Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

One of the exciting developments in metastatic urothelial carcers of late has been the emergence of checkpoint blockade with some very encouraging signs of durable clinical activity. Urothelial cancers comprise a group of urinary tract tumours including bladder, penile, ureter etc, although most trials tend to enroll bladder cancer patients, where there is a high unmet medical need.

Chicago John Hancock Center View

View from the 95th floor of the John Hancock Center, Chicago

This year alone has seen the FDA grant AstraZeneca with breakthrough therapy designation for durvalumab in February, while Genentech/Roche subsequently received approval for atezolizumab (Tecentriq) based on phase 2 data on May 18th.

To put these developments in context, the last FDA approval in metastatic urothelial carcinoma was almost 4 decades ago in 1978 for the chemotherapy cisplatin!

As is often the case in Pharmaland, once one company starts exploring a therapy in a given tumour type, others will quickly follow. Already we have several immunotherapy agents being evaluated in urothelial carcinoma both in early and metastatic disease, so what can we learn from the data presented at ASCO last week and where is the landscape going in the future?

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Lung cancer, along with metastatic melanoma, has been very much to the forefront of attention in cancer immunotherapies with both nivolumab (Opdivo) and pembrolizumab (Keytruda) garnering approval as monotherapy from the FDA in second line treatment of NSCLC. A third molecule, atezolizumab (Tecentriq) has also been submitted to the authorities for this indication and a decision is expected soon.

Morgan Grafitti Wall

Street art in the Chicago West Loop

While no one is in any doubt that the response rates with monotherapy are low (in the 20% range) and the majority of people do not respond, the important thing so far is that when they do, they appear to be very durable responses. People are living longer, much longer than the 2–3 months of incremental improvement we are used to seeing with chemotherapy or targeted therapies.

The race is now on to see how we can improve things for the 80% of people with lung cancer who don’t respond to single agent therapy:

  • What can we do to help them?
  • Which combinations look more encouraging?
  • Should we treat beyond progression?

To answer these questions, we interviewed Dr Stephen Liu and discussed his views on some of the cancer immunotherapy combination studies presented at ASCO last week.

Dr Stephen Liu

Dr Stephen Liu at ASCO 2016

Dr Liu is a lung cancer expert at the Lombardi Cancer Centre at Georgetown University, and is actively involved in numerous clinical trials, particularly in Developmental Therapeutics.

Georgetown’s founding principle is Cura Personalis, which translates as care of the whole person. It “suggests individualized attention to the needs of others, distinct respect for unique circumstances and concerns, and an appropriate appreciation for singular gifts and insights.”

Dr Liu embodies this ideal, advocating for his patients for access to the best research advances, including genomics and clinical trials of promising agents.  At ASCO, he kindly highlighted some of the important findings from Chicago and offered context on why they matter to the field.

He told us one combination was “potentially transformative” and could be “practice changing” in lung cancer with more data.

Intrigued? To find out what these important trials are and which ones to watch out for, subscribers can log-in to read the article or you can sign-up by clicking on the Blue Box below.

We have selected five key strategic trends that are emerging that will be critical to follow, understand, and even implement if you are on the coal-face of clinical research and new product development.

ASCO16 Chicago 5We aren’t talking about financial things such as cost toxicity, or even how doctors should be paid, but meaty scientific aspects that we need to watch out for. If we are going to improve on cancer research and R&D in the future, these issues will be important.

For companies and academic researchers alike, there is much to learn from the tsunami of data that hit this week if you have a keen interest in the field and a bent for making sense of patterns out of an amorphous mass of data.

Not paying attention to evolution in clinical development can mean the difference between being in the winners circle, on the outside looking in, or falling way behind your competitors. Playing catch up is never anyone’s idea of fun in this market – oncology moves at a lightning fast pace compared to many other therapy areas.

Intrigued? To find out what these strategic trends are, subscribers can log-in to read the analysis or you can sign-up by clicking on the Blue Box below.

Chicago ArchitectureChicago – the ASCO 2016 annual meeting is in full swing. This is the third and last day of our rolling blog where we’re providing updates with top-line commentary throughout the data.

If interested, you can also check out the many updates from Day 1 and Day 2.

There’s a lot happening at ASCO today, including a presentation by Vice President Joe Biden later this morning. Allow extra time for security checks if you plan to listen to him in person, and I expect there’ll be delays to the hotel shuttle buses around Chicago as roads are closed to accommodate the VP’s motorcade.

Many people chose not to come to ASCO this year – but it’s turned out to be a great meeting. We’ve heard a lot of new data which are likely to have an impact on future clinical trial strategy, as companies look to bring new products to market in what is a competitive field, particularly in cancer immunotherapy. There are how many PD-1 checkpoints in development now?

A word of warning to the wise – not all these IO molecules are going to win – some are going to fail, some will be useful tools in various subsets and some are going to be new home runs.

If you’d like to read our coverage of Monday at ASCO 2016, you can login if already a subscriber, or you can purchase access below by clicking on the Blue Box below.

ASCO 2016 Annual MeetingChicago – at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO), two global prostate cancer experts told me that a phase 3 prostate cancer immunotherapy trial in the pre-chemotherapy setting “read out” as negative last year, but they haven’t seen the data presented at a major medical meeting, published in a journal, and to the best of my knowledge, no press release has ever been issued.

(correction: the trial failure was mentioned in a 2Q 2015 earnings press release on July 23, 2015, but no separate press release was issued in the same way one would have been for positive data. As one senior PR person told me at ASCO, only announcing it in a financial news release, “doesn’t count.”)

I have been following prostate cancer for several years and was surprised by the news (that I and others clearly missed), especially as many in the field had hoped the trial might be positive and that the lack of news was a positive. In event driven trials, a later reaching of a milestone or data read out is usually good news – it means people lived longer!

The company in question is Bristol Myers Squibb, a publicly traded global oncology company. At the ASCO 2016 annual meeting, they are presenting the results of multiple clinical trials that show promising data for checkpoint inhibitors such as nivolumab, as well as combination trials with nivolumab plus ipilimumab.

BMS appears to only want the oxygen of publicity from positive data.

BMS (NYSE: BMY) is a company that has no problem issuing press releases about “positive data” – indeed, over the last two days alone they have already issued four so far to announce encouraging activity with nivolumab and ipilimumab in various tumour types. They are not so quick, however, to issue a press release to announce negative data.

Dr Oliver Sartor, the Laborde Professor of Cancer Research in the Medicine and Urology Departments of Tulane School of Medicine in New Orleans told BSB:

Good news travels at lightning speed and bad news is never heard. This is something I learned many years ago when it comes to clinical trials.

~ Dr Oliver Sartor

On clinicaltrials.gov the phase 3 trial of iplimumab in men with advanced prostate cancer prior to chemotherapy  (NCT01057810) is simply shown as “completed” with “no study results posted” – see below:

Screen Shot 2016-06-05 at 05.03.12

Over 600 men took at 134 centres around the world took part in the Randomized, Double-Blind, Phase 3 Trial to Compare the Efficacy of Ipilimumab vs Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naïve Castration Resistant Prostate Cancer.

It is, of course, possible that BMS may have told analysts or buried the news in some financial report, but if they did I missed it (update: yes, it was in the July 23, 2015 2Q 15 financial results press release).

Dr Sartor told me:

“I think around December I heard the news via the grapevine. It’s never been presented and it has gone underground. Apparently the sponsor does not want it to see the light of day, which is not appropriate.” 

We all have negative trials and I cannot help but wonder if there was something else to the story. Was there some toxicity issues or other negative issues that were not aware of? Why is the data not being presented?

I can tell you that I have heard it is a negative trial but I’ve never seen anything in writing myself. I’ve never seen the written disclosure.”

Another global prostate cancer expert told me the same story, the trial “read out” last year and he was informed it was “negative” after ASCO 2015.

This thought leader told me that BMS have since shared no data, had not published the data at any meeting, or published the results. They were keeping the data to themselves, which did nothing to advance the field.

To clinical scientists and researchers at the ASCO annual meeting, the meeting theme of “Collective Wisdom” means sharing data about what works and what doesn’t work. Science moves forward by learning from experiments that work and those that don’t work. Often a negative result can be as important as a positive if it leads to greater understanding.

ASCO 2016 Collective WisdomThe failure of BMS to disclose the results of a phase 3 study is a disservice to all who invested their time to make the trial happen, and lack of duty of care to all the men with advanced prostate cancer who participated, not only with the hope that they would live longer, but that they would contribute to research that might help others too.

It is inexcusable for a global company such as BMS to behave this way. If the data read out last year, the data could have been presented at the ASCO GU 2016 meeting, something that BMS did at ASCO GU 2013 when they presented the failure of their phase 3 prostate cancer trial with dasatinib.

Why was the pre-docetaxel ipilimumab trial negative?

On the Novel Targets podcast recorded at ASCO 2015 last year, Dr Sartor talked about the how close the post-docetaxel trial of ipilimumab in advanced prostate cancer came to being positive… but for the inclusion of men with visceral metastases, this trial would have been positive.

The ipi pre-chemo trial did not include patients with visceral mets, leading to the hope that it might be a positive trial if those men were excluded. Sadly, those hopes did not materialise.

Dr Sartor offered his clinical perspective:

“With regard to why it was negative, one can only speculate. The poor prognosis associated with visceral disease in the post-chemotherapy trial was a post hoc analysis.

Please remember that early in the post chemotherapy trial that more men died in the ipi arm compared to the comparison arm. It is conceivable that toxicity was to blame. This can be a toxic drug for some.

It is also possible that multiple lines of therapy given post protocol treatment contributed to a dilution of a positive affect. I believe this happened in the TAK 700 trial.

The bottom line is this drug was simply not active enough, or it was too toxic, or some combination of the above. Until we see more data it is hard to know. In the absence of data being presented, one might assume that toxicity played a role.”

Researchers in the field do need to know the reasons for the failure, especially given the interest that BMS have in combining ipilimumab with other cancer immunotherapy regimens, including those that do not have a high mutational load. Simply put, the data needs to be presented and published, it is unethical to do otherwise.

Update 1.35pm. Negative Trial mentioned in 2Q 2015 earnings release on July 23, 2015 – almost a year later the data remains unpublished!

Thanks to @AndyBiotech for drawing my attention to when the negative data was announced – in the 2Q 2015 earnings press release that went out on July 23, 2015. Link

“The company announced today that two Yervoy Phase 3 trials, Study -095 in metastatic castration-resistant prostate cancer and Study -156 in newly diagnosed extensive-stage disease small cell lung cancer, did not meet their primary endpoints of overall survival versus standard of care and have been discontinued. No new safety concerns with Yervoy were identified in either study. The company will complete a full evaluation of the data and work with investigators on the future publication of the results.”

If the trial had been positive or encouraging it would no doubt have merited a press release in its own right rather than a mere mention in a finance press release.

If a global prostate cancer expert, only heard from others in December (5 months after the news was buried in a financial press release) then the company has a problem in how it communicates with the prostate cancer community.

The point of this piece remains, that almost a year later the data remains unpublished and unpresented despite several opportunities to do so at major medical meetings such as ECCO 2015, ASCO GU 2016 and ASCO 2016.

If anyone from BMS wishes to advise when the data will be published or wants to dispute the accuracy of what two global prostate cancer thought leaders told me, they are welcome to send me a comment, and I will publish any response below.

Update Jun 6 BMS Promises to Publish

Thanks to Matt Herper (@MatthewHerper) from Forbes who used his influence to obtain a response from BMS to the question of where is the data? Do read his story on Forbes (link)

The company said they have plans to submit the data for publication in Q3 2016 – which probably means they are working on it now! Publication over a year after they announced the failure of their phase 3 ipilimumab trial in advanced prostate cancer is too long and reflects a double standard. The company wouldn’t wait 18 months to publish or present the data if it were positive; the same standard should apply either way.

As cancer immunotherapy moves forward into combinations, many companies are rushing from early signs of efficacy into large phase 3 trials in order to obtain a competitive advantage, with the hope of being first in that indication or beating others who have the potential to do a similar combination trial.

Only yesterday we saw early data presented in colorectal cancer (CRC) for atezolizumab (Roche/Genentech’s anti PD-L1 monoclonal antibody) in combination with a targeted therapy, the MEK inhibitor cobimetinib. Based on 4 partial responses (PRs) in a small group of patients with microsatellite stable disease (MSS), the company have initiated a phase 3 trial.

This trial has a lot of promise and potential, but it highlights how companies are moving fast on small amounts of data. Not every phase 3 trial is going to work in cancer immunotherapy. The field can’t wait 18 months for the publication of trial results when it does. The media need to write about failed trials too and hold companies accountable. What we do shouldn’t just be about eulogising the positive and new. While we all want to offer hope, at the same time we need to offer an honest reality check to the public.

Cancer immunotherapy still has a long way to go, not every person is going to respond and not every trial is going to work.

Dr Sartor would like to see the ipilimumuab prostate cancer data presented at a major medical meeting, and not just published in a journal:

I’m hopeful that we can learn from the trial even though it was negative. Results presented in a scientific form allow researchers to better understand the data. I certainly understand the financial implications and appreciate that Wall Street needs to know about negative data. Scientist have different needs. Every experiment has value and the fact that it was negative does not mean that we will not learn from it. 

I honestly feel that the companies that run trials have an obligation to promptly report the results of both positive and negative trials in a scientific forum. 

Why not submit the data for presentation at the European Society for Medical Oncology meeting in Copenhagen in October, for example?

Medical societies have no problem accepting abstracts, they recognise that debating and discussing why a trial failed to work can be as informative as discussing why something does. Meetings such as ASCO and ESMO should not just be for reporting positive data and an echo chamber for companies to share positive news.

I hope that BMS will present the data, as well as publish it. If the data was positive it would be at ESMO or another major medical meeting.

I’d like to thank Dr Sartor for being willing to share his views. Thanks also to Matt Herper for picking up the story and shining a spotlight on the topic. We’ll update the post with a link to the presentation or publication when it eventually comes out.

Update July 8: FDA set to fine companies $10K a day for late publication of clinical trial data

As reported by STAT news on June 29, Dr Francis Collins Director of the NIH announced that the FDA is set to crack down on companies and institutions that fail to report the results of clinical trial data in a timely manner. Link to Stat News story.

“Dr. Francis Collins, the director of the National Institutes of Health, later told reporters that a proposed rule — soon to become a final rule — should help by giving the agency more “clout” to crack down on institutions, not just individual investigators, when clinical trial data isn’t reported.

“That final rule is close to appearing,” he said. When it does, “we can basically say to Harvard, ‘Sorry, we’re not giving you any dollars until this principal investigator who ran a clinical trial deposits the data.’”

He also said the Food and Drug Administration will have the ability to impose $10,000-a-day fines on companies it regulates if they don’t comply with the reporting law.”

Quote from Stat News June 29 Story: “Biden threatens funding cuts for researchers who fail to report clinical trial results.

While this blog post highlights one particular phase 3 trial prostate cancer immunotherapy trial, the bigger issue remains highly topical and is one companies, and those in PR should take note of: negative data needs to be reported in a timely manner.

Unless an exception or waiver is given by the Director of the NIH, my understanding of the current FDA regulations requires posting of the results of clinical trials to clinicaltrials.gov within 12 months of study completion. This is defined as the earlier of the estimated completion date of the trial or the actual completion date.

In practice this is not an onerous burden given the speed with which companies show they can generate presentations and publications when the data is positive!

The 12 month publication time is a statutory requirement set forth in Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801).

As of the time of writing (July 8, 2016), BMS have yet to post any data for the failed phase 3 ipilimumab prostate cancer trial on clinicaltrials.gov. If the 12 months clock starts from the July 2015 actual completion date, then they are certainly taking it to the wire and run the risk of non-compliance, and potential penalities should the FDA seek to take enforcement action.

As outlined on clinicaltrials.gov website,

“FDAAA 801 establishes penalties for Responsible Parties who fail to comply with registration or results submission requirements. Penalties include civil monetary penalties and, for federally funded studies, the withholding of grant funds.”

Whether the FDA would seek to enforce the failure of a major company to comply with FDAAA801 remains to be seen, and BMS may yet deliver depending on what the actual completion date is and when that expires.

However if I was in corporate compliance, I don’t think I would be taking it to the wire or potentially playing with fire given that timely trial reporting is now a matter of public policy that has attracted the attention of politicians and regulators.

Both Vice President Biden and Dr Collins have sent an unequivocal message recently. Companies should take note and act accordingly, otherwise somebody will be fined, if only “pour encourager les autres.”

The prospect of an FDA rule with a $10,000 a day fine for late publication should certainly focus attention, if it hasn’t done so already.

Update August 23, 2016 Trial Results Posted on ClinicalTrials.Gov

On August 17, 2016 Bristol Myers finally posted the results of their phase 3 study of ipilimimumab to treat prostate cancer in the pre-chemotherapy setting. This was updated was processed on August 22 2016 by ClinicalTrials.gov. (link to results).

The primary completion date of the trial was April 2015, which means the 12 month data reporting clock started then, and according to Dr Deborah Zarin, Director of the National of Library Medicine, from her perspective the clock stops when the results are publicly available (note: this may change when new rules/regulations are published). Publicly posting data 16 months after the primary completion date is non-compliance by Bristol Myers; they get a D grade in my book. When you see the data, however, it is perhaps not surprising they were less than enthusiastic and chose to bury the initial announcement in an “earnings call” then finally post the data without annoucement in the dog days of summer.

When men with advanced prostate cancer are seeking treatment or considering a trial, they want to know the answer to the follow questions from their doctor, “if I take [fill in the blank}”:

  • Will I live longer?
  • Will I feel better?

The answer to both questions from the failed ipilimumab phase 3 trial is unfortunately, “No.”

Of the 837 men with advanced prostate cancer who were enrolled on this phase 3 trial, 602 were randomized and 598 were treated. 199 received placebo, 399 received ipilimumab 10mg/kg IV on days 1, 22, 43 and 64.

Median overall survival was 29.73 months in the placebo arm (26.12 to 34.17) compared to 28.65 months on ipilimumab (24.48 to 32.46).

Ipilimumab OS Pre-Chemo Prostate

In other words, men receiving placebo did better. The hazard ratio was 1.11, which means they had an 11% higher risk of death if you started on ipi!  What we don’t know is if there was a subset of men who may have benefited. More data is required.

Progression free survival was slightly better on the ipi arm, with a median of 5.59 months (95% CI of 5.32 to 6.28) compared to a median of 3.81 months on placebo (95% CI of 2.76 to 4.11). We don’t know if this is statistically significant, but the favourable hazard ration of 0.67 suggests it most likely is.

Ipilimumab PFS Pre-Chemo Prostate

 

Time to subsequent non-hormonal cytotoxic chemotherapy was 10.91 months (95% CI 8.44 to 14.59 months) in the placebo arm compared to 18.04 months in the Ipi arm (15.18 to 24.80). However, this delay to chemo did not translate into a better long term outcome for the IPI arm – the gold standard in cancer is how long do you live, which was the primary endpoint of the trial.

Ipilimumab Time to Cytotoxic Chemo

Overall, the OS data looks like it was the killer. We will no doubt learn more about the possible reasons for the negative overall survival when this data is published and/or presented.

It is an ethical requirement under the Declaration of Helsinki (7th Revision) that all clinical trial data be published:

“Negative and inconclusive as well as positive results should be published or otherwise made publicly available.”

It remains a disservice to the research and medical community, as well as the men who participated in this trial, to delay publication of data. Bristol Myers have offered no valid reason why it has taken 16 months for this data to be made publicly available.

Update Sept 19: Final Rule on Submission of Clinical Trial Data Published 

Last Friday, September 16 saw the announcement of the long awaited final rule on what clinical trial data has to be supplied to clinicaltrials.gov, when it has to be provided and the penalties for non-compliance. The rule will be officially published in the Federal Register on September 21, 2016 and comes into effect in January 2017.

The final rule is extensive – it is 710 pages long, so something for lawyers and regulatory experts to get their teeth into. Here’s a link to the PDF If you want to read it.

There’s also more information on the NIH website, and an accompanying article was published in The New England Journal of Medicine (open access).

nejm-clinical-trials-reporting

Learning why some combinations work and others don’t will be important to advance the field of cancer immunotherapy forwards. I do hope that companies and researchers will actively publish in a timely manner both positive and negative data. This is the final update to this post.

View from ASCO annual meetingChicago – it’s “Plenary Sunday” at the 2016 annual meeting of the American Society for Clinical Oncology (ASCO).

Cancer immunotherapy has arrived at ASCO! Not so long ago cancer immunotherapy presentations were in small meeting rooms and had only a few attendees – at this meeting cancer immunotherapy data is being presented to thousands of attendees in large meetings rooms, including the B1 plenary hall. What a difference in the space of a few years!

Today at ASCO there are several noteworthy cancer immunotherapy presentations. We’ll be writing about them here on the blog during the day.

Part of the opportunity of coming to a meeting such as ASCO is the networking opportunities it affords.

While in Chicago I heard about a phase 3 trial from a global pharma company that failed to meet its primary endpoint last year, however, – to the best of my knowledge – there’s been no publication or presentation of the negative data that may help the field move forward. The investigators have been told “it’s a bust.”

Not to publish or present negative data is a disservice to the patients that enrolled on the trial. Many would have believed their participation would contribute to the advancement of science and medicine, and potentially benefit others.

Want to know what the trial is and the company involved? Subscribers can login to find more or you can purchase access below to read more, along with our coverage of Sunday at ASCO 2016.

Update 12.30pm. Occasionally we decide something we talk about needs to be “open access” so we’ve published a short post. It is freely available to all. Turns out the negative data from BMS was mentioned in a July 23, 2015 financial results press release. Almost a year later, the negative data has still not been presented or published.

Chicago RiverChicago – the annual meeting of the American Society for Clinical Oncology (Twitter #ASCO16) starts in earnest today, yesterday was primarily education sessions and a travel day for many.

Starting today and for tomorrow and Monday, we’ll be producing a daily rolling blog with top-line commentary around sessions we attend, experts we talk to and what captures our interest and attention at the meeting. It won’t be real-time, but schedule and wi-fi permitting, we’ll be providing updates throughout the day.

It really kills us to do a semi-live blog, but our subscribers love it – they tell us that even if they’re not at ASCO, they feel like they are with us following along remotely. We’ll of course be generating a series of posts with more in-depth coverage after the meeting when we’ve heard the data.

If you’d like to join an exclusive club of companies and individuals, you can purchase a subscription below.

As a special offer throughout ASCO 2016, if you buy a quarterly subscription and then want to upgrade to an annual subscription, all you have to do pay the difference before your quarter expires. Offer to new subscribers and new purchases only. Buying a quarter is a great way to check out what we do!

The 10 abstracts selected here are actually not in order of magnitude, preference or weight… with the lone exception #1, an incredible piece of work that was a decade in the making.

Chicago!

Chicago!

Few of these choices are in the press briefing, none are in the Plenary session – they’re often hidden gems that many will miss in the hurly burly of the data drop and noise.

They’re also 10 abstracts that I feel are worthy of highlighting with some additional commentary.

Some of the ideas here illustrate some intriguing trends that are emerging, others may have a big impact on the cancer immunotherapy space, either because of the novel concept idea, or because the data are very compelling, if you understand the science.

You can decide for yourselves – which ones would you pick and why?

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After a long lull on the targeted therapies front – outside of EGFR T790M in lung cancer – this year’s ASCO has plenty to be cheerful about with new data across multiple tumour types.  We can’t cover them all here, but more will be discussed in the Daily Live Blogs starting on Saturday.

Which drugs are going to be in roaring back after a quiet period?  Which ones will be having a more muted meeting?

ASCO16 Chicago 4For those of you who are working in the targeting therapy world, take heart, there is a future beyond cancer immunotherapy; it is not the universal panacea and will likely not cure every cancer, at least for now.

There’s still a market opportunity for targeted therapies in cancer, and as we mentioned in yesterday’s ASCO Preview, there is also potential for the combination of targeted therapies with immunotherapies, so long as the combined toxicity is manageable and doesn’t outweigh the benefits.

In this post we’re looking at a selection of targeted therapies in a variety of tumour types. There’s a lot to choose from at ASCO this year.

Here’s a few we think are worth highlighting upfront.

Subscribers can log-in to learn more or you can click on the Blue Box below to sign-up and become a member of the burgeoning BSB Community who appreciate the value of education, information and, even occasionally, infotainment…

For years we’ve followed the trials and tribulations of targeted therapies seeing many approved and quite a few disappear forlornly (and officially) off to dog drug heaven. Many more sit in no-man’s land as companies eagerly wait in a holding pattern for other trial readouts in different tumour types. Sadly, sometimes these studies don’t generate enough compelling data either. With so much competition about, there are no shortcuts or low-hanging fruit in biotech or cancer drug development any more.

ASCO16 Chicago 1

En route to Chicago and ASCO!

Then along came antibody drug conjugates (ADCs), with some encouraging results in a range of cancers in both solid tumours and hematologic malignancies that lead to the approval of several new therapies.

After that, the next big advance was immunotherapies, specifically checkpoint blockade, with encouraging single agent activity in melanoma, lung, and even urothelial bladder cancer. We’ve also seen the promise fo combining two different checkpoints such as nivolumab and ipilimumab together in metastatic melanoma, albeit with an increase in toxicities.

This is all very well and good, although the challenge remains that the majority of patients either respond to therapy and relapse, or do not respond at all, depending on the circumstances, the tumour type and the regimen. We still have a long way to go in moving the needle and creating a new paradigm shift on a broad scale.

So what happens when we start to combine modalities – such as targeted therapies with immunotherapies?

Uh-oh, I hear the distant cries of disagreement erupt…

  • Remember vemurafenib plus ipilimumab in metastatic melanoma was scuppered by severe hepatitis?
  • What about osimertinib plus durvalumab in NSCLC and the increased incidence of ILD?

Both of these statements are true, and yet… we should not assume that all mixed therapy combination approaches are doomed on the basis of a mere n of 2. What happens if some are synergistic or additive? What happens of there are hidden gems that teach us new ways of doing things rather than doing the same old thing just because it’s always been done that way?

With this in mind, I’d like to open the door on our first ASCO 2016 Preview series with a look at novel combination approaches in development that caught my eye.

What are the early hints and signals that we can learn from the data? Which companies are evaluating imaginative new ideas that may turn the tables on traditional thinking?  The ideas discussed here may well surprise a few people.

To learn more, Subscribers can log-in below or you sign up for a subscription and join the ever burgeoning BSB club of sophisticated lay people – including investors and commercial/new product development people – who can really understand and appreciate the fundamentals of cancer R&D…

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