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Sunday, June 2, 2019

Nektar Presents Biomarker, Data from Phase 2 Melanoma Study

Nektar Therapeutics (Nasdaq: NKTR) announced today that biomarker and clinical data from PIVOT-02 is being presented at the 2019 American Society of Clinical Oncology (ASCO) Meeting in Chicago, Illinois.

New baseline biomarker analyses and updated clinical study efficacy and safety results were shared in a presentation titled, “Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab” (Abstract #2623/Poster Board #267) by Michael Hurwitz, Ph.D., M.D. who serves as Assistant Professor of Medicine, Medical Oncology at Yale Cancer Center during the “Developmental Immunotherapy and Tumor Immunobiology” poster session on Saturday, June 1, 2019.

“The Stage IV melanoma patients enrolled in the ongoing PIVOT-02 study continue to experience both deepening and durability of response over time,” said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar Therapeutics. “This translated into a 34% rate of complete response at a 12-month follow-up for the 38 efficacy-evaluable patients in this cohort. Further, 42% of patients achieved a 100% reduction in target lesions. Finally, corresponding lymphocyte data highlight the benefit of replenishing and stimulating T cells continuously over the course of treatment with an I-O doublet regimen.”

Bempegaldesleukin (NKTR-214, bempeg) is an investigational, CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 beta-gamma receptor. PIVOT-02 is an ongoing Phase 2 study evaluating bempeg in combination with nivolumab in solid tumors.

https://www.prnewswire.com/news-releases/nektar-therapeutics-presents-biomarker-and-clinical-data-from-pivot-02-phase-2-study-of-bempegaldesleukin-with-nivolumab-at-2019-asco-annual-meeting-300860219.html

ASCO: Merck details Keytruda’s second stomach cancer slip

Last month, Merck revealed that its Keytruda immunotherapy had run into more trouble in stomach cancer, a disease that’s given it difficulty in the past. And it shared the details of that stumble Saturday.

In previously untreated patients with advanced gastric or gastroesophageal junction cancer whose tumors bore biomarker PD-L1, adding Keytruda to chemo failed to improve on chemo alone, both in terms of extending patients’ lives and keeping cancer at bay. And that finding, presented at the American Society of Clinical Oncology annual meeting, held true regardless of patients’ PD-L1 levels.

Scot Ebbinghaus, M.D., vice president of clinical research at Merck Research Laboratories, couldn’t explain the flop for Keytruda, which has improved outcomes for patients when added to chemo in other cancers. In lung cancer, for instance, its addition slashed patients’ risk of death by half in a closely watched trial that rolled out last April.

But Ebbinghaus did characterize the results as a “relatively near miss,” noting the data “were in the right direction, just not quite there” in terms of statistical significance.

“There was a trend toward improving survival, but it didn’t reach” the threshold, he said.

Meanwhile, though, Keytruda did meet one endpoint in the study, dubbed Keynote-062. It showed it could measure up to chemo when used on its own in PD-L1 expressers, and in patients with high PD-L1 levels, it recorded a significant survival improvement. 39% of PD-L1-high patients were alive at the two-year mark, versus just 22% of those in the chemo group.

Merck was quick to highlight that success, and Ebbinghaus pointed to Keytruda’s potential as a chemo-free option that would help patients avoid the side effects associated with chemotherapy.

The data build on what’s been a checkered history for Keytruda in gastric cancer. Back in 2017, the superstar drug fell short of its primary endpoint in a second-line study, failing to either keep disease at bay or improve survival for previously treated patients with PD-L1-expressing tumors.

In the wake of that showing, Merck had been looking to Keynote-062 to confirm an accelerated approval it grabbed from the FDA in 2017. That green light cleared it for PD-L1-positive patients who have already received two other therapies. But now, the company will have to turn to other phase 3, frontline studies it has in the works.

https://www.fiercepharma.com/pharma/asco-merck-details-keytruda-s-second-stomach-cancer-slip

ASCO: Pfizer, Astellas’ Xtandi has more data for new prostate cancer approval

Pfizer and Astellas’ Xtandi is gunning for a new indication in prostate cancer, and they say Sunday’s new data complement the supporting evidence they’ve already generated.

Sunday at the American Society of Clinical Oncology annual meeting, researchers trumpeted data from an investigator-sponsored study in metastatic hormone-sensitive prostate cancer (mHSPC). The study showed Xtandi slashed the risk of death by 33% compared with other non-steroidal androgen-fighting meds.

Eighty percent of men taking the Pfizer-Astellas drug were alive after three years compared with 72% of men who received the hormone-based chemo drugs bicalutamide, nilutamide or flutamide alongside standard treatment.

The results from the phase 3 study, dubbed Enzamet and led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group, back up the companies’ own results from the phase 3 Arches trial. “The two studies actually are complementary of one another,” said Andrew Krivoshik, M.D., Astellas’ vice president of medical science for oncology. The types of patients overlapped, but endpoints and eligibility criteria differed, he said.

And both studies will help support Pfizer and Astellas’ regulatory filing for a label expansion, Andy Schmeltz, global president and general manager of Pfizer Oncology, said.

“We think the totality of the data together makes a pretty compelling platform for physicians to consider Xtandi, assuming it gets approved, in this patient population,” he added.

Arches, detailed in February, showed that combining Xtandi and androgen deprivation therapy (ADT) cut the risk of cancer worsening or death by 61% versus ADT alone. At the time of analysis, patients in the ADT-only group had gone a median 19.4 months before showing evidence of radiographic disease progression, an endpoint commonly used in prostate cancer trials. Meanwhile, in the Xtandi-ADT group, the median hadn’t yet been reached.

At the time, Pfizer and Astellas said they’d take the results to regulators worldwide, aiming to tack an HSPC nod onto Xtandi’s list of approved uses. Right now, the product is cleared only in castration-resistant prostate cancer.

And given Xtandi’s prostate market battle with Johnson & Johnson treatments Zytiga and Erleada, the partners wouldn’t mind a sales boost; the drug’s $168 million in first-quarter sales missed Wall Street’s $186 million prediction. Pfizer biopharma President Angela Hwang cited inventory differences and Pfizer’s free drug program among reasons Xtandi’s revenues have been lagging behind demand.

https://www.fiercepharma.com/pharma/asco-pfizer-astellas-xtandi-racks-up-more-data-for-new-prostate-cancer-use

ASCO Day 3 notables

It looks like testing for germline (inherited) mutations is going to be increasingly important in pancreatic cancer.

As ASCO experts pointed out to me in this morning’s press briefing, the technology is available and could identify patients with the BRCA mutations who could respond to treatment with PARP inhibitors.

Testing for somatic BRCA-like mutations that arise as the disease progresses could also be feasible in the future.

an hour ago

Here’s some more from my interview with Merck & Co’s Dr Roy Baynes, who discussed the long-term findings of the KEYNOTE-001 data announced yesterday.

Findings were summarised in yesterday’s blog – but headline data was that after a median follow-up of 60.6 months – around five years – and at that point 18% of enrolees (100 people) were still alive.

Of those who had not received prior treatment, 23% were still alive after five years compared with 15.5% of those previously treated.

Dr Baynes said: “These were metastatic lung cancer patients. When I was training, the vast majority of metastatic lung cancer patients would be dead after five years.”

Before immunotherapy the survival rate was about 5%, but Dr Baynes pointed out that there has been a “five-fold improvement in outcomes.”

“Depending on the group of patients that you study the five-year survival is somewhere between 15% in the pretreated population in the salvage situation and around 25% in the front-line population.

“If you look at the PD-L1 strongly positive (a biomarker for immunotherapies) it’s almost 30% so huge change from the time when maybe one in 20 patients survived.

“Somewhere between one in five, one in four, one in three patients surviving after five years, so that’s a huge change in what the cancer patient can expect.”

2 hours ago

ASCO’s experts may have fudged this issue slightly this morning.

But there was plenty of reaction to the data on how Obamacare addressed racial inequality in access to cancer care when it was highlighted in a plenary session.

2 hours ago

Stressed-out cancer cells

The results in pancreatic cancer from Merck & Co/AstraZeneca’s Lynparza came from a PARP inhibitor.

The principle behind this drug is to interfere with the DNA damage repair system that certain cancer cells need to survive.

DNA damage repair is just one of several stress-relieving strategies adopted by cancer cells.

Joan Brugge director of the Harvard Ludwig Cancer Center and professor of Cell Biology at Harvard Medical School gave a fascinating talk about how drug companies could target these stress-relieving mechanisms to treat the disease.

Targeting multiple stress relieving programmes will also be highly selective for cancer cells as healthy cells don’t have these mechanisms in operation.

They could also integrate with immunotherapy for an even more powerful effect.

2 hours ago

3 hours ago

More of that data from Sanofi about isatuximab, which is being tested in combination with Celgene’s Pomalyst (pomalidomide) and dexamethasone in multiple myeloma.

Progression free survival (PFS) was 11.53 months on the isatuximab combination compared with 6.47 months on Pomalyst and dexa standard care – with a nice highly significant p-value of 0.001.

Compared to pomalidomide and dexamethasone alone, isatuximab combination therapy demonstrated a significantly greater overall response rate (60% vs. 35%) with an even better p value of 0.0001

In additional analyses, isatuximab combination therapy compared to pomalidomide and dexamethasone alone showed a consistent treatment benefit in the following subgroups: patients 75 years and older, patients with renal insufficiency, and patients who were refractory to lenalidomide. Results were confirmed by independent review committee.

Overall survival data is not ready yet by Sanofi said there is a trend towards isatuximab combination compared with standard care.

Sanofi’s combination also showed a shorter median time to first response versus pomalidomide and dexamethasone alone (35 days vs. 60 days).

3 hours ago

I just caught up with Dr Roy Baynes, chief medical officer at Merck Research Laboratories, and asked him about the data from AZ/Merck & Co’s Lynparza (olaparib) in pancreatic cancer, among other things.

The companies are developing the drug in partnership and equally share development and marketing costs, as well as profits.

While the efficacy data was strong from the POLO trial, there were some side effects with 40% of people experiencing serious side effects compared with 23% in a placebo arm.

I asked him whether this could be an issue with regulators during their reviews in this indication.

Dr Baynes said: “All drugs are going to have side effects, and if you look at discontinuation it was very uncommon. Despite an adverse event profile, much of which is on-target, anaemia, the vast majority of patients stayed on treatment.”

We also discussed the lack of overall survival data so far from POLO – this is caused by the number of patients who are still alive on this trial.

“If you look at most of the PARP inhibition data that we have generated, it really has been about progression free survival. It’s really important, it means you are not going on to some other treatment, you are not progressing and most people see this as an important clinical benefit,” he said.

He also pointed out that a small percentage of pancreatic cancer patients could be treated with Merck & Co’s Keytruda (pembrolizumab) immunotherapy if the tumour possesses “MSI-High” mutations – one of the drug’s many indications.

3 hours ago

Sanofi announced results from the first Phase 3 study of isatuximab, an investigational antibody treatment, used in combination with pomalidomide and dexamethasone, to treat people living with multiple myeloma.

It’s the second most common haematological cancer, is uncurable and characterized by multiple relapses.

The results, presented by Sanofi today showed isatuximab combination therapy prolonged the length of time a patient lived without their cancer getting worse (progression free survival) by more than five months compared to Celgene’s Pomalyst (pomalidomideP) and dexamethasone alone.

Overall response rate with isatuximab combination therapy was almost double that of the response rate seen with pomalidomide and dexamethasone alone.

4 hours ago

5 hours ago

In a session on health equality Dr Robin Vanderpool highlighted some of the disparities in cancer care that affect rural communities.

These include the ‘tyranny of distance’, where cancer patients live more than 50 miles away from a hospital, and a range of socioeconomic disparities.

Dr Vanderpool was earlier this year appointed director for community outreach and engagement at the Lexington, Kentucky-based Markey Cancer Center.

Sanofi names ex-Roche cancer guru Dietmar Berger as development lead

Roche alumnus Dietmar Berger has joined Sanofi as head of development following a short stint in biotech.

In his new role Berger will oversee the company’s clinical portfolio across all therapeutic areas to help bring new medicines to patients.

Last year Berger became one of several Big Pharma names to make the jump to biotech, taking a role as global head of research and development at T-cell immunotherapy biotech Atara Biotherapeutics.

He held this position for a relatively short time, having started in May 2018 and resigning last week when Atara got a new CEO in the form of Pascal Touchon, formerly of Novartis.

Prior to joining Atara, Berger was senior vice president and global head, product development, clinical science hematology and oncology at Roche/Genentech – and before that was vice president of global clinical development for the company’s HER2 breast cancer franchise.

Berger leant his expertise to filings of some of Roche’s most important new drugs – such as the cancer immunotherapy Tecentriq and the potential blockbuster in haemophilia, Hemlibra.

But it seemed that Roche’s decision not to develop any T-cell therapies of its own – choosing instead to combine Tecentriq (atezolizumab) with cell therapies from Kite/Gilead under a deal announced in 2016 – eventually led Berger to be tempted away to a more specialist company focusing on this promising area.

The new job will see him reunited with John Reed, formerly head of the Pharma Research and Early Development (pRED) unit at Roche and now Sanofi’s global head of R&D.

Previously Berger led oncology clinical development at Bayer and held positions of increasing responsibility at Amgen.

He has also led research groups focusing on preclinical drug development, tumor models, angiogenesis, and immunotherapy as head of the Clinical Research Center at the University Medical Hospital, Freiburg, Germany, and at The Scripps Research Institute, La Jolla, California. He received the Cancer Award of the German Cancer Society for his research on angiogenesis and earned his M.D. and Ph.D. degrees from the University of Freiburg.

Sanofi names ex-Roche cancer guru Dietmar Berger as development lead

Mitsubishi Tanabe pulls ALS drug from European assessment

Mitsubishi Tanabe Pharma has withdrawn its EU application for ALS drug Radicava (edaravone), citing ‘unwarranted’ additional data requirements from the EMA.

The drug has been approved in the US, Japan, South Korea, Canada and Switzerland based on results from a a six month trial in Japan involving 137 people that showed those taking Radicava declined less on a clinical assessment compared with those receiving placebo.

However, the EMA’s Committee for Medicinal Products for Human Use (CHMP) has said than an additional study of survival, lasting at least 12 months, would be required to obtain the data necessary for regulatory approval in the EU.

In a statement Mitsubishi Tanabe said it believes “that the efficacy and safety of edaravone has been demonstrated and an additional long-term study is unwarranted”.

Therefore, the company said it “has made the difficult decision to withdraw the marketing authorisation application for edaravone” and “will now carefully consider the future options for edaravone in the EU”.

The company added that it will “continue to make every effort to deliver edaravone to patients suffering from ALS worldwide by increasing, as far as possible, the number of countries with regulator approvals based on current data”.

Radicava is an intravenous infusion given by a healthcare professional. It is administered with a first treatment cycle of daily dosing for 14 days, followed by a 14-day drug-free period.

Subsequent cycles consist of dosing on 10 of 14 days, followed by 14 days drug-free.

Mitsubishi Tanabe is also developing an oral formulation of the drug as an option to supplement the existing IV formulation.

Radicava was the first ALS treatment approved by the FDA in more than 20 years. The Association asked the manufacturer to file its drug upon learning about its use to treat ALS in Japan.

The drug does, however, come with a raised risk of serious side effects such as hives, swelling, or shortness of breath, and potentially life-threatening allergic reactions to sodium bisulfite.

And as ever there is the issue of cost – the annual cost before any discount is more than $145,500.

Mitsubishi Tanabe pulls ALS drug from EMA assessment

ASCO, Partners Aim to Create Core Cancer Model, EHR Data Elements

Almost 40% of Americans will be diagnosed with cancer at some point in their lifetime. But only 3% of adult cancer patients participate in clinical trials, which gather most of the high-quality data used for cancer research. That’s not enough data to quickly lead to better treatments and results.

What if we could learn from the experiences of the other 97% of patients representing all demographics? What if we could explore the data from millions of patients and study the myriad combinations and comparisons of treatment parameters to provide substantial insights on the best treatment for each patient?

Data from most of the nearly 15 million individuals living with cancer in the U.S. is contained in electronic health records (EHRs) of some kind. But many EHR systems in use prioritize the collection of different types of data, use different terms to describe the same type of data, or collect data in different formats, making them incompatible with one another. This incompatibility dramatically limits the ability of cancer researchers and doctors to learn from patient records, hinders care coordination, and adds to the administrative burdens and costs for all users, but especially practices and patients.

That’s why we need mCODE.

We See the Possibilities

Every interaction between a clinician and a cancer patient provides high-quality data that could lead to safer care, improved outcomes, and lower costs. But first we need data that is:

Standardized and collected in a computable manner so it can be aggregated with data from many other patients and analyzed for best practices
Exchanged through EHR systems that are interoperable
Collected in a streamlined way that doesn’t burden the clinicians
Secure and protects patient privacy

We Can Make This Happen

The American Society of Clinical Oncology (ASCO) and its nonprofit subsidiary, CancerLinQ LLC, and The MITRE Corporation are collaborating to develop and launch mCODE. We have identified those minimal cancer data elements that are essential for analyzing patient characteristics, treatments, and outcomes across patients and practices to improve treatment and care coordination.

mCODE provides both a common data language and an open source, nonproprietary data model for interconnectivity across systems. Once adopted across the oncology community, mCODE can facilitate the ability of clinicians and researchers to provide better treatments for cancer patients by using the invaluable information contained in the EHRs.

Every Patient’s Journey Can Improve All Future Care

Interested in joining the mCODE Council? Submit your application online.

Downloadable Information on mCODE

The mCODE data specification is made available on an open source basis. We ask requesters to provide their contact information to better understand the potential user base, which will help us tailor use cases and features for future development. Also, we will notify you of updates and other relevant information on mCODE. (This is optional, and you can opt out of our email list at any time.)

https://mcodeinitiative.org/

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Sunday, June 2, 2019

Every Patient’s Journey Can Improve All Future Care

Downloadable Information on mCODE