- Press Release Distribution

Dana-Farber leads adaptive, efficient multi-arm phase 2 clinical trial for glioblastoma

The trial could help researchers more quickly home in on effective treatments for this difficult to treat brain cancer

( EMBARGOED: September 18, 2023 4PM EST
CONTACT:  Nicole Oliverio,, 617-257-0454

Boston – An innovative phase 2 clinical trial led by Dana-Farber Cancer Institute in collaboration with 10 major brain tumor centers around the country and designed to find new potential treatments for glioblastoma has reported initial results in the Journal of Clinical Oncology. While none of the three therapeutics tested so far improved overall survival of patients, this adaptive platform trial, the first of its kind in neuro-oncology, has the potential to rapidly and efficiently identify therapies that benefit patients.

The trial, called INSIGhT, is still underway testing additional therapies.

“There have been many failed attempts to find better therapies for glioblastoma,” says co-first author Rifaquat Rahman, MD, a radiation oncologist at Dana-Farber. “This new trial design meets a need for a more efficient and smarter way to find new therapies.”

Patients with glioblastoma, the most common primary brain tumor, have few effective treatment options. Those with a form of the disease called MGMT unmethylated glioblastoma fare the worst and rarely respond to the standard therapy of radiation plus chemotherapy.

Traditionally, investigational therapies for glioblastoma are tested either head-to-head against standard therapy, or on their own in a single-arm trial with no control arm.

In contrast, INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) uses a shared control arm to test multiple investigational therapies at one time. So far, INSIGhT has tested a control arm of standard therapy against abemaciclib (a CDK4/6 inhibitor), neratinib (an EGFR/HER2 inhibitor), and CC-115 (a DNA-PK/mTOR inhibitor).

“This design is more economical and faster than the alternative of three separate randomized phase 2 trials, which would require many more patients and a lot more resources,” says co-senior author and principal investigator Patrick Wen, MD, Director of the Center for Neuro-Oncology at Dana-Farber.

In this first analysis of results, the trial enrolled 237 patients with newly diagnosed MGMT unmethylated glioblastoma between 2017 and 2021. Initially, patients were randomly assigned to receive one of the four treatments. Each patient had an 25% chance of receiving any one of the four options.

Once underway, the trial adapts to new information. Dana-Farber statisticians led by Lorenzo Trippa, PhD, continuously apply complex statistics to learn from each patient whether the drug they are receiving is having a likely benefit. The randomization algorithms enables future patients joining the trial to have increased odds of getting the best drug for them personally.

For instance, if patients experienced toxicities or no signs of benefit from a treatment option, future patients would be less likely to receive that treatment. If another treatment option showed benefit to patients, future patients would be more likely to be assigned to that option. The algorithm also factors in biomarkers associated with a likely benefit from a given therapeutic.

This approach, called Bayesian Adaptive Randomization, reduces the number of patients exposed to therapies that are unlikely to be successful. It also helps researchers put resources into therapies with the most promise.

“We can quickly stop pursuing drugs that are not promising and at the same time find the effective drugs and move them into phase three testing,” says Wen.

At the same time, the trial has set up an infrastructure that helps researchers learn more about why patients respond or do not respond to the therapies. This is one of the first trials in neuro-oncology to require tumor genomic sequencing up-front for all patients, which helps researchers learn more about how genetic biomarkers influence responses.

“It’s a very modern, science-enabling trial,” says co-senior author Keith Ligon, MD, PhD, a Dana-Farber pathologist and Chief of the Division of Neuropathology at Brigham and Women’s Hospital.

In this first readout of the trial, patients taking abemaciclib and neratinib experienced longer progression free survival than those receiving standard therapy or CC-115. None of the therapies extended overall survival.

The trial is designed to add new treatment arms. It is currently assigning new patients to either a novel brain penetrant chemotherapy (QBS10070S), an immunotherapy regimen consisting of a tumor vaccine VBI-1901 and a PD1 antibody, or standard therapy.

“This is a dynamic, evolving trial that will continue to test new therapies that could potentially benefit patients,” says Rahman. 

Testing a drug that has the potential to benefit patients with glioblastoma may be easier to do in the context of this trial because the trial is already established. Each new arm of the trial is an amendment to the trial, not a new trial itself.

“This trial is more streamlined, but it’s also rigorous, which makes it more likely that it will produce more reliable answers about whether or not a drug is worth further investment,” says Rahman.

The study’s other co-first authors were Eudocia Quant Lee from Dana-Farber and Isabel Arrillaga-Romany from Massachusetts General Hospital, and the other co-senior author was Brian Alexander from radiation oncology.

Funding: National Brain Tumor Society, Accelerated Brain Cancer Cure, Burroughs Wellcome Fund, Celgene Corporation, Puma Biotechnology, Inc., Eli Lilly and Company, Bristol Myers Squibb/Celgene.

About Dana-Farber Cancer Institute 

Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. Dana-Farber’s mission is to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber is a federally designated Comprehensive Cancer Center and a teaching affiliate of Harvard Medical School. 

We provide the latest treatments in cancer for adults through Dana-Farber Brigham Cancer Center and for children through Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber is the only hospital nationwide with a top 5 U.S. News & World Report Best Cancer Hospital ranking in both adult and pediatric care.

As a global leader in oncology, Dana-Farber is dedicated to a unique and equal balance between cancer research and care, translating the results of discovery into new treatments for patients locally and around the world, offering more than 1,100 clinical trials.





New research highlights importance of equity in education

New research highlights importance of equity in education
A new study looks at the impact of learning environments on the academic success of racialized students. Compared to their peers, these students feel they have less control in their academic environment, less confidence and self-efficacy in their academic abilities, and weaker connections to other students and professors. The University of Ottawa study underscores that higher education institutions must recognize and address the specific needs of their racialized student communities and create inclusive learning environments that better meet these needs. Failing to do so could affect the overall psychological well-being and academic performance ...

Cell therapy can reduce risk of death from COVID-19 by 60%, study shows

The use of cell therapy to treat COVID-19 patients can reduce the risk of death from the disease by 60%, according to a systematic review and meta-analysis conducted by researchers at the University of São Paulo (USP) in Brazil, in partnership with colleagues in Germany and the United States. Their findings are reported in an article published in the journal Frontiers in Immunology. The review covers 195 clinical trials of advanced cell therapies targeting COVID-19 that were conducted in 30 countries between January 2020 and December 2021, as well as 26 trials with outcomes published by July 2022. Cell therapy has come into increasingly frequent use in recent years ...

The pace of climate-driven extinction is accelerating, a UArizona-led study shows

The pace of climate-driven extinction is accelerating, a UArizona-led study shows
Climate change is causing extinctions at an increasing rate, a new study by the University of Arizona researchers shows. They surveyed populations of the Yarrow's spiny lizard in 18 mountain ranges in southeastern Arizona and analyzed the rate of climate-related extinction over time. "The magnitude of extinction we found over the past seven years was similar to that seen in other studies that spanned almost 70 years," said John J. Wiens, a professor in the Department of Ecology and Evolutionary Biology at UArizona, ...

Nuclear medicine treatment cures lethal form of ovarian cancer in preclinical setting

Nuclear medicine treatment cures lethal form of ovarian cancer in preclinical setting
Reston, VA—A new 225Ac-DOTA-based pre-targeted radioimmunotherapy (PRIT) system has been shown to cure a highly lethal form of advanced intraperitoneal ovarian cancer in a preclinical setting with minimal side effects. Targeting the HER2 protein, which is commonly expressed in ovarian cancer, the therapy (anti-HER2 225Ac-PRIT) is a potential treatment for the otherwise incurable disease. This research was published in the September issue of The Journal of Nuclear Medicine. Epithelial ovarian cancer is the most lethal ovarian cancer and frequently presents as advanced-stage disease, ...

Gene links exercise endurance, cold tolerance, and cellular maintenance in flies

EMBARGOED FOR RELEASE UNTIL September 18, 2023 at 3:00 PM U.S. Eastern time As the days get shorter and chillier in the northern hemisphere, those who choose to work out in the mornings might find it harder to get up and running. A new study in PNAS identifies a protein that, when missing, makes exercising in the cold that much harder—that is, at least in fruit flies. A team from University of Michigan Medical School and Wayne State University School of Medicine discovered the protein in flies, which they named Iditarod after the famous long distance dog sled across Alaska, while studying metabolism and the effect of stress on the body. They were particularly ...

Eureka baby! Groundbreaking study uncovers origin of ‘conscious awareness’

Eureka baby! Groundbreaking study uncovers origin of ‘conscious awareness’
Living things act with purpose. But where does purpose come from? How do humans make sense of their relation to the world and realize their ability to effect change? These fundamental questions of agency – acting with purpose – have perplexed some of the greatest minds in history including Sir Isaac Newton, Charles Darwin, Erwin Schrödinger and Niels Bohr. A Florida Atlantic University study reveals groundbreaking insight into the origins of agency using an unusual and largely untapped source – human babies. Since goal-directed action appears in the first months ...

Study finds human-driven mass extinction is eliminating entire branches of the tree of life

The passenger pigeon. The Tasmanian tiger. The Baiji, or Yangtze river dolphin. These rank among the best-known recent victims of what many scientists have declared the sixth mass extinction, as human actions are wiping out vertebrate animal species hundreds of times faster than they would otherwise disappear. Yet, a recent analysis from Stanford University and the National Autonomous University of Mexico, published this week in the Proceedings of the National Academy of Sciences, shows the crisis may run even deeper. Each of the three species above was also the ...

An implantable device could enable injection-free control of diabetes

An implantable device could enable injection-free control of diabetes
CAMBRIDGE, MA -- One promising approach to treating Type 1 diabetes is implanting pancreatic islet cells that can produce insulin when needed, which can free patients from giving themselves frequent insulin injections. However, one major obstacle to this approach is that once the cells are implanted, they eventually run out of oxygen and stop producing insulin. To overcome that hurdle, MIT engineers have designed a new implantable device that not only carries hundreds of thousands of insulin-producing islet cells, but also has its own on-board oxygen factory, which generates oxygen by splitting water vapor found in the body. The researchers showed that when ...

Buried ancient Roman glass formed substance with modern applications

Buried ancient Roman glass formed substance with modern applications
Some 2,000 years ago in ancient Rome, glass vessels carrying wine or water, or perhaps an exotic perfumes, tumble from a table in a marketplace, and shatter to pieces on the street. As centuries passed, the fragments were covered by layers of dust and soil and exposed to a continuous cycle of changes in temperature, moisture, and surrounding minerals. Now these tiny pieces of glass are being uncovered from construction sites and archaeological digs and reveal themselves to be something extraordinary. On their surface is a mosaic of iridescent colors of blue, green and orange, with some displaying shimmering gold-colored ...

Genomes of enigmatic tusk shells provide new insights into early Molluscan evolution

Genomes of enigmatic tusk shells provide new insights into early Molluscan evolution
Accurate phylogenetic trees are fundamental to evolutionary and comparative biology, but the almost simultaneous emergence of major animal phyla and diverse body plans during the Cambrian Explosion poses major challenges to reconstructing deep metazoan phylogenetic relationships. This is particularly true for the second largest phylum, Mollusca, whose major lineages originated in the Cambrian period. The diverse fossil record, extreme morphological disparity among the eight living classes, and dramatic conflict among phylogenetic hypotheses due to diverse paleontological, ...


Bioinformatics approach could help optimize soldiers’ training for improved readiness and recovery

Earth scientists describe a new kind of volcanic eruption

Warmer wetter climate predicted to bring societal and ecological impact to the Tibetan Plateau

Feeding infants peanut products protects against allergy into adolescence

Who will like beetle skewers? What Europeans think about alternative protein food

ETRI wins ‘iF Design Award’ for mobile collaborative robot

Combating carbon footprint: novel reactor system converts carbon dioxide into usable fuel

Investigating the origin of circatidal rhythms in freshwater snails

Altering cellular interactions around amyloid plaques may offer novel Alzheimer’s treatment strategies

Brain damage reveals part of the brain necessary for helping others

Surprising properties of elastic turbulence discovered

Study assesses cancer-related care at US hospitals predominantly serving minority populations compared with non-minority serving hospitals

First in-human investigator-initiated clinical trial to launch for refractory prostate cancer patients: Novel alpha therapy targets prostate-specific membrane antigen

Will generative AI change the way universities communicate?

Artificial Intelligence could help cure loneliness, says expert

Echidnapus identified from an ‘Age of Monotremes’

Semaglutide may protect kidney function in individuals with overweight or obesity and cardiovascular disease

New technique detects novel biomarkers for kidney diseases with nephrotic syndrome

Political elites take advantage of anti-partisan protests to disrupt politics

Tiny target discovered on RNA to short-circuit inflammation, UC Santa Cruz researchers find

Charge your laptop in a minute? Supercapacitors can help; new research offers clues

Scientists discover CO2 and CO ices in outskirts of solar system

Theory and experiment combine to shine a new light on proton spin

PKMYT1, a potential ‘Achilles heel’ of treatment resistant ER+ breast cancers with the poorest prognosis

PH-binding motifs as a platform for drug design: Lessons from protease-activated receptors (PARs)

Virginia Tech researcher creates new tool to move tiny bioparticles

On repeat: Biologists observe recurring evolutionary changes, over time, in stick insects

Understanding a broken heart

Genetic cause of rare childhood immune disorders discovered

With wobbling stars, astronomers gauge mass of 126 exoplanets and find 15 new ones

[] Dana-Farber leads adaptive, efficient multi-arm phase 2 clinical trial for glioblastoma
The trial could help researchers more quickly home in on effective treatments for this difficult to treat brain cancer