Search This Blog

Saturday, September 10, 2022

Erasca Touts Promising Early Data From Lead Cancer Programs

 

  • Erasca Inc  announced preliminary Phase 1/1b monotherapy data for ERAS-007 and ERAS-601 in solid tumor settings.
  • A retrospective pooled analysis of all trials evaluating ERAS-007 or ERAS-601 in advanced solid tumors included Erasca's ongoing HERKULES-1 and FLAGSHP-1 trials and Asana BioSciences' previously completed ASN007-101 trial. 
  • Key findings from the retrospective pooled interim analysis of ERAS-007 and ERAS-601 show that 23% (6/26) of patients with RAS/MAPK-altered non-colorectal cancer (CRC) solid tumors responded (2 confirmed and four unconfirmed PRs) to single agent ERAS-007 or ERAS-601.
  • 44% (4/9) with a subset of BRAF-driven non-CRC solid tumors responded (1 confirmed and three unconfirmed PRs).
  • ERAS-007 and ERAS-601 had favorable safety and tolerability monotherapy profiles with largely non-overlapping treatment-related adverse events that support combination development.
  • Recently, Erasca announced a partnership with The University of Texas MD Anderson Cancer Center to evaluate multiple agents from Erasca's pipeline targeting the RAS/MAPK pathway as either single-agent or combination therapies.
  • Under the terms of the five-year agreement, collaborative preclinical and clinical studies will be conducted in NSCLC and GI malignancies.
  • The company will initiate a dose escalation trial for ERAS-007 in combination with ERAS-601 in the first half of 2023.

Exelixis: Results From Late-Stage Cabometyx Combo Trial In Kidney Cancer

 

  • Exelixis Inc  announced detailed results from the COSMIC-313 Phase 3 trial cabozantinib (Cabometyx), nivolumab, and ipilimumab combo in untreated advanced renal cell carcinoma (RCC) patients. 
  • The data are being presented at the 2022 European Society of Medical Oncology (ESMO) Congress.
  • As previously announced, the cabozantinib combination significantly reduced the risk of disease progression or death compared with the combination of nivolumab and ipilimumab.
  • The cabozantinib combination versus the combination of nivolumab and ipilimumab did not demonstrate a significant benefit in overall survival (OS). Therefore, the trial will continue to the next analysis of OS.
  • The median progression-free survival (PFS) was not reached for the combination of cabozantinib, nivolumab, and ipilimumab and was 11.3 months for the nivolumab + ipilimumab combo.
  • Objective response rates in the PFS intent-to-treat population were 43% and 36%, respectively. The median duration of response was not reached in either treatment arm. PFS subgroup analyses will also be presented at the ESMO meeting.
  • The safety profile observed in the trial reflected the known safety profiles for every single agent and the combination regimens used in this study. No new safety signals were identified.

Violence is common and increasing in pandemic-era California

 Violence is on the rise in California, with significant increases observed during the COVID-19 pandemic, according to the latest annual report from the California Study on Violence Experiences across the Lifespan (CalVEX). Led by researchers at University of California San Diego School of Medicine, CalVEX is the nation’s only multi-year statewide assessment of violent experiences.

The findings, shared in a public report on September 8, 2022, reveal that more than one in six Californians (18 percent) experienced physical or sexual violence in the past year, and one in every 25 Californians experienced intimate partner violence. Rates of both physical and sexual violence have increased since the start of the pandemic, with physical violence nearly doubling for men from 2020 to 2022. Further demographic disparities highlight potential contributing factors that may have been exacerbated by the pandemic. 

“Californians are experiencing violence at epidemic proportions,” said principal investigator Anita Raj, PhD, professor at University of California San Diego School of Medicine and Division of Social Sciences. “Current violence prevention efforts are clearly woefully inadequate and often ignore the gendered nature of violence, its intersections with other socioeconomic vulnerabilities and its disproportionate effects on marginalized populations.” 

The majority of victims never formally report these experiences, so researchers say relying on criminal justice data or health records to examine the state of violence often fails to capture the true breadth of abuses. Instead, CalVEX surveys a representative sample of adults across the state and uses their responses to estimate population rates. Data in the latest report were collected in March 2022 from 2,285 adults.

The results reveal various gender disparities in the experience and perpetration of violence. Men are more likely than women to have faced physical violence, whereas women are more likely than men to have experienced many forms of sexual violence. While more than 1.5 million adults in California admit to committing acts of sexual violence in the past year, men were more than two times as likely as women to report that they perpetrated sexual violence and intimate partner violence. 

Women also showed greater mental health impacts and life disruptions due to violent experiences, with 82 percent of women reporting anxiety or depression as a result of physically aggressive, coercive or forced sexual behavior. Women who reported physical violence were also twice as likely as men to miss work or school as well as change or quit a job. 

Socially and economically vulnerable Californians — including Latino and Black communities, LGBTQ communities, people with a history of homelessness or incarceration, and people living with a disability — also faced disproportionate levels of violence. Experiences of financial distress, including eviction and food or housing insecurity, were associated with a two to eight times increased risk of violence. 

“Our findings suggest the rising rates of violence are linked to the harsher social climate, economic insecurity, and poorer physical and mental health that many Californians have experienced over the last few years due to the pandemic,” said Raj.

The researchers advocate for new policies that strengthen social and economic safety nets, programs in violence prevention, and mental health services across the state. Such a multi-level approach, Raj says, would not only address the current violence crisis, but also support post-pandemic rebuilding and make the state more resilient to other health, environmental and socioeconomic stressors to come.

Co-authors of the report include Nicole E. Johns, Nabamallika Dehingia, Wendy Wei Chang and Jennifer Yore, all at UC San Diego. 

https://www.eurekalert.org/news-releases/964210

Push to double up on Covid booster and flu shot may have a downside

 As the promotional push to get people vaccinated with one of the updated, bivalent Covid vaccines heats up, federal health authorities are urging Americans to consider getting their Covid shot and their flu shot at the same time. And with concern about a fall wave of Covid paramount in this effort, the messaging is stressing the importance of doing this sooner rather than later.

Earlier this week, Anthony Fauci, President Biden’s chief medical adviser, put it bluntly: “Get your updated Covid-19 shot as soon as you are eligible.” For many people over the age of 12, that would be right now.

There’s just one problem with the advice. It’s still early to get a flu shot.

The protection generated by influenza vaccines erodes pretty quickly over the course of a flu season. A vaccine dose given in early September may offer limited protection if the flu season doesn’t peak until February or even March, as it did during the unusually late 2021-2022 season.

“If you start now, I am not a big fan of it,” Florian Krammer, an influenza expert at Mount Sinai School of Medicine in New York, told STAT. “I understand why this is promoted, but from an immunological point of view it doesn’t make much sense.”

A number of studies have shown that the benefit of a flu shot wanes substantially over the course of a flu season — exacerbating effectiveness problems that are frequently seen when some of the strains in the vaccine aren’t well matched to the strains making people sick.

Work done by researchers from the Kaiser Permanente Vaccine Study Center and the Harvard School of Public Health estimated vaccine effectiveness declined by about 18% for every 28-day period after vaccination. A study done by scientists at the Centers for Disease Control and Prevention and elsewhere showed that the vaccine’s protection against flu that is severe enough to trigger hospitalization decreases by between 8% and 9% per month after vaccination. In older adults, who are more likely to get seriously ill from flu, the decline happened at a rate of about 10% to 11% per month.

“You’ve got about four months of pretty solid protection,” said Emily Martin, an associate professor of epidemiology who specializes in flu at the University of Michigan School of Public Health. Martin was an author on the latter study.

If you ask someone who researches flu and flu vaccines, they will likely quietly — or in some cases, not so quietly — advise you to wait at least until the end of October to get a flu shot, though they’ll attach the caveat that if you start to hear about flu activity picking up where you live, you should fast-forward your plans.

“I’ll follow very carefully the activity in the community,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy. “If it starts to pick up, I’ll move immediately. Otherwise I’m counting on sometime in late October, early November.”

Martin gets her flu shot every October two weeks before a scientific meeting she attends, unless she hears something that makes her rethink that timing. “I’m right across the street from a dorm,” she said. “As soon as I start seeing those flu numbers go up, I’ll go get it.”

Krammer waits longer. “I usually get the flu shot at the end of November, because typically we see a rise in cases in the middle of December, and by then my antibody response should have kicked in, and be at its prime for a December-January season, and there might still be enough for a late season,” he said.

The CDC’s official advice states that “September and October are generally good times to be vaccinated against flu,” though the agency’s website adds that “ideally, everyone should be vaccinated by the end of October.”

The “everyone” thing is one of the sticking points when trying to time flu vaccinations. While waiting would generally make more sense on an individual basis, the goal most years is to get flu shots into tens of millions of arms over a period of a few weeks. That’s a big task for the health care system when it’s just flu, but this fall, vaccine deliverers are trying to get Covid boosters and flu shots into as many arms as possible.

Noel Brewer, a professor of health behavior at the University of North Carolina, said he thinks moving to this joint-administration approach is the right idea. Covid vaccine delivery has been overly complicated, he said, requiring people to keep track of too many things. How many shots they’ve had. When they last had a shot. When they are next eligible for a shot.

People have been tuning out, he said — an assertion bolstered by the booster uptake rate. The percentage of eligible people who got a second Covid booster is lower than the percentage of people who got a first booster, which is lower than the percentage of people who got a primary series of two shots.

Making things simple and pairing Covid shots with another health intervention makes it easier for people, Brewer said — even if the combination benefits one of the interventions more than the other.

“I don’t think any of this is free. I don’t think any of it’s easy,” he said. “There isn’t a single best option that we can do that doesn’t have some consequences. We just have to take the less onerous consequence.”

Ed Belongia, director of the Center for Clinical Epidemiology and Population Health at Wisconsin’s Marshfield Clinic Research Institute, said in a case like this, public health authorities need to think in terms of what works best for the collective, not each individual in it.

Some people get flu shots every year; they are motivated to take advantage of this preventive tool. Some of them may well decide to book a flu shot appointment for later in the fall rather than get their flu shot when they get a Covid booster. Belongia is among them. He’d rather wait a while and he’s planning on getting a high-dose flu shot, which will probably have more side effects than the standard vaccine. While getting flu and Covid shots during the same health care visit is safe, Covid shots can carry quite a kick. Belongia would prefer to get the two vaccines separately.

But other people are unlikely to book two health appointments to get two different shots, authorities realize from experience with other health interventions. Given that reality, what’s ideal may have to give way to what’s pragmatic.

“There’s a tradeoff, right, between starting too early and having waning, versus missing opportunities to vaccinate,” said Belongia. “In terms of trying to optimize timing, you lose people who don’t get vaccinated at all. Trying to balance those is difficult because you don’t know when the flu season is going to begin each year.”

That is the other key sticking point with advising people on when to get a flu shot. Ideally, getting vaccinated shortly before flu season starts to take off would make sense. Estimating when flu season is going to take off — well, good luck with that.

“Trying to predict flu seasons is in many cases a lot harder than predicting the stock market,” Osterholm said.

Influenza is notoriously variable. In many years, activity only really comes to a head in January and February, but in 2021-2022, the week of peak activity was the week between Christmas and New Year’s. That said, there was a long tail to the 2021-2022 season, with cases remaining at atypical levels in June.

Figuring out what flu is going to do — when it’s going to hit, which subtype will be dominant, whether the season will be tough or mild — is even harder in the pandemic era. Covid wiped a lot of pathogens off the table for a time. There was no flu season to speak of in 2020-2021, and while the 2021-2022 season was unusually extended, it was mild.

Some of the bugs that stopped circulating in the early part of the pandemic have come back with a vengeance, and scientists worry that the same will be true when flu activity returns to pre-pandemic levels. In a recent interview with Bloomberg News, Fauci warned the country might be facing a “pretty bad flu season.”

Flu experts think that’s possible, but not guaranteed.

“If I had to predict, I do think, whether this year or in future years, sooner or later the immunity debt is going to catch up with us, particularly younger folks,” Martin said. “You’ve got entire birth cohorts of children growing into the population that haven’t had that regular introduction to viruses that they normally would have had between the years 0 and 3.”

Little kids play a pivotal role in spreading flu around communities. “They’re little bioreactors, right?” said Krammer.

People often look to the southern hemisphere to try to predict the coming winter’s flu activity, though what happens north of the equator doesn’t alway match what happened south of it.

This year Australia had a very active flu season, akin to pre-pandemic seasons, Kanta Subbarao, director of the World Health Organization’s Collaborating Center for Reference and Research on Influenza in Melbourne, Australia, said via email. Though most of the activity was caused by the influenza A virus H3N2 — a virus that is typically very hard on older adults — children were most affected this year, Subbarao said.

Elsewhere in the southern hemisphere, the flu season was not particularly active, said Osterholm, who suggested it’s not yet clear what we’re facing, influenza-wise.

“All I can do is say based on a typical year, 1) you don’t want to get the vaccine too early and 2) we could see everything from a mild to a severe flu season and everything in between and we don’t know,” he said. “And the best way to be prepared for that is to try to time your vaccination to what a typical winter season incidence looks like. And that means to me, mid-October to early November, and of course, always being open to change if we see unusual early activity.”

https://www.statnews.com/2022/09/09/doubling-up-on-covid-booster-flu-shot-may-have-downside/

The Secret Curriculum

By Betsy McCaughey 

School is starting, but don't count on getting answers about what your child is being taught. School administrators commonly lie or give parents the runaround.

That explains the fireworks over Jeremy Boland, a Greenwich, Connecticut, elementary school assistant principal, bragging about how the school pushes kids to think in a "progressive" way that he hopes will make them Democratic voters.

The school's hiring process, he explains in a video, is geared to accomplish indoctrination. Prospective teachers who are Catholics or over 30 are disqualified. They're too set in their ways, he says. Catholics are unlikely to "acknowledge a child's gender preferences" or go against parents. He says, "You don't hire them."

When the video was released last week, Greenwich authorities immediately put their free-speaking assistant principal on leave. But Peter Sherr, who served on the Greenwich Board of Education for 12 years until last December, attests that Boland's comments are very accurate. "I can say with a high degree of confidence that Mr. Boland is not alone," he said.

The video, made by the undercover investigative nonprofit Project Veritas, is part of a "Secret Curriculum" series. Another video shows Jenn Norris, director of student activities at New York City's Trinity School, swearing she'd never allow a Republican speaker at the school. "Not on my watch."

Secrecy is a problem across the country. Officials discourage parents' inquiries and throw up roadblocks to those who persist.

Jackie Homan, who has three sons at Greenwich High School, says when she questioned the curriculum at a Board of Education meeting, "they laughed me out of the room." She filed Freedom of Information Act requests, and after months of runaround, got some information, but not about the class that worried her the most -- SEL, short for social and emotional learning.

She was told she couldn't have a copy of the SEL curriculum because it was copyrighted -- a preposterous excuse because all the books students read are copyrighted.

The West Perry School District in Pennsylvania used the same lame excuse to turn away another inquiring mother, Ashley Weaver.

When a Fort Worth, Texas, mother, Jenny Crossland, requested a list of books her children were being assigned, the school district told her she'd have to pay $1,267.50 for someone to compile it.

SEL classes are shrouded in secrecy. It's no wonder. Originally, social and emotional learning meant teaching children to control their emotions and get along in class. No more. Now, K-12 students are being taught "transformative SEL." The American Federation of Teachers says the new SEL is aimed at "redistributing power to promote social justice."

Panorama Education, a for-profit company that produces SEL materials for 1,500 school districts across the country, and the nonprofit CASEL, the largest producer of SEL materials, both encourage students to see systemic racism in their world.

SEL is political indoctrination. In many schools, students have SEL classes several times a week, even replacing math or science.

Last week, the West Bonner, Idaho, school district canceled its English language curriculum in response to parent protests that the SEL component would lead to liberal indoctrination and the teaching of critical race theory.

Parents are catching on, but too slowly. Public education is being hijacked. The American Federation of Teachers, the second largest teachers union, announced its goal is to "reimagine the purpose of education" from learning to social activism. Never mind if your child acquires the skills to succeed.

Teacher training programs and graduate schools of education have stopped focusing on classroom management, lesson planning and pedagogy. Fewer than one in four emphasizes training teachers in the "science of reading." The new focus is how to turn children into activists.

No wonder Boland said his school will only hire teachers under age 30. They're ready-made indoctrinators.

Boland got caught in a gotcha undercover video. It shouldn't be that tricky to get the truth. The heroes are parents who keep demanding the truth, even when school authorities laugh them out of the room.

President Joe Biden told a group of teachers that their students "are not somebody else's children. They're like yours when they're in the classroom." Sorry, Mr. President. They're yours to educate, but not to indoctrinate.

https://www.realclearpolitics.com/articles/2022/09/10/the_secret_curriculum_148155.html