Imfinzi only immunomed getting 3 year survival in non-small cell lung cancer

Data presented at ASCO 2019 showed 57% of patients
alive at three years vs. 43.5% on placebo

AstraZeneca has presented three-year overall survival (OS) results from the Phase III PACIFIC trial of Imfinzi (durvalumab) in unresectable, Stage III non-small cell lung cancer (NSCLC) during the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

These latest results show a durable and sustained OS benefit in patients with unresectable, Stage III NSCLC who had not progressed following concurrent chemoradiation therapy (CRT), a previous standard-of-care (SoC) treatment. The OS rate was 57% at three years for patients receiving Imfinzi vs. 43.5% for placebo following concurrent CRT. Median OS was not yet reached with the Imfinzi arm vs. 29.1 months for placebo.

Dave Fredrickson, Executive Vice President, Oncology Business Unit said: “These findings for Imfinzi are another example of our focus on bringing long-term survival benefits to patients who still have a chance of being cured. These three-year survival results further establish the PACIFIC regimen as the standard of care for these patients, and we are optimistic this survival trend will continue as we move towards the five-year landmark in this curative-intent setting.”

Results build on the primary two-year OS analysis that was published in The New England Journal of Medicine in September 2018 and demonstrated a significant OS benefit for treatment with Imfinzi vs. placebo after CRT, regardless of PD-L1 expression. The primary analysis showed Imfinzi reduced the risk of death by 32% (HR 0.68, [99.73% CI, 0.47-0.997], p=0.0025).

With the additional year of follow up, the latest results for Imfinzi showed consistent and durable efficacy, maintaining a 31% reduction in the risk of death vs. placebo after CRT (HR 0.69, [95% CI 0.55-0.86]).

https://www.astrazeneca.com/media-centre/press-releases/2019/imfinzi-is-the-only-immunotherapy-to-demonstrate-overall-survival-at-three-years-in-unresectable-stage-iii-non-small-cell-lung-cancer02062019.html

Spectrum Has Results from 2 Phase 3 Neutropenia Med Trials at ASCO

Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with a primary focus in hematology and oncology, today announced integrated analysis results from two Phase 3 clinical trials of ROLONTIS. ROLONTIS is a long-acting granulocyte colony-stimulating factor (G-CSF) being studied as a treatment for neutropenia in patients undergoing myelosuppressive cytotoxic chemotherapy.

The analysis found that integrated efficacy and safety data from the two identically designed Phase 3 trials – ADVANCE and RECOVER – were consistent with results from the individual trials, demonstrating that ROLONTIS was non-inferior to pegfilgrastim in the reduction of duration of severe neutropenia (DSN) in all four cycles of treatment. The summary was presented today during a poster session at the American Society of Clinical Oncology 2019 Annual Meeting in Chicago.

https://apnews.com/Business%20Wire/cb5cb9beafd340968f80b8d94afa2ccf

Celgene: 4 Things To Watch for at ASCO 2019

More than 32,000 oncologists, researchers, nurses and patient advocates from around the world are expected this week for the 55^th American Society of Clinical Oncology (ASCO) Annual Meeting to learn about the latest advances in cancer research and innovations in cancer care.

With more than 2,400 abstracts accepted for presentation at the conference and more than 3,200 additional abstracts accepted for online publication, we’re highlighting four areas of research being discussed at ASCO that shouldn’t be missed.

1. Exploring CAR T Cell Therapies for Chronic Lymphocytic Leukemia and Certain Lymphomas

Some anticipated studies are focused on the development of chimeric antigen receptor (CAR) T cell therapies as oncologists are excited to learn as much as possible about this innovative therapeutic class.

Researchers will be presenting new data from Celgene-sponsored studies on the potential durability of patients’ responses to an investigational CAR T-cell therapy in patients with relapsed/refractory mantle cell lymphoma and the impact of this investigational therapy on health-related quality of life in patients with diffuse large B-cell lymphoma (DLBCL). As well, researchers will address the adverse events (AEs) of these investigational treatments observed in patients with various cancers.

Some of the cancers for which CAR T-cell therapies are being explored as potential treatments include chronic lymphocytic leukemia and relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL).

2. Targeting Janus Kinase 2 (JAK2) in Myelofibrosis

The only potential curative treatment option for myelofibrosis is a stem cell transplantation, but many patients are ineligible for the procedure. This year at ASCO researchers will present results from a study focusing on a therapy of a wholly owned subsidiary of Celgene that targets a protein called Janus Kinase 2 (JAK2).

More options are needed for these patients, and data at ASCO will reveal what is on the horizon.

3. Targeting Cereblon in Relapsed/Refractory Multiple Myeloma

Over the past decade, researchers have been working to uncover the role of cereblon in the biology and treatment of multiple myeloma. Cereblon is a protein that functions as part of the cellular machinery that disposes proteins no longer needed by the cell.

At ASCO 2019, researchers will present data from a Celgene-sponsored study on an investigational compound capable of co-opting cereblon as a mediator of the targeted protein degradation mechanism of certain target proteins. Physicians are keen to identify new treatment options since multiple myeloma is incurable and patients with the disease often cycle through multiple therapies over the course of their treatment.

4. Immunotherapy Combinations for Relapsed/Refractory Indolent Non-Hodgkin’s Lymphoma

Many patients with indolent (slow growing) NHL, such as follicular lymphoma, may experience multiple relapses that require several rounds of therapy. Their durability of response can also diminish with each line of therapy.

At this year’s ASCO, oncologists will present new analyses from ongoing Celgene-sponsored studies of a new combination regimen to treat certain types of indolent NHL.

https://www.celgene.com/asco-4-things/

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

Despina@DrSpee123

Germline testing for inherited DNA mutations is recommended for all pancreatic cancer patients!! #ASCO19 @MadameSurgeon @PanCAN@nyulangone pic.twitter.com/6oYEnzjhHx

4:50 PM – Jun 2, 2019

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

Manisha Bhattacharya@starscrapers

“In other words, cancer injustice is not a science problem, a technology problem, or a genetics problem. It is a policy problem”. Quoted by @yzafar, in the context of caring for all, especially when the problem is human-made #ASCOHealthEquity #ASCO19 pic.twitter.com/lHXJIIHwQa

6

3:02 PM – Jun 2, 2019

Zachary Moore@drzach

 · 1h

Replying to @drzach

We’re getting a much-needed history lesson now. #ASCO19

Zachary Moore@drzach

Let’s take note of which states are standing in the way of solving racial disparities in healthcare. #ASCO19 pic.twitter.com/3ojjN6jkvH

1

3:03 PM – Jun 2, 2019

Oluchi C. Ukaegbu Oke@OkeOluchi

Evidence that health policy can impact health disparities and improve access to care. Thank you @BarackObama #ASCO19 #AffordableCareActpic.twitter.com/UymLOySEuC

4

3:04 PM – Jun 2, 2019

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

Dr Riyaz Shah@DrRiyazShah

MAb topiary #ASCO19 pic.twitter.com/keigpGLWpy

6

09:08 – 2 Jun 2019

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

Javid Moslehi@CardioOncology

Current approved IO and non-IO combinations. Of course chances are pretty good that this slide will have to be revised in a week! @ASCO #ASCO19pic.twitter.com/zgCj4hhbzb

8

11:42 – 2 Jun 2019

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.

OM Ezeoke@OME_ResidentMD

At #ASCOHealthEquity session @RobinVanderpool highlights disparities in health care and #cancercare that impact outcomes in #Rural communities. @ASCO #ASCO19 #HealthEquity #RuralCareMatters #CareGapspic.twitter.com/jGQUQibpeB

7

11:13 – 2 Jun 2019

https://pharmaphorum.com/spotlight/asco-2019-live-coverage/asco-2019-day-three/