of great benefit to ovarian cancer and other cancer patients.”

Patients enrolled in the trial will be treated with the chemotherapeutic drug pegylated liposomal doxorubicin (PLD), which is the current standard of care for ovarian cancer after the failure of platinum therapy. They will also receive durvalumab and motolimod, with the Phase 1 and 2 portions of the trial running successively. The primary objective of the Phase 1 cohort of the study is to evaluate the safety and optimal dosage of the combination. The Phase 2 cohort of the trial will measure the efficacy of the treatment by evaluating the number of patients whose tumors have not progressed at six months.

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 expression enables tumours to evade detection from the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient’s immune system and attack the cancer. Durvalumab is being investigated in an extensive clinical trial program, as monotherapy or in combination with tremelimumab, in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers.

Motolimod binds and activates Toll-like receptor 8 (TLR8), which is found in a variety of immune cells and serves as a key initiator of the innate immune response. Notably, it is expressed by myeloid dendritic cells, which help direct and boost T cell responses against infectious agents and cancers. Motolimod has been shown to be safe when combined with PLD in a previous study on ovarian cancer, with evidence of clinical benefit. The motolimod-PLD combination is currently under evaluation in a large, randomized, placebo-controlled phase 2 clinical study in patients with ovarian cancer.

“This clinical trial is part of a larger clinical research program supported by Ludwig and CRI to speed the evaluation of novel cancer immunotherapies, alone or in combination with other cancer drugs,” said Adam Kolom, managing director of CRI’s Clinical Accelerator, which funds the trials. “All of the studies have, as additional objectives, the collection of genetic and immunologic data derived from clinical samples that are obtained from patients. Such information will provide clues to the impact of the evaluated therapies and suggest refined or new strategies for treating cancer.”

NEWS
NEW YORK TIMES
18 Feb 2015

New York Times The Metropolitan Opera said on Wednesday that it would redouble its efforts to attract new audiences to the opera next season with six new productions, a star-filled roster and new initiatives, including one that will offer half-priced tickets to children during the holidays and another to court young professionals with later curtain […]

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New York Times

The Metropolitan Opera said on Wednesday that it would redouble its efforts to attract new audiences to the opera next season with six new productions, a star-filled roster and new initiatives, including one that will offer half-priced tickets to children during the holidays and another to court young professionals with later curtain times, discounts and social events.

“The future of opera relies upon bringing new audiences in, as we all know,” Peter Gelb, the Met’s general manager, said in an interview. “Ultimately, no matter what the economics are, how daunting they are, or how successful we are in fund-raising, at the end of the day it’s all about having an audience.”

While the initiatives are aimed at newcomers, the season should offer plenty to interest regular operagoers. Nina Stemme, the acclaimed Swedish dramatic soprano whose New York appearances have been few and far between, will return to the Met next season to sing the title roles in a new production of Strauss’s “Elektra” and a revival of Puccini’s “Turandot.”

The star tenor Jonas Kaufmann and the soprano Kristine Opolais will perform in a new production of Puccini’s “Manon Lescaut” directed by Richard Eyre. James Levine, the Met’s music director, will conduct a new production of Berg’s “Lulu,” which he described in an interview as “an inspired work, from beginning to end.” The production will be staged by the South African artist William Kentridge, who did the Met’s innovative production of “The Nose.”

And, reprising a feat that Beverly Sills was famous for, Sondra Radvanovsky will sing all three queens in Donizetti’s so-called Tudor trilogy next season. She will sing the title roles in revivals of “Anna Bolena” and “Maria Stuarda” and then, when the Met brings “Roberto Devereux” to its stage for the first time in a new David McVicar production, she will perform the role of Elizabeth I, who, unlike the other two queens, manages to keep her head.

Two more new productions will round out the season: The Met will stage its first production of Bizet’s “Les Pêcheurs de Perles” (The Pearl Fishers) since 1916. It will be directed by Penny Woolcock; conducted by Gianandrea Noseda; and star Diana Damrau, Matthew Polenzani and Mariusz Kwiecien. (Mr. Gelb noted that the last tenor to sing the role Mr. Polenzani is singing was Enrico Caruso. “Hopefully there’s been enough time in between,” he said.)

And the Met will open its season with a new production of Verdi’s “Otello” directed by Bartlett Sher; conducted by Yannick Nézet-Séguin; and starring Sonya Yoncheva, who had several star-making turns this season, as Desdemona, and Aleksandrs Antonenko in the title role.

Some of the big moments of the season will be in revivals: Anna Netrebko, who made a splash this year in Verdi’s “Macbeth,” will sing Leonora in Verdi’s “Il Trovatore” for the first time at the Met. She will make her New York recital debut with a solo concert on Feb. 28, 2016.

 

The Met, which has been struggling financially and at the box office in recent seasons — it ran a $22 million deficit last year — announced a series of steps to court new audiences.

Children under 18 will be able to receive half-price tickets in any section of the house between Thanksgiving and New Year’s Eve, when purchased with a full-priced ticket.

A new program called “Fridays Under Forty” will offer tickets on selected Friday nights to people under 40 for $60 and $100 and move the curtain time back to 8 p.m., from its usual 7:30 p.m., to accommodate young professionals who work long hours.

And the Met plans to build on its popular holiday presentations aimed at families by adding one for grown-ups. So in addition to reviving an abridged, English-language revival of Rossini’s “The Barber of Seville” aimed at children, starring Isabel Leonard as Rosina, the Met will add one for adults: a streamlined revival of Johann Strauss’s “Die Fledermaus,” conducted, for his first time, by Mr. Levine.

The average ticket price will increase by 1 percent to $160, the Met said. Tickets will range in price from $25 to $480, with 36 percent of the roughly 900,000 tickets available next season for under $100, and more than half available for under $150.

Mr. Levine is to conduct five operas next season. In addition to “Lulu” and “Die Fledermaus,” he will conduct Verdi’s “Simon Boccanegra” with Plácido Domingo in the title role; Mozart’s “Die Entführung aus dem Serail”; and Wagner’s “Tannhäuser” starring Johan Botha, Peter Mattei, Eva-Maria Westbroek and Michelle DeYoung.

There are no contemporary works next season, but the Met, which has made a greater priority of new works in recent years, announced that it had commissioned a new opera by Nico Muhly, the composer of “Two Boys.” Mr. Muhly will write “Marnie,” based on the 1961 Winston Graham novel that was adapted for the screen by Alfred Hitchcock, and which is scheduled to come to the Met’s stage, in a production directed by Michael Mayer, in the 2019-20 season.

“It does everything that you want an opera to do, really,” Mr. Muhly said of the book. “It’s really, really dark.”