Tag Archive for: ADC

Advances in Small Cell Lung Cancer Research | Hope for the Future

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Advances in Small Cell Lung Cancer Research | Hope for the Future from Patient Empowerment Network on Vimeo.

What new treatments are being studied for small cell lung cancer (SCLC)? Dr. Triparna Sen, a leading researcher in the field, shares promising updates, including advances being made with LSD1 inhibitors, DDR (DNA Damage Response) inhibitors, and DLL-3 targeted therapies.

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

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Transcript:

Katherine:

Dr. Sen, you are a leading researcher in the field. What is the latest research news that you can share with us about small cell lung cancer?

Dr. Sen:

There’s a lot of great research going on in my lab and labs all across the world. I think for the first time in a very long time, we are really trying to dissect the biology of small cell.   

It has been a research in making for many years. I think we have now really come to a point where we are really trying to understand the disease. I’ll go into a little more about the questions you are trying to answer. So, one of the main questions or one  of the main things that kind of is a hurdle to getting durable treatment options is that the frontline chemotherapy and immunotherapy doesn’t work as well as they should even for the approved regimens, which is the chemotherapy and the immunotherapy.  

The patients often do not have durable benefits. Even if patients have durable benefits, it’s only in a very minority of patient population which means in only about 10 to 15 percent of the total patient population actually do have any benefit from the frontline treatment. So, the main question that we are trying to answer is that why do these patients not respond to immunotherapy and chemotherapy in the frontline.  

What are the mechanisms of resistance to chemotherapy and immunotherapy? Primary resistance, what I mean by primary resistance is that patients who never respond. The disease comes back even while they’re getting the frontline chemo. So, the primary resistance, the mechanisms. Of course, when they have acquired resistance after the maintenance regimen when they come back, why are these patients having this acquired resistance to chemotherapy and immunotherapy? Because only when we understand resistance mechanisms will we be able to then come to the combination strategies.

That’s the next area of research is that once we understand the mechanism of chemotherapy and immunotherapy resistance is then coming up with effective combination therapy. So, what should we combine with immunotherapy in order to make immunotherapy better? I’ll give you an example from the research that we did. 

So, our lab focus is, as I said, on making immunotherapy better. What we understood is that there are certain epigenetic modifiers like LSD1.  

Repressing these, repressing LSD1, with a small molecule inhibitor actually augments or benefits the response to immunotherapy. So now, we are looking at LSD1 inhibitors in combination with immunotherapy. That’s one area that we are focusing on. The second are that we published extensively on is DNA damage response inhibitors which really works in combination with immunotherapy and makes immunotherapy response better.  

Now, we are investigating that in the lab the combination strategies of combining these DNA damage response inhibitors with immunotherapy. So, combination strategies. I think always coming up with novel targets. I will mention there are many novel targets that are right now in the clinical trials actually showing really, really encouraging data.  

I’m talking about DLL3 targeted BiTEs or ADCs we have seen that are showing preliminary data. We have seen a really good really good response in patients. So, finding these targets that are very specific for small cell and that can work in these unique population of patients.  

So, DLL3 targeted agents. There are agents that target B7-H3. So, we are looking at these novel targets and where they could fit in the current therapeutic regimen. Finally, since small cell lung cancer is not a surgical disease, we have to look for other options to find biomarkers. So, liquid biopsy. Liquid biopsy, what I mean by that is understanding the disease not just from tissue but also from blood.  

There’s a lot of research that’s happening in understanding the biology of small cell from blood draws from these patients.  

So, the field of using liquid biopsy or understanding the disease from blood draws is one of the areas that many labs, including ours, are focusing on, and how we can utilize these blood samples to then monitor the disease and also understand the resistance mechanisms to various drugs. I think these are the areas that we are investigating and seems, to me, very important areas that we need to address in order to really manage small cell lung cancer.   

Katherine:

What do these advances mean for small cell lung cancer patients? Are you hopeful?  

Dr. Sen:

Oh, yes. Of course. We’re always hopeful. That’s the goal, right. The goal is to have effective therapies that work and that works for a long time. That also benefits the patients in terms of quality of life which means without very severe adverse effects.   

So, very hopeful. Because I think what was limiting us for all those years for the last 40 to 50 years is that we really did not understand the complexity of small cell lung cancer. It is a very complex disease. It is very different from non-small cell lung cancer which has these mutations that you can target drugs against. So, there are this EGFR mutations and KRAS mutations in non-small cell.  

But small cell, it’s not that. It is not a disease where we have these GATA function mutations that we can devise therapies against. It’s a very different disease. The disease is aggressive. The disease progresses fast, and it also changes its physiology very fast. So, I think for the first time, we really are trying to understand the biology. What that helps is then to come with very informed decisions about therapy.  

So, yeah, I’m very hopeful. Because I think we have now targets that we are actually seeing benefits in patients. I think the more and more we understand resistance mechanisms, we’ll also be able to manage that better.   

Katherine:

That’s very promising news. 

The Role of Antibody Drug Conjugates in Lung Cancer Care

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The Role of Antibody Drug Conjugates in Lung Cancer Care from Patient Empowerment Network on Vimeo.

What are antibody drug conjugates (ADCs)? Expert Dr. Grace Dy defines this new class of therapy and explains how ADCs work to treat lung cancer.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

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Transcript:

Katherine Banwell:

What is the role of antibody drug conjugates in lung cancer care? 

Dr. Grace Dy:

So, the antibody drug conjugates are an exciting new class of therapy. In fact, it’s been developed for decades, but we had the first antibody drug conjugate that was just approved less than a year ago in lung cancer. And that’s the drug called trastuzumab deruxtecan (Enhertu). It seems like we’re always steps behind our breast cancer colleagues. 

You know, trastuzumab deruxtecan was first developed in breast cancer patients. But hey, we also find we can have some subset of patients who will derive benefit from that. But that’s just one example. There’s plenty of antibody drug conjugates that are being developed. 

So, what are antibody drug conjugates? So, as the name implies, it’s an antibody that is attached to a drug that is actually typically chemotherapy, but you can use any other drug. Generally, it’s a chemotherapy. So, you can think of it as a targeted way of delivering chemotherapy because the antibody is very specific to a certain protein. And generally, what we try to do is look for proteins that are more expressed in cancers than in normal tissues. And you try to target that and improve the therapeutic index by using a more potent chemotherapy and potentially increase efficacy that way.

Emerging DLBCL Treatment Approaches

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Emerging DLBCL Treatment Approaches from Patient Empowerment Network on Vimeo.

What is next for DLBCL treatment? Dr. Jason Westin describes emerging DLBCL treatment approaches.

Dr. Jason Westin is the Director of Lymphoma Clinical Research in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Westin, here.

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Transcript:

Katherine:                  

Yeah. You touched upon this earlier, Dr. Westin, but aren’t there emerging DLBCL approaches the patient should know about?

Dr. Westin:                 

Yes. Thankfully, there are many, many. We could spend several hours talking about lots of new therapies coming along. So, it’s a great answer to have. It’s an embarrassment of riches that we have for lots and lots of new therapies that appear quite promising in the early development stage.

In terms of those that have actually crossed over the finished line to be approved by the FDA, we have a handful of new therapies in the past few years that have been approved. Previously, we didn’t really have very many, but now there are multiple therapies that are approved by the FDA outside of a clinical trial, that are targeted treatments.

And those include antibody drug conjugates, basically an antibody like you make against an infection. However, this antibody has a chemotherapy warhead attached to the back of it. So, effectively, it’s a heatseeking missile that finds whatever target we want it to find – in this case, cancer cells – and delivers a high dose chemotherapy right to the bad guys, not to the good guys. There are also other immune therapies that we’ve seen than can be very powerful antibodies, plus immunomodulatory drugs. And we can talk about specific names of these if we’d like.

And then, lastly, there are other oral agents that are coming along that look very promising in terms of their ability to target the cancer cells more directly than growing cells.

Lastly, there’s a very new class of therapies not yet approved, but very promising. I mentioned this before. It’s something called a bispecific antibody. Bispecific – the word bicycle meaning two wheels. Bispecific is two specific antibodies. Basically, it’s an antibody that’s grabbing onto a cancer cell and grabbing onto an immune cell. “I’d like to introduce you guys. Why don’t you guys come in proximity and see if we can have a party.”

And it’s an idea here of trying to get the cancer cell to be attacked by the immune cell simply through this close proximity that occurs. Not yet approved. Looks very promising and I think probably will be approved for multiple different lymphoma types, including large B-cell, in the coming years.

Emerging Approaches in Bladder Cancer Treatment

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Emerging Approaches in Bladder Cancer Treatment from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta of the Cleveland Clinic shares a promising update in bladder cancer treatment and research, including the benefits of patient participation in clinical trials. 

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

So, Dr. Gupta, are there emerging approaches for treating bladder cancer that patients should know about?

Dr. Gupta:                  

Yes, absolutely. I would say that the field is so rife with so many different treatment approaches and ways to offer more personalized medicine. We know, for example chemotherapy followed by surgery has been the gold standard, but we have seen data that there are certain genes in some patients’ tumors which may predict how well they will respond and potentially we could avoid a life-changing surgery like cystectomy.

And we have trials with immunotherapy adding to chemotherapy in bladder preservation approaches along with radiation. So, these are some of the new work that’s been done. Approaches to intensify the effect of BCG in newly diagnosed non-muscle invasive bladder cancer patients are also ongoing. Then, in the metastatic setting, we have so many treatment options that have become approved in the last couple of years, now the goal is, well, how to sequence the therapies best for the patient and whether in the front-line therapy we can actually get rid of chemotherapy.

Some of these antibody drug conjugates and immunotherapy combinations are proving to be very effective and the hope is that one day patients may not need chemotherapy because we have chemo-sparing regimens. So, there’s a lot going on and I think the progress has been tremendous in the past few years.                                            

Katherine:                  

Some patients may be fearful when it comes to clinical trials. So, what would you say to someone who might be hesitant to consider participating in one? 

Dr. Gupta:                  

I would say there’s a lot of misconceptions out there that going on a trial is like being a guinea pig or you get a placebo. For the most part, patients are getting active drugs whenever possible. The only time where we have placebo-controlled trials is if, for that particular setting, there is no approved treatment. But I think patients should get all the information from their doctors and the study teams about the pros and cons.

Many times, it’s about – you could do the study because the patients meet the criteria and are fit to do it and if they wait for later, they may not be eligible anymore for whatever reasons.

I always put it this way, that standard of care therapies will still be available, but studies are sometimes with a tight window and tight criteria. So, I think patients should know that all these studies that are out there are very ethical and use the best possible control arm. So that even if they don’t get that experimental drug, they still get what is the standard of care unless it is something really being compared to nothing.    

Understanding Common Bladder Cancer Treatment Side Effects

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Understanding Common Bladder Cancer Treatment Side Effects from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta of the Cleveland Clinic reviews the most common side effects of bladder cancer therapies.

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

I imagine side effects vary among patients. What side effects should someone undergoing treatment be aware of?

Dr. Gupta:                  

Yeah, and that also depends on what kind of treatment they’re getting, Katherine. So, if somebody’s getting chemotherapy, some of the usual chemotherapy related side effects.

Again, it depends on what chemotherapy they are getting, but usually it’s nausea, vomiting, peripheral neuropathy, hair loss, low count, so we try to prevent their counts from going down to prevent infection. If they’re undergoing a local therapy like BCG, they may get irritation in the bladder, something called urinary tract infections can happen, or just an inflammatory state.

Immunotherapy is not as hard as chemotherapy, any day it’s easier but it can cause some rare and infrequent side effects because the immune system can turn against other organs which can sometimes be life threatening or fatal. That could be inflammation of the lung, of the colon, of the different organs in the brain, of the thyroid gland, of muscles, of heart. It can be pretty much anything. We educate the patients accordingly for that.

And, as far as the newer antibody drug conjugates are concerned, they can cause neuropathy or low counts, hair loss. So, every treatment depending on what treatment we’re choosing has a different treatment side – related toxicity profile and we go about reducing or modifying doses as we go along treating the patient.

Current Treatment Approaches for Bladder Cancer

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Current Treatment Approaches for Bladder Cancer from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta provides an overview of available bladder cancer treatment approaches and discusses the factors that impact therapy decisions.

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

You’ve touched upon treatment options but let’s walk through the treatment approaches for bladder cancer and who they might be right for, and I’d like to start with surgery. Who would be a good candidate for surgery?

Dr. Gupta:                  

I think patients who are otherwise fit, that is, they have good performance status, don’t have a lot of cardiac or other comorbidities, are not very obese, and of course have to be fit for any major procedure are usually considered good surgical candidates. But, as far as – In terms of staging, the patients with stage I, if BCG does not work in them or immunotherapy doesn’t work, they are recommended surgery if they are good candidates.

If they are not good candidates, we then – our role as medical oncologists is to offer other systemic therapies. As far as stage II cancer is concerned, the gold standard has been chemotherapy, followed by surgery but that’s the gold standard.

It may not apply for every patient. Depending on how fit patients are. Are they – we don’t usually just go by their chronological age but how fit they are? What are their comorbidities? If surgery is going to be a big burden for them moving forward, then we do talk about radiation and chemotherapy and other bladder preservation approaches.

Katherine:                  

What about immunotherapy and targeted therapies? Who would you use those on?

Dr. Gupta:                  

Well, since the advent of immunotherapies back in 2016 they’ve really – we’ve made a lot of progress and changed the way treat bladder cancer and the overall survival has improved by leaps and bounds with all these drugs.

Immunotherapy now plays a role in different stages. It is approved for superficial or non-muscle invasive bladder cancer if, let’s say, BCG doesn’t work. In muscle invasive disease we have along with others shown that immunotherapy is safe and effective, although it is not yet FDA approved, so there is a lot of clinical trials going on to prove its superiority in combination and by itself.                                   

And, in metastatic disease or locally advanced disease immunotherapy plays a huge role for patients who have either disease recurrence after chemotherapy or are not good candidates for any chemotherapy.

I would say that immunotherapy is a very big – plays a very big role in the treatment. Unfortunately, not everybody responds to immunotherapy only about 20 to 25 percent of patients do.

 That’s why we have these other novel therapies that have been coming through, like antibody drug conjugates, namely enfortumab vedotin, sacituzumab govitecan, and targeted therapy in the form of an FGFR inhibitor was the first targeted therapy that was approved a couple of years ago for patients who have a mutation in their tumors.

That’s really personalized medicine for those patients.

Katherine:                  

Right. What about biomarker testing? Does the presence of certain biomarkers impact certain treatment options?

Dr. Gupta:                  

That’s a great question and we’re all striving to find the perfect biomarker in bladder cancer. In the past we thought that expression of PD-L1 in the tumor cells and immune cells is a marker of how well the immunotherapy will work, but we have learned over the past couple of years that biomarker has turned out to be quite useless.

We don’t really need that to guide our treatment. We’re still depending on clinical biomarkers for immunotherapy use or chemotherapy use. I would say that the biomarker question is still being looked at and eventually I would say it’s not going to be one biomarker, but a composite of several different biomarkers that we will be able to use comprehensively.