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Saturday, June 1, 2019

ASCO 2019 day 3

Exclusive live coverage from day three of the American Society of Clinical Oncology’s annual meeting in Chicago.

• To view all of our coverage from the preeminent cancer event, produced in association with Kantar Health, as well as additional content, visit the Spotlight on ASCO 2019 and the future of oncology

Key highlights for Sunday include:

AstraZeneca/Merck & Co will provide one of the highlights of Sunday at ASCO, with data from the phase 3 POLO trial as a maintenance treatment in metastatic pancreatic cancer with germline BRCA mutation. This will flesh out a top-line positive result announced earlier this year.
Novartis also has data from alpelisib, a PIK3CA class drug in patients with breast cancer. With this drug Novartis is hoping to succeed where its Swiss rival Roche has failed. Last year Roche ditched its PIK3CA drug taselisib after deciding trial data showed unpleasant side-effects would outweigh its very limited benefits in eligible patients with breast cancer. Novartis will also have further data from its breast cancer drug Kisqali.
Also on Sunday, Roche will present early data from its “tumour agnostic” drug entrectinib in children with recurrent or refractory solid tumours, including central nervous system tumours.

ASCO 2019 day three

Kite Winds Up Phase 1 of Leukemia Med Trial

— Data Show High Rates of Response to Single Infusion of KTE-X19 —

— Phase 2 Portion of ZUMA-3 is Ongoing and Includes Dosing and Revised Safety Management Protocol Studied in Phase 1 —

Kite, a Gilead Company (Nasdaq: GILD), today announced results from the completed Phase 1 of the ZUMA-3 study evaluating KTE-X19, an investigational CD19 chimeric antigen receptor T (CAR T) cell therapy. ZUMA-3 is a single-arm Phase 1/2 study in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL). The results provide guidance on dosing and safety management for KTE-X19 to inform the ongoing Phase 2 study. The data were presented during an oral session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, May 31 – June 4 (Abstract #7006).

https://www.marketscreener.com/GILEAD-SCIENCES-4876/news/Gilead-Sciences-Kite-Announces-End-of-Phase-1-ZUMA-3-Results-for-KTE-X19-in-Adult-Patients-with-Re-28692908/

J&J reps said to have blanketed Okla. docs with promos later called false, misleading

Promotional materials that the U.S. Food and Drug Administration would later label “false or misleading” were repeatedly used by Johnson & Johnson sales representatives to promote the company’s opioid Duragesic patch to Oklahoma doctors in the early 2000s.

That troubling fact was made clear Friday morning as an attorney for the state quizzed a Johnson & Johnson corporate representative for nearly three hours about the contents of call notes made by the sales representatives following more than 60 sales visits to physicians in offices scattered throughout Oklahoma.

The testimony came on Day 4 in a Cleveland County District Court trial in a case where Oklahoma Attorney General Mike Hunter has accused Johnson & Johnson and its subsidiaries of creating a public nuisance through false marketing that downplayed the risks of their opioid painkillers while overstating their benefits. The state has accused the companies of helping cause an opioid epidemic that has led to thousands of Oklahoma deaths and addictions.

A multitude of sales call notes from 2001 to early 2004 showed that in calls on Oklahoma doctors, Johnson & Johnson sales representatives repeatedly cited studies that their own company had funded.

Those later discredited studies purported to show Duragesic improved physical and social functioning, had demonstrated effectiveness in treating lower back pain and was less likely to be abused than many other forms of opioids.

The sales representatives also repeatedly cited emergency room admission data provided by the Drug Abuse Warning Network as showing that Duragesic had a lower addiction rate than other opioid drugs.

The FDA issued a stern warning to Johnson & Johnson in 2004 that criticized the studies and said there was a lack of evidence to back the claims.

Corporate Representative Kimberly Deem-Eshleman said her company didn’t agree with the FDA’s assessment of the studies, but agreed to pull the promotional materials it was using.

The call notes reveal that during the same sales calls where sales representatives were telling doctors that Duragesic was less subject to abuse, some doctors were telling the representatives about incidents in which the opioid patch was abused.

For example, following a September 23, 2003, sales call, Johnson & Johnson sales representative Holly Abraham reported that a Stillwater doctor had told her that “nurses were taking the old patches.”

Another doctor told a sales representative about a patient who was using more than one patch.

https://www.marketscreener.com/JOHNSON-JOHNSON-4832/news/Johnson-Johnson-Drug-company-reps-blanketed-Oklahoma-doctors-with-promotional-materials-later-de-28692313/

Epizyme files tazemetostat, seeking first okay in rare cancer

Epizyme has filed for accelerated FDA approval of tazemetostat for advanced epithelioid sarcoma (ES), a rare form of cancer with no approved drugs in the US.

The Massachusetts biotech is seeking a green light for the first-in-class EZH2 inhibitor in patients with metastatic or locally advanced ES not suitable for surgery, which can be curative in this rare type of slow-growing tumour if caught early enough.

The cancer typically starts as a single painless lump, but can quickly spread to form multiple growths and be quite aggressive by the time a patient seeks medical advice. Treatment options at the moment are surgery, radiotherapy and chemotherapy, and if approved tazemetostat would be the first targeted therapy for ES.

“We believe that tazemetostat could dramatically change the care of people with ES who have limited treatment options, which are also associated with challenging side effects,” said the biotech’s CEO Rob Bazemore earlier this year.

Analysts at Jefferies have suggested that the accelerated application based on a phase 2 trial in 62 patients – due to be reported at ASCO on 3 June – looks “approvable” given that tazemetostat’s objective response rates and duration of response seem to be better than data for other drugs used to treat sarcomas.

According to the ASCO abstract, the drug achieved an ORR of 15%, with an average duration of response of more than 12 months, and what looks like a benign side-effect profile. If the FDA concurs with that view, tazemetostat could be on the market next year, and Epizyme has committed to carrying out a global, confirmatory phase 3 trial in the latter half of the year.

ES is the first of two submissions planned for tazemetostat this year as Epizyme attempts to position its orally-active drug in a range of solid tumours and blood cancers.

Next up is a filing in the fourth quarter for third-line or later treatment of follicular lymphoma (FL), a cancer that is a much bigger opportunity than ES, particularly if Epizyme can follow through on its plan to move tazemetostat into earlier lines of treatment.

While ES is a relatively small indication – representing around $100 million in potential annual sales according to some analysts – last year Morgan Stanley suggested that approval in additional cancers could propel tazemetostat towards blockbuster sales levels.

Epizyme has trials planned for the drug in combination with Roche’s Rituxan (rituximab) for the treatment of patients with relapsed refractory FL, as well as part of a triple therapy with Rituxan and Celgene’s Revlimid (lenalidomide) – a regimen known as R2 that has just been approved as a second-line treatment for FL and other forms of indolent non-Hodgkin’s lymphoma (NHL).

Epizyme files tazemetostat, seeking first okay in rare cancer

J&J unveils early-stage prostate cancer data from Erleada at ASCO

Johnson & Johnson is hoping to expand the use of its prostate cancer drug Erleada (apalutamide) in patients with metastatic castration-sensitive prostate cancer (mCSPC) – and new data presented at ASCO sheds light on the dossier under review at the FDA for this early stage disease.

Developed by J&J’s pharma unit Janssen, Erleada is already approved in the big battle ground in prostate cancer – castration resistant metastatic disease – where its big rival is Pfizer/Astellas’ Xtandi (enzalutamide) and generics of its older drug Zytiga (abiraterone).

Data published at ASCO, and simultaneously in the New England Journal of Medicine (NEJM) showed adding Erleada to androgen deprivation therapy (ADT), compared with placebo plus ADT, significantly improved the dual primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS) in mCSPC.

The study included patients with mCSPC regardless of extent of disease or prior docetaxel treatment history.

Data show Erleada plus ADT significantly extended OS compared with placebo plus ADT, with a 33% reduction in risk of death.

It also significantly improved rPFS compared to placebo plus ADT with a 52% reduction in risk of radiographic progression or death compared to placebo plus ADT.

The two-year OS rates, after a median follow-up of 22.7 months, were 82% for Erleada plus ADT compared to 74% for placebo plus ADT.

A secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with Erleada plus ADT was also met, with a 61% risk reduction compared with placebo.

In exploratory endpoints, median time to PSA progression was more favourable following Erleada plus ADT, compared with placebo plus ADT, and prostate-specific antigen (PSA) reached undetectable levels in 68% of patients in the Erleada plus ADT arm and 29% of patients in the placebo plus ADT arm.

Erleada plus ADT, compared with placebo plus ADT, achieved a 34% risk reduction in median time to second progression-free survival (PFS2), defined as time from randomisation to either disease progression on first subsequent anticancer therapy or death, whichever occurred first.

The biggest issue safety-wise was a rash, seen in 27% of patients although investigator Dr Kim Chi said most cases were Grade 1 or 2. Overall the safety profile was consistent with previous experience of the drug, he noted.

It’s bad form to pre-judge whether the FDA will approve or not, but the response from oncologists gathered at ASCO seemed to be favourable.

And while the data has gone down well in Chicago, there are also several other phase 3 studies involving rival therapies such as Bayer’s darolutamide, Pfizer/Astellas’ Xtandi, and Takeda’s orteronel – which could provide competition even if the FDA does grant a new indication.

J&J unveils early-stage prostate cancer data from Erleada at ASCO

AstraZeneca, Merck data support PARP drug in prostate cancer

PARP, or poly (ADP-ribose) polymerase, inhibitors may have an amusing-sounding name but an increasing body of evidence suggest they could be used in a wide range of cancers as long as certain mutations are present.

PARP drugs work by interfering with cancer cells’ DNA repair system, eventually causing them to self-destruct – and AstraZeneca and Merck & Co’s Lynparza (olaparib) was the trailblazer in this drug class after first approval in ovarian cancer in 2014.

But since then the drug has gone on to be approved in breast cancer, and it looks possible that prostate cancer could be another use.

Clovis Oncology already unveiled data from the TRITON2 study at the European Society for Medical Oncology (ESMO) conference in the autumn that suggest its drug Rubraca (rucaparib) could be an option in this disease.

And the latest data from AZ and Merck & Co suggest olaparib could be a potential competitor in metastatic castration resistant prostate cancer (MCRPC) with DNA damage repair mutations.

This was a mid-stage trial that was expanded from an initial phase 1 trial to determine dose – and the study’s designers opted to include a patient arm treated with a lower 300ml dose of the drug, as well as the 400ml dose.

This was because of a regulatory update as olaparib was approved at the lower dose in ovarian cancer after it was first launched.

The strongest response rate from olaparib in TOPARP-B (54%) was seen in patients treated with a higher dose (400ml twice daily), although those on the more recently approved 300ml regime also benefited with a response rate of 39%.

But the results also suggested that response changed according to sub-groups of patients with different DNA damage repair mutations.

Expert Mary-Ellen Taplin, of the Dana Farber Cancer Institute, praised the design of the study in an analysis and was supportive of olaparib’s potential in this new indication.

But she did raise an issue about how this drug could be used in a real-life setting: selecting patients with the mutations that are most likely to respond could be tricky.

“The experience provided warns that identifying appropriate patients within routine clinical practice will be challenging and will require repeated testing,” she said.

This could prove a difficult technical challenge – but the data were well received by clinicians gathered at the conference in Chicago.

American Society of Clinical Oncology’s annual meeting in Chicago, Day 2

Just spoke with Anders Bjartell, Professor of Urological Cancer, Lund University, Sweden about the data from the TITAN trial yesterday.

As a trial investigator he’s naturally really excited about the data, and he also raised some interesting points about the future of prostate cancer research. He agreed with the comments made in the oral presentation session yesterday about the need for more accurate testing to identify which mutations are present, as this has a big impact on prognosis.

Then I had a chat with Scott Koenig, CEO of Macrogenics about the company’s new breast cancer drug margetuximab. The biotech made waves ahead of the conference with data showing a survival benefit in patients previously treated with existing cancer drugs like Herceptin.

The company aims to file with the FDA based on the progression-free survival data, and will look to confirm this with further data next year about overall survival.

Right now that data is not ready but it will be interesting to see if the PFS benefit seen in the early data from the phase 3 SOPHIA trial translates into an overall survival benefit, and what the magnitude of that benefit will be.

I will be doing more in-depth coverage of these interviews on pharmaphorum later.

2 hours ago

ASCO launches mCODE to improve e-health record compatibility

ASCO has identified a huge issue that is holding back progress in cancer care – and it’s quite a basic problem.

Getting the disparate computer systems across the U.S. and the rest of the world to share electronic health record data effectively is a major problem, said ASCO president Monica Bertagnolli.

There are 15 million people with cancer in the U.S. but many electronic health record systems use different terms to describe the same type of data, or collect data in different formats, making them incompatible.

According to ASCO this dramatically limits the ability of cancer researchers and doctors to learn from patient records, hinders care coordination, and adds to admin costs for all uses, but especially practices and patients.

Most patients assume that in these modern times it should be easy for doctors to communicate details about their disease and treatment.

But not so, according to Bertagnolli, as getting different systems to interact and read patients’ electronic records is proving to be a real challenge.

ASCO is trying to solve this problem with mCODE (Minimal Common Oncology Data Elements), a core set of data elements and recommended technical specs that it considers essential for capturing and reporting patient data, and should be captured in each patient’s electronic health record.

mCODE is a collaboration between ASCO, its wholly owned non-profit subsidiary CancerLinQ, and the Alliance for Clinical Trials in Oncology Foundation..

The standards and specs have been published online at mCODEinitiative.org.

Bertagnolli added in a question and answer session that it was her “dream” to make the system available worldwide to improve communication between oncologists on a global scale.

3 hours ago

ASCO experts noted that this and other data from immunotherapies is changing the way doctors think about patients with lung cancer.

The chances of patients surviving for extended periods of time with the disease have increased considerably.

In the past only a handful of lung cancer patients would survive past five years, but with immunotherapy around a quarter could be expected to live that long.

3 hours ago

New data unveiled at ASCO shows how Merck & Co’s Keytruda (pembrolizumab) and other immunotherapies could change the outlook for seriously ill lung cancer patients.

The latest data came from a phase 1a study, KEYNOTE – 001, which as its name suggests was one of the first cancer immunotherapy trials that began in 2011 in patients with solid tumours.

There were 550 people with advanced non-small cell lung cancer on the trial, including 101 patients who had not previously received any treatment and 449 who had received treatment previously.

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.

Higher levels of the biomarker PD-L1 predicted longest survival – in previously untreated people 29.6% with PD-L1 expression of 50% or more were alive after five years, compared with 12.6% with expression levels between one to 49%. Only 3.5% of people with expression levels below 1% were alive after five years.

Among previously treated patients, 42% had responses that lasted for a median of 16.8 months, while for those who were treatment naïve, 23% had responses that lasted for a median of 38.9 months.

3 hours ago

Another interesting point from that briefing on MONALEESA-7 – the survival data could also be important in countries carrying out health technology assessment to decide whether drugs should be available in national health systems.

ASCO expert Harold Burstein said: “Demonstration of robust survival adds to a value proposition for ribociclib and this could be helpful for health systems that measure value to decide on national access to drugs.”

Novartis looks to have gained an advantage in its battle with Pfizer and Eli Lilly in the CDK4/6 class of breast cancer drugs after its Kisqali became the first to show an overall survival benefit in a subgroup of younger patients.

Results of the phase 3 MONALEESA-7 trial found that adding Kisqali (ribociclib) to standard-of-care endocrine therapy significantly improved overall survival for premenopausal women with advanced HR-positive/HER2-negative breast cancer patients compared with endocrine therapy alone.

Data unveiled today at ASCO show the survival rate was 70% for women who took the combination therapy compared with 46% for women who received endocrine therapy only.

Women who received Kisqali lived a median 23.8 months without the disease progressing compared with 13 months for women who received placebo.

The trial was the first to focus exclusively on women under age 59 who were premenopausal and had advanced breast cancer for which they had not received prior endocrine therapy.

Investigators randomly assigned women to Kisqali or placebo and all received goserelin to suppress the oestrogen that drives the disease, and one of three other established therapies – letrozole, anastrozole, or tamoxifen.

In all, 672 women enrolled on the study and after a median follow-up of 34.6 months, 173 (26%) were still receiving the therapies, with 116 women still receiving Kisqali and 57 still receiving placebo.

Speaking at a press briefing to unveil the results, Sara Hurvitz, director of the Breast Cancer Clinical Research Program at UCLA, said that until now doctors were likely to use Kisqali, or Pfizer’s rival Ibrance (palbociclib) or Lilly’s Verzenio (abemaciclib) interchangeably.

But this could change with the survival data announced today – at least until Novartis’ rivals produce similar data, said Hurvitz.

Novartis’ data “could change the way physicians practice,” said Hurvitz at the press briefing in a question and answer session.

4 hours ago

Just came out of the morning press conference – I will have updates on new data from Novartis’ breast cancer drug Kisqali, and Merck & Co’s immunotherapy Keytruda shortly.

7 hours ago

AZ/Merck & Co reveal olaparib data in prostate cancer

Data presented yesterday at ASCO 2019 from AZ and Merck & Co suggest their PARP inhibitor olaparib could be a potential competitor in metastatic castration resistant prostate cancer (MCRPC) with DNA damage repair mutations.

8 hours ago

ASCO 2019 – Kantar takes a first look at interim TITAN data

Will Erleada take the lead in metastatic CSPC? New interim data at ASCO 2019 from the phase 3 TITAN trial supports addition of Erleada to ADT for a broad range of patients in this setting.

8 hours ago

J&J’s early-stage prostate cancer data from Erleada

Johnson & Johnson is hoping to expand the use of its prostate cancer drug Erleada (apalutamide) in patients with metastatic castration-sensitive prostate cancer (mCSPC) – and new data presented yesterday at ASCO 2019 sheds light on the dossier under review at the FDA for this early stage disease.

https://pharmaphorum.com/asco-chicago-2019

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Saturday, June 1, 2019