BOSTON (AP) — Slain Boston Marathon bombing suspect Tamerlan Tsarnaev was named as a participant in an earlier triple homicide by a man who was subsequently shot to death while being questioned by authorities, according to a filing made by federal prosecutors in the case against his brother, surviving bombing suspect Dzhokhar Tsarnaev.
According to the filing made Monday, Ibragim Todashev told investigators Tamerlan Tsarnaev participated in a triple slaying in Waltham on Sept. 11, 2011.
In that case, three men were found in an apartment with their necks slit and their bodies reportedly covered with marijuana. One of the victims was a boxer and friend of Tamerlan Tsarnaev.
Todashev, a 27-year-old mixed martial arts fighter, was fatally shot at his Orlando home during a meeting with an FBI agent and two Massachusetts state troopers in May, authorities said. He had turned violent while being question, according to authorities.
The filing is prosecutors' attempt to block Dzhokhar Tsarnaev from getting certain information from authorities, including investigative documents associated with the Waltham slayings.
"The government has already disclosed to Tsarnaev that, according to Todashev, Tamerlan Tsarnaev participated in the Waltham triple homicide," prosecutors wrote.
According to prosecutors, the ongoing investigation into the 2011 slayings is reason not to allow Dzhokhar Tsarnaev access to the documents he's seeking.
"Any benefit to Tsarnaev of knowing more about the precise 'nature and extent' of his brother's involvement does not outweigh the potential harm of exposing details of an ongoing investigation into an extremely serious crime, especially at this stage of the proceeding," prosecutors wrote.
Prosecutors also said Dzhokhar Tsarnaev is not entitled to the information because his brother's criminal history will be relevant, if at all, only at a possible future sentencing hearing.
A phone message left for a spokeswoman for the U.S. Attorney's Office was not immediately returned Tuesday night. A message left for Dzhokhar Tsarnaev's federal public defender was also not immediately returned.
Authorities allege that Dzhokhar Tsarnaev, 20, and 26-year-old Tamerlan Tsarnaev, ethnic Chechens from Russia, planned and carried out the twin bombings near the finish of the marathon on April 15. Three people were killed and more than 260 were injured.
Dzhokhar Tsarnaev faces 30 federal charges, including using a weapon of mass destruction and 16 other charges that carry the possibility of the death penalty.
Tamerlan Tsarnaev died in a gunbattle with police as authorities closed in on the brothers several days after the bombings.
WASHINGTON (AP) — The United States on Tuesday defended drone strikes targeting al-Qaida operatives and others it deems enemies, rejecting reports by two human-rights groups questioning the legality of strikes they asserted have killed or wounded scores of civilians in Yemen and Pakistan.
Human Rights Watch alleged that 82 people, at least 57 of them civilians, were killed by the unmanned aircraft and other aerial strikes in Yemen between September 2012 and June 2013 and called such strikes unlawful or indiscriminate. Amnesty International called on the U.S. to investigate reports in Pakistan of civilian casualties, among them a 68-year-old grandmother hit while farming with her grandchildren.
The New York-based Human Rights Watch said such strikes are unlawful or indiscriminate. Amnesty, based in London, said it is concerned that the attacks outlined in the report and others may have resulted in unlawful killings that constitute extrajudicial executions or war crimes.
President Barack Obama's chief spokesman, Jay Carney, said the U.S. "would strongly disagree" with any claims that the U.S. had acted improperly, arguing that American actions follow all applicable law.
Repeating Obama's defense of the drone policy earlier in the year, Carney said there must be "near-certainty" of no civilian casualties before the U.S. proceeds with a drone strike. He said they're not used when targets can instead be captured.
"U.S. counterterrorism operations are precise, they are lawful and they are effective," Carney said.
Other methods of going after targets would result in even more civilian casualties "and ultimately empower those who thrive on violent conflict," Carney said. He added that there's a wide gap between U.S. assessment of drone-related civilian casualties and what some non-governmental groups have determined.
Amnesty said the U.S. is so secretive about the drone program that there is no way to tell what steps it takes to prevent civilian casualties. They say it has "failed to commit to conduct investigations" into alleged deaths that have already occurred, and it called on the U.S. to comply with its obligations under international law by investigating the killings documented in the report and providing victims with "full reparation."
In its report about strikes in Yemen, Human Rights Watch charged that each of six cases examined through interviews with Yemeni officials, witnesses and survivors, drone or other aerial strikes were carried out despite the presence of civilians, in contravention of the laws of war.
The strikes are part of a joint U.S.-Yemeni campaign against al-Qaida in the Arabian Peninsula, called the most dangerous al-Qaida branch. It's blamed for a number of unsuccessful bomb plots aimed at Americans, including a failed plan to down a U.S.-bound airliner with explosive hidden in the bomber's underwear and a second plot to send mail bombs on planes to the U.S. hidden in the toner cartridges of computer printers.
The Yemeni Embassy in Washington said in a statement to The Associated Press that Yemen has adopted strict measures to avoid targeting militants in civilian areas, and only uses drones "in remote areas to target militants that are out of the reach of security personnel" who present an immediate danger because they "are planning to carry out terror attacks inside the capitals of governorates."
Among the six strikes detailed by Human Rights Watch is an attack in Sarar, in central Yemen on Sept. 2, 2012, in which two warplanes or drones attacked a minibus, killing a pregnant woman, three children and eight other people. The report said the apparent target, tribal leader Abd al-Raouf al-Dahab, was not in the vehicle. The Yemeni families were only compensated for the deaths after Human Rights Watch brought the case to the Yemeni government's attention, the report said.
The researchers also examined the U.S. cruise missile strike in al-Majalah in southern Abyan province on Dec. 17, 2009. The report said the Yemeni government described the attack as a Yemeni airstrike that killed 34 at a training camp, but a later Yemeni government inquiry found the strike actually killed 14 suspected AQAP fighters, but also at least 41 local civilians living in a Bedouin camp, including nine women and 21 children.
The Yemeni president acknowledged the 2009 strike in an interview last year. The Yemeni Embassy statement Tuesday said the surviving families had been compensated. The statement said the use of drones was under review as part of the country's ongoing national dialogue between the president and Yemeni tribal factions.
In Pakistan, the U.S. considers its drone program to be a key weapon against insurgent groups that it says stages cross-border forays into neighboring Afghanistan. But the belief, widespread in Pakistan, that the strikes kill large numbers of civilians sparks resentment and complicates the two countries' ability to coordinate efforts against militants based in the country, including al-Qaida.
The U.S. drone policy sets a dangerous precedent "that other states may seek to exploit to avoid responsibility for their own unlawful killings," Amnesty said.
Amnesty's report said that the grandchildren of the woman killed told the group that missile fire struck on Oct. 24, 2012, as she was collecting vegetables in a family field in the North Waziristan tribal area, a major militant sanctuary near the Afghan border. Three of the grandchildren were wounded, as were several others who were nearby, the victims said.
An even deadlier incident noted by the Amnesty report occurred in North Waziristan on July 6, 2012. Witnesses said a volley of missiles hit a tent where a group of men had gathered for an evening meal after work, and then a second struck those who came to help the wounded, one of a number of attacks that have hit rescuers, the rights group said.
Witnesses and relatives said that 18 male laborers with no links to militant groups died, according to Amnesty. Pakistani intelligence officials at the time identified the dead as suspected militants.
"We cannot find any justification for these killings. There are genuine threats to the USA and its allies in the region, and drone strikes may be lawful in some circumstances," said Mustafa Qadri, Amnesty International's Pakistan researcher. "But it is hard to believe that a group of laborers, or an elderly woman surrounded by her grandchildren, were endangering anyone at all, let alone posing an imminent threat to the United States."
Pakistani officials regularly denounce the attacks in public as a violation of the country's sovereignty, but senior members of the government and the military are known to have supported the strikes in the past.
___
Associated Press writers Sebastian Abbot and Asif Shahzad in Islamabad and Josh Lederman in Washington contributed to this report.
Follow Kimberly Dozier on Twitter at http://twitter.com/kimberlydozier
Gearing up for another day in New Orleans, Ryan Reynolds continued filming for his new film "Selfless" on Tuesday (October 22).
The "R.I.P.D." star wore a dark blue blazer and dark slacks as he hopped out of a limo onto the set.
Recently, Reynolds was apparently forced to go shirtless while on a flight with his wife Blake Lively.
According to RadarOnline, another passenger on the flight threw up all over his sweater. "She had clearly had too much to drink, causing her to be sick," a source told the tabloid.
The insider also mentioned that Ryan simply took off the shirt and acted as though nothing was wrong while the flight attendants assisted him.
For the whys and whos of Detroit's Sense of Place in rock history, World Cafe host David Dye talks with Motor City music icon Wayne Kramer. In the 1960s, Kramer co-founded the MC5, the loud, passionate, radical rock band that served as the foundation of much of the Detroit rock that came later.
In this session, Kramer provides insight into how the economic woes of the city — and the consequent rise in crime — affected the music scene. He also describes the scene at the Grande Ballroom when shouts of "Kick out the jams!" led to the MC5's best-known song.
The rock veteran also takes some time to discuss his charity Jail Guitar Doors USA, which he founded with musician Billy Bragg to provide instruments for incarcerated musicians.
A few weeks ago, a tiny gallery in London was transformed into a scene straight out of the 19th century. Amid piles of sand, a worker donned a silver apron and safety helmet and poured molten hot steel down a track to create long slabs of metal. The man in the apron was Raphael Hefti—not an industrial worker, but an artist.
Investigational PARP inhibitor promising in BRCA-related cancers
PUBLIC RELEASE DATE:
22-Oct-2013
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Contact: Lauren Riley lauren.riley@aacr.org 215-446-7155 American Association for Cancer Research
BOSTON An investigational new PARP inhibitor, BMN 673, is showing early responses in patients with heavily pretreated, advanced, BRCA-related cancers of the breast and ovary, according to phase I clinical trial results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.
When there is damage to DNA in human cells, two proteins, PARP 1 and 2, recruit proteins that can repair the damage associated with loss of BRCA proteins. Mutations in BRCA genes often result in inefficient repair of damaged DNA, which increases the risk for developing certain cancers, including cancers of the breast and ovary. Inhibiting PARP, therefore, prevents the repair of damaged DNA, leading to cell death. While some PARP inhibitors have been tested in various settings, none are approved to date.
"BMN 673 is the most potent PARP inhibitor in clinical development and has optimized pharmaceutical properties: it is well absorbed orally, has substantial single-agent antitumor activity, and has a long half-life allowing once-daily dosing," said Zev A. Wainberg, M.D., assistant professor of medicine at the Jonsson Comprehensive Cancer Center of the University of California Los Angeles School of Medicine. "The clinical data to date are promising and compare favorably with results from clinical trials with other PARP inhibitors. We observed high objective and clinical benefit response rates in BRCA-related breast and ovarian cancers at low, oral, once-daily doses.
"Based on this phase I study, we feel there's a good chance that patients with BRCA-related cancers who meet the study eligibility criteria will have disease control for a meaningful period of time with relatively few side effects. However, randomized trials are necessary to demonstrate whether this will translate into improvements in progression-free and overall survival relative to currently available therapies," said Wainberg.
He and colleagues conducted a phase I trial to evaluate the safety and efficacy of BMN 673 in a two-stage dose escalation/expansion study. So far, they have recruited 39 and 41 patients to the escalation phase and expansion phase, respectively. Patients were 18-82 years old, and they had undergone one to 13 prior therapies.
Fifty participants18 with breast cancer, 28 with ovarian cancer, three with pancreatic cancer, and one with prostate cancerhad BRCA mutations in their tumors. Wainberg reported that to date, among the patients with BRCA mutations in their tumors, 44 percent of those with ovarian cancer and 44 percent with breast cancer had an objective response. Overall, 82 percent of the ovarian cancer patients and 72 percent of the breast cancer patients had clinical benefit (measured by imaging data and/or CA 125 levels for ovarian cancers and by imaging data for breast cancers).
In patients being treated at the 1 mg dose recommended for future trials, 50 percent of the breast cancer patients with BRCA mutations had an objective response and 86 percent had clinical benefit. Of the three patients with pancreatic cancer, two have had stable disease.
Fewer than 20 percent of the patients had grade 3 adverse events including fatigue, anemia, neutropenia, and thrombocytopenia, and one patient had a grade 4 toxicity.
Given the high objective and clinical benefit response rates in breast cancer patients, the investigators have recently initiated a phase 3 trial in metastatic breast cancer with BRCA mutations, according to Wainberg.
Among those with BRCA-unrelated cancers recruited to the phase 1 trial, one of the seven currently evaluable patients with small-cell lung cancer (SCLC) has responded, according to Wainberg. This patient, whose tumor metastasized extensively, has an ongoing partial response, he explained. "A solid partial response in a patient with SCLC provides some optimism about finding indications other than BRCA-related tumors that will benefit from treatment with BMN 673," he said.
###
This study was sponsored by BioMarin Pharmaceutical. Wainberg has no conflicts of interest to declare.
The 2013 International Conference on Molecular Targets and Cancer Therapeutics is being co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC).
This research will be presented at a press conference entitled "Guiding Treatment for BRAF- and BRCA-related Cancers" during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on Monday, Oct. 22 at 9 a.m. ET in room 202 of the Hynes Convention Center in Boston, Mass. Reporters who cannot attend in person may call in using the following numbers:
U.S./Canada (toll-free): 800-446-2782
International (toll): 847-413-3235
To interview Zev Wainberg, contact Shaun Mason at smason@mednet.ucla.edu or 310-206-2805. For other inquiries, contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109.
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org. Follow the AACR on Twitter: @AACR. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.
About the National Cancer Institute
The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
About the European Organisation for Research and Treatment of Cancer
The European Organisation for the Research and Treatment of Cancer (EORTC) brings together European cancer clinical research experts from all disciplines for trans-national collaboration. Both multinational and multidisciplinary, the EORTC Network comprises more than 2,500 collaborators from all disciplines involved in cancer treatment and research in more than 300 hospitals in over 30 countries. Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices.
EORTC Headquarters, a unique pan European clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run. http://www.eortc.org
Abstract Number: C295
Presenter: Zev A. Wainberg, M.D.
Title: Update on first-in-man trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors
Authors: Zev A. Wainberg1, Johann S. de Bono2, Lida Mina3, Jasgit Sachdev4, Lauren Averett Byers5, Rashmi Chugh6, Charlie Zhang7, Joshua W. Henshaw7, Andrew Dorr7, John Glaspy1, Ramesh Ramanathan4. 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; 3Indiana University, Indianapolis, IN; 4Virginia G. Piper Cancer Center at Scottsdale Healthcare/Tgen, Scottsdale, AZ; 5University of Texas MD Anderson Cancer Center, Houston, TX; 6University of Michigan, Ann Arbor, MI; 7BioMarin Pharmaceutical, Novato, CA
Background: BMN 673 is the most potent and specific inhibitor of PARP1/2 in clinical development (IC50Methods: Pharmacokinetics (PK), pharmacodynamics (PD), safety and anti-tumor activity of BMN 673 were evaluated in a 2-stage escalation/expansion study. Expansion included cohorts of pts with BRCA-related cancers, small cell lung cancer (SCLC) and Ewing sarcoma (ES).
Results: (As of July 29, 2013) In escalation, 39 pts were enrolled in 9 cohorts from 25 to 1100 g/d with 1000 g/d being the MTD related to dose-limiting hematologic toxicity. 38 pts have been enrolled in expansion including 25 patients with BRCA related cancers. For all 77 (63F/14M) pts, median age (range) is 52 (18-81), PS, 0 (0-1) and # of prior therapies 4 (1-13). Eight ES, 7 SCLC and 48 patients with deleterious BRCA mutations and breast (n=18), ovarian (n=28) or pancreatic (n=2) cancer were enrolled. BMN 673 demonstrated good oral bioavailability and a long half-life supporting daily dosing (ASCO 2013 Abstract 2580). One related grade 4 toxicity (thrombocytopenia) occurred. Related grade 3 adverse events have included fatigue, anemia, neutropenia and thrombocytopenia, all in fewer than 15% of patients. Dose-related inhibition of PARP activity in PBMC's was observed. Response, reduction in neutrophils and platelets and the need for blood transfusions and dose reductions appear to correlate with BMN 673 exposure.
^3 breast cancer responses are not yet confirmed; *CBR: clinical benefit response; **CA19-9 normalized in 1 patient
Overall, the objective response (including CA-125) and clinical benefit response rates are for all BRCA patients are 60.4% and 81%, respectively.
Treatment is ongoing in 5 of 7 SCLC patients and 2 of 8 ES patients with no objective responses observed yet.
Conclusions: BMN 673 is well tolerated with high objective and clinical benefit response rates in heavily pre-treated ovarian and breast cancer pts with deleterious germline BRCA mutations. A phase 3 trial in metastatic breast cancer is underway.
Clinicaltrial.gov ID: NCT01286987
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Investigational PARP inhibitor promising in BRCA-related cancers
PUBLIC RELEASE DATE:
22-Oct-2013
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]
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Contact: Lauren Riley lauren.riley@aacr.org 215-446-7155 American Association for Cancer Research
BOSTON An investigational new PARP inhibitor, BMN 673, is showing early responses in patients with heavily pretreated, advanced, BRCA-related cancers of the breast and ovary, according to phase I clinical trial results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.
When there is damage to DNA in human cells, two proteins, PARP 1 and 2, recruit proteins that can repair the damage associated with loss of BRCA proteins. Mutations in BRCA genes often result in inefficient repair of damaged DNA, which increases the risk for developing certain cancers, including cancers of the breast and ovary. Inhibiting PARP, therefore, prevents the repair of damaged DNA, leading to cell death. While some PARP inhibitors have been tested in various settings, none are approved to date.
"BMN 673 is the most potent PARP inhibitor in clinical development and has optimized pharmaceutical properties: it is well absorbed orally, has substantial single-agent antitumor activity, and has a long half-life allowing once-daily dosing," said Zev A. Wainberg, M.D., assistant professor of medicine at the Jonsson Comprehensive Cancer Center of the University of California Los Angeles School of Medicine. "The clinical data to date are promising and compare favorably with results from clinical trials with other PARP inhibitors. We observed high objective and clinical benefit response rates in BRCA-related breast and ovarian cancers at low, oral, once-daily doses.
"Based on this phase I study, we feel there's a good chance that patients with BRCA-related cancers who meet the study eligibility criteria will have disease control for a meaningful period of time with relatively few side effects. However, randomized trials are necessary to demonstrate whether this will translate into improvements in progression-free and overall survival relative to currently available therapies," said Wainberg.
He and colleagues conducted a phase I trial to evaluate the safety and efficacy of BMN 673 in a two-stage dose escalation/expansion study. So far, they have recruited 39 and 41 patients to the escalation phase and expansion phase, respectively. Patients were 18-82 years old, and they had undergone one to 13 prior therapies.
Fifty participants18 with breast cancer, 28 with ovarian cancer, three with pancreatic cancer, and one with prostate cancerhad BRCA mutations in their tumors. Wainberg reported that to date, among the patients with BRCA mutations in their tumors, 44 percent of those with ovarian cancer and 44 percent with breast cancer had an objective response. Overall, 82 percent of the ovarian cancer patients and 72 percent of the breast cancer patients had clinical benefit (measured by imaging data and/or CA 125 levels for ovarian cancers and by imaging data for breast cancers).
In patients being treated at the 1 mg dose recommended for future trials, 50 percent of the breast cancer patients with BRCA mutations had an objective response and 86 percent had clinical benefit. Of the three patients with pancreatic cancer, two have had stable disease.
Fewer than 20 percent of the patients had grade 3 adverse events including fatigue, anemia, neutropenia, and thrombocytopenia, and one patient had a grade 4 toxicity.
Given the high objective and clinical benefit response rates in breast cancer patients, the investigators have recently initiated a phase 3 trial in metastatic breast cancer with BRCA mutations, according to Wainberg.
Among those with BRCA-unrelated cancers recruited to the phase 1 trial, one of the seven currently evaluable patients with small-cell lung cancer (SCLC) has responded, according to Wainberg. This patient, whose tumor metastasized extensively, has an ongoing partial response, he explained. "A solid partial response in a patient with SCLC provides some optimism about finding indications other than BRCA-related tumors that will benefit from treatment with BMN 673," he said.
###
This study was sponsored by BioMarin Pharmaceutical. Wainberg has no conflicts of interest to declare.
The 2013 International Conference on Molecular Targets and Cancer Therapeutics is being co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC).
This research will be presented at a press conference entitled "Guiding Treatment for BRAF- and BRCA-related Cancers" during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on Monday, Oct. 22 at 9 a.m. ET in room 202 of the Hynes Convention Center in Boston, Mass. Reporters who cannot attend in person may call in using the following numbers:
U.S./Canada (toll-free): 800-446-2782
International (toll): 847-413-3235
To interview Zev Wainberg, contact Shaun Mason at smason@mednet.ucla.edu or 310-206-2805. For other inquiries, contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109.
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org. Follow the AACR on Twitter: @AACR. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.
About the National Cancer Institute
The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
About the European Organisation for Research and Treatment of Cancer
The European Organisation for the Research and Treatment of Cancer (EORTC) brings together European cancer clinical research experts from all disciplines for trans-national collaboration. Both multinational and multidisciplinary, the EORTC Network comprises more than 2,500 collaborators from all disciplines involved in cancer treatment and research in more than 300 hospitals in over 30 countries. Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices.
EORTC Headquarters, a unique pan European clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run. http://www.eortc.org
Abstract Number: C295
Presenter: Zev A. Wainberg, M.D.
Title: Update on first-in-man trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors
Authors: Zev A. Wainberg1, Johann S. de Bono2, Lida Mina3, Jasgit Sachdev4, Lauren Averett Byers5, Rashmi Chugh6, Charlie Zhang7, Joshua W. Henshaw7, Andrew Dorr7, John Glaspy1, Ramesh Ramanathan4. 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; 3Indiana University, Indianapolis, IN; 4Virginia G. Piper Cancer Center at Scottsdale Healthcare/Tgen, Scottsdale, AZ; 5University of Texas MD Anderson Cancer Center, Houston, TX; 6University of Michigan, Ann Arbor, MI; 7BioMarin Pharmaceutical, Novato, CA
Background: BMN 673 is the most potent and specific inhibitor of PARP1/2 in clinical development (IC50Methods: Pharmacokinetics (PK), pharmacodynamics (PD), safety and anti-tumor activity of BMN 673 were evaluated in a 2-stage escalation/expansion study. Expansion included cohorts of pts with BRCA-related cancers, small cell lung cancer (SCLC) and Ewing sarcoma (ES).
Results: (As of July 29, 2013) In escalation, 39 pts were enrolled in 9 cohorts from 25 to 1100 g/d with 1000 g/d being the MTD related to dose-limiting hematologic toxicity. 38 pts have been enrolled in expansion including 25 patients with BRCA related cancers. For all 77 (63F/14M) pts, median age (range) is 52 (18-81), PS, 0 (0-1) and # of prior therapies 4 (1-13). Eight ES, 7 SCLC and 48 patients with deleterious BRCA mutations and breast (n=18), ovarian (n=28) or pancreatic (n=2) cancer were enrolled. BMN 673 demonstrated good oral bioavailability and a long half-life supporting daily dosing (ASCO 2013 Abstract 2580). One related grade 4 toxicity (thrombocytopenia) occurred. Related grade 3 adverse events have included fatigue, anemia, neutropenia and thrombocytopenia, all in fewer than 15% of patients. Dose-related inhibition of PARP activity in PBMC's was observed. Response, reduction in neutrophils and platelets and the need for blood transfusions and dose reductions appear to correlate with BMN 673 exposure.
^3 breast cancer responses are not yet confirmed; *CBR: clinical benefit response; **CA19-9 normalized in 1 patient
Overall, the objective response (including CA-125) and clinical benefit response rates are for all BRCA patients are 60.4% and 81%, respectively.
Treatment is ongoing in 5 of 7 SCLC patients and 2 of 8 ES patients with no objective responses observed yet.
Conclusions: BMN 673 is well tolerated with high objective and clinical benefit response rates in heavily pre-treated ovarian and breast cancer pts with deleterious germline BRCA mutations. A phase 3 trial in metastatic breast cancer is underway.
Clinicaltrial.gov ID: NCT01286987
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Share
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Israeli startup Appsee says it’s taking a different approach to mobile analytics.
I wrote about the company more than a year ago under its old name, UserVOD, when it focused on making video recordings of mobile app user activity. Now the company is launching a broader iOS analytics platform, where user recordings are just one feature.
So what’s Appsee actually doing differently? The company says most mobile businesses analyze their apps using “traditional metrics, such as number of downloads, number of daily users, and number of daily sessions, without understanding the full reasoning behind these figures.” The company adds:
With numerous analytics platforms only having a narrow set of app analytics tools that track and analyze these metrics, there is no true method in place for understanding user behavior. Typically developers must manually choose the measures they want to check, platforms do not usually identify and track everything automatically.
Appsee says that after customers add a single line of code to their app, the service will track every user session. Developer look at reports on those sessions using filters like churned users and first-time users, then drill down to a recording of a single session to see the actual behavior that’s attracting their interest, say a crash or whatever.
In addition, Appsee says it offers heatmaps showing where users touched each screen and makes automatic recommendations on how the interface and usability can be improved.
It seems publishers think Appsee is addressing a real problem here — the company says customers already include British Gas, My Supermarket, AppsFire, eToro, and Onavo (analytics company that was recently acquired by Facebook).
Appsee is also announcing that it has raised $1 million in funding from Giza Venture Capital and angel investors including Moshe Lichtman.
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