Dr. Mark Awad and Dr. Roberto Chiarle at ALKtALK
Mark Awad, MD, PhD
Clinical Director, Thoracic Oncology Treatment Center
Assistant Professor of Medicine, Harvard Medical School
I hope everyone is safe, warm, and healthy tonight. I am the Clinical Director of Thoracic Oncology at Dana Farber Cancer Institute in Boston, MA. I did Medical School at John’s Hopkins, medical residency at Mass General, and my fellowship at Dana Farber as well. Why was I interested in oncology? I have to tell you a story. When in college, my father was diagnosed with metastatic cancer (gastrointestinal stromal tumor/GIST). I was only a college student and I was not in Medical School. I know it’s a rare cancer. But, it is not ALK lung cancer. But my father’s cancer is even less common. It was very challenging to learn about this rare cancer because not a lot of information was available. There were less advocacy groups, there was much less Internet, and less patients who could connect with each other. At that time because it was rare and understudied, there were few effective therapies available. Initially, my father had surgery to remove the cancer, but the cancer kept on coming back. Then we sought out second opinions and eventually went to Memorial Sloan Kettering Cancer Center. He had participated in a number of trials and surgery, but we still were challenged with recurrence. We found out that an abnormal kinase was responsible for his tumor, similar to ALK+ driving your lung cancer. My father enrolled in the clinical trial for Kit inhibitor (a receptor tyrosine kinase inhibitor). After this, though the medication is not FDA-approved, his cancer has been under control for 15 years now! His amazing result showed me the promise of cancer research. Through study of biology, you can develop therapies to combat cancer long term. The benefit of fatherly advice and counsel helped to fuel my drive to become an oncologist and lead new research for patients. I worked as a fellow with Alice Shaw and Jeffery Engleman and saw firsthand the wonderful, dedicated physicians they are. I was inspired to use my experiences and novel research on lung cancer studies to improve therapies and immunotherapies for patients.
Roberto Chiarle, MD
Associate Professor, Harvard Medical School
Attending Hematopathologist, Department of Pathology
Children’s Hospital Boston
I am from Italy and I am a pathologist. I am a clinician but I do not directly see patients. My work involved more working with a microscope and looking at lung tissue and tumors, trying to understand the drivers for tumors with the aim of finding therapies for patients. I moved to Boston in 2012 because I wanted to develop the idea of tackling ALK tumors while in Turin, in the North-West of Italy. I did my fellowship in New York and went back to Italy and became a Professor. When I developped this idea of using immunotherapy for ALK patients, I felt I needed a bigger arena to bring this concept to the clinical world. We began the use of a cancer vaccine against ALK in mouse models. However, Turin was not equipped for this work.
Now because of Covid-19, everyone knows more about vaccines. There are vaccines based on DNA, RNA, protein and peptides. DNA-based vaccines have never really worked for cancer. So, a more sophisticated formulation was needed; we chose a peptide-based vaccine. I would not be able to do this in Italy, so I moved to Boston. I remembered I tried to talk to clinicians about ALK vaccines, however clinicians were not very responsive. They were saying there were beautiful TKIs working right now. They believed TKIs were the final solution for ALK lung cancer. But, we realized after a few years that TKIs are not the final answer; it is a fantastic answer but not the final answer. New interest in immunotherapy for ALK began with the help of the Director of Dana Faber to move a vaccine forward. He said, “you need one single, new, young investigator to help you bring this to the clinic.” So, he gave me a contact name: Marc. He was the brightest young PI for ALK lung cancer in Dana Farber. He immediately also realized that TKIs are not final, that something else was needed. Immunotherapy can be a good complimentary path to TKIs. That’s how our collaboration grew.
ALK Vaccine Questions:
Q: There are so many types of cancers. Why did you decide to focus on ALK lung cancer for the vaccine?
Dr. Awad: Some mutant cancer proteins can have normal functions in the body. For example, EGFR is normally involved in normal cell function and the mutant form of EGFR can cause lung cancer. Because a normal and a mutant both are in the body at the same time, it makes it quite tricky to attack EGFR using a vaccine because you may attack some normal human cells where EGFR is expressed. One very promising information about ALK+ lung cancer is that the ALK protein is virtually not expressed in any adult lung cells. It is unique because typically only cancer cells express this ALK protein. Hopefully your body is not tolerant to ALK protein, what I mean is that your immune system has not seen the ALK protein before. Because of this unique difference where ALK is only in cancer cells and not in normal cells, hopefully the immune system would attack cancer cells and not normal cells in the body, giving us potential minimal side effects. Having a close lab collaborator such as Roberto to demonstrate this therapy in mouse models and its success leads to a great promise for patients. Other therapies have gone into clinic with much less evidence. Of course, a mouse is not the same as a human, but we can extrapolate.
Dr. Chiarle: Differential expression exists between ALK tumors vs regular tissue that does not express ALK - that is a key point for me. A vaccine can be generated against anything, but we want to avoid a vaccine that can recognize regular cells. This way, we can generate a targeting effect and minimize side effects. That is one reason.
A second reason is because ALK tumors in general are not only found in lung cancer, they’re also found in lymphoma and other cancers as well. ALK was found in lymphoma first, the lymphoma research in the ALK field was 10 years ahead in 1994. By 2007, ALK was found in lung cancer. Clearly evident for lymphoma patients was that their immune system was spontaneously actively generating antibodies against the ALK protein mediated by T-lymphocytes. It is known that ALK was normally not expressed in our tissue and when ALK was expressed, the immune system was activated by the tumor. The ALK protein was seen by the immune system. We want to use this spontaneous immunity to help patients and boost the immune system up to a level where it can generate some activity against the tumor. Make something that is naturally occurring to attack the tumor to be beneficial for patients.
Q: Can you tell us about vaccine development? Will there be a final version of the vaccine used for the trial? Does the vaccine get improved over time?
Dr. Awad: Why is this is called a vaccine? Many people think of a vaccine as preventing disease from happening in the first place. Such as in the case of Covid-19 vaccines, it is used for people who never had a Covid-19 infection to start with. Here, we are using it a little differently. Patients already have ALK cancer. For this vaccine, we are using a small piece of the ALK protein, a peptide (protein)-based vaccine, to elicit an immune response on a skin shot. The hope is to flood the immune system with a large quantity of that peptide (pieces of the ALK protein), which will generate an immune response against it. Immune cells that were stimulated will circulate in your blood and seek out ALK pieces and attack those cells wherever they are in the body.
Q: How will you know if the vaccine is working in patients?
Dr. Awad: A trial requires funding to start. We received some funding from ALK Positive and LUNGevity Foundation and several other grant sources. The funds so far are enough to fund two dozen patients. The relatively small number may bring promising results that will fuel additional enrollment and investments. The fastest way to tell if a treatment is effective is to start with someone who has measurable disease. At the time of progression, if you switch therapies and the cancer starts to shrink again, it will make for convincing evidence that your therapy is effective. What you are given is a potent and effective therapy. Some people have asked, if they have a great response now, why can I not get the vaccine to combine with my current therapy, such as a TKI and the vaccine together? That is a great goal at the end. We cannot start by that approach. For a long time, TKIs are working very well. They can work well alone. It will be very difficult to show the long-term benefit on a newly-started TKI patient. So, the initial trial will be only for patients with disease progression. This way we can determine if the vaccine works, first. Later, we can test and add a TKI. We hope to monitor with scans primarily, but we will also monitor with ctDNA (circulating tumor DNA). We will also measure immune cells in the blood and see the response to the vaccination to look for the generation of anti-ALK T-cells.
The immune system is complicated and everyone’s immune system is different. That brings up the idea of HLA (Human Leukocyte Antigen) typing. You know blood cannot be transfused between people or you cannot just transplant organs between donors and recipients; you need to have matching donors/recipients. People’s immune systems are all different because people are exposed to different things and the immune system handles each exposure differently. Depending on each person, one immune system may chop up ALK differently and present various ALK pieces differently. Each ALK peptide was chopped out to MHC (Major Histocompatibility Complex) as indicated by their HLA type. We have been doing HLA typing in ALK patients. We are considering how to match the patient HLA for a couple of immune types. So, in time, we can match it correctly to all immune types.
Dr. Chiarle: One reason why mouse vaccines do not work in humans is because the mouse immune system is different than the human. All the discoveries that were made in mice to determine which portion of the ALK protein was immunogenic in mice was very meaningful. Because we have learned a lot from the mouse model, we use a similar system to re-identify the specific ALK peptides that are allergenic for the human immune system. We were successful in identifying the ALK peptides in the HLA haplotypes present in about half the population. We started to collaborate with a group that uses sophisticated techniques in the world to make it happen. Right now, we are trying to find ALK in other haplotypes with a goal that we can provide a vaccine for all.
Current formulation is based on peptides. With the success of the mRNA vaccine with Covid-19, you have heard of the company Moderna, who was struggling for 10 years here in Boston until Covid-19 appeared. Now, it is a great company, its popularity has skyrocketed. The mRNA vaccine could be used for cancer, however it appears to be “less good for cancer”. So, right now, the peptide-based vaccine is still the best one for cancer.
We have actually tried to combine the vaccine with Crizotinib. We initially started to work with Crizotinib, but we have jumped to combining the vaccine with Lorlatinib. So now the data is from the vaccines and Loraltinib combinations. In addition, we are pretty sure the vaccine can be combined with Alectinib. We were just limited with time and money to perform all the experiments. If the vaccine worked well with two inhibitors, then there should be no reason why it cannot work with other inhibitors too. Technically, we only have proven it in Crizotinib and Lorlatinib.
Q: How do you combine your vaccine with other immunotherapies?
Dr. Chiarle: Our vaccine works well with immune check-point therapy, specifically CKD4 antibody. This is a very important question. However, the complexity of combining various kinds of immunotherapy is a clinical question. Mice are very tolerant with triple inhibitors, however human immunotherapy in clinic may be different.
Dr. Awad: The trial itself will not be open or activated yet. We are working very hard to start within a year. We are currently working on the FDA (US) side. For any novel product, we need clearance from the FDA. The FDA is requesting a lot of documentation and safety data. We have to get enough data to move forward with clinical trials. Together with industry/corporate partnership, pieces have fallen into place. Fortunately, pharmaceutical companies with enough money and resources and the ability to get those global studies are on board to bring many of the TKIs to clinics.
The question someone asked is, “if we can develop a new vaccine within one year for Covid-19, why can we not do it for ALK?” The answer is that people power and funding is limiting. We are trying to bring to clinic as much as we can as soon as we can.
Question: What is the purpose of a phase 1 trial?
Dr. Awad: Since this will be a phase 1 trial, we want to see if it is safe for patients. We want to assess its efficacy. We want to find out about side effects such as sore arm or feeling tired. What about some low-grade side effects for the next day or so? We would not want any side effects beyond that.
There will be two strategies. One is to have the vaccine with a TKI (kinase inhibitor) you are already taking. So we would like to see, when you add the vaccine, if the cancer would start to shrink again. The other cohort or strategy is to combine the vaccine with a PD-1 immune check point inhibitor (Opdivo/Nivolumab, Keytruda/Pembrolizumab, etc). These drugs work to stimulate the body’s immune system to attack cancer. These can work well in some types of lung cancer, but we have learned that they tend to not work well in ALK+ lung cancer. The hope is that we can trigger the immune system with the vaccine so a combination can recognize ALK+ cancer and to allow the immune system to kill ALK+ cancer. In the past when ALK inhibitors were combined with immunotherapy, some combinations were safe, but other combination were pretty toxic. There were some attempts with Opdivo and Crizotinib, but that trial had to stop early because hepatitis (liver inflammation) arose. Other combinations in lung cancer had to stop early because of pneumonitis (lung inflammation). So, we want to be careful to start and not throw too many drugs together for safety concerns. We want to proceed carefully because any major toxicity can hamper the progress of our trial. We will proceed step-wise with two cohorts. We will start our work from there and adjust on the way while we learn from these initial cohorts.
Q: If you have too many participants, how would you pick patients? Is it first come, first served? How does it work?
Dr. Awad: We wish there was a spot for everyone, but in early phase trials, we have built-in pauses because this are brand new drugs and we want to be cautious in case there’s some unexpected side effect. We have staggered enrollments to be safe. We start with three patients at a time and then pause enrollment. Then, after a predetermined amount of time, we are cleared to enroll more patients. After this initial stage, we are cleared to enroll on a fast pace. Initially it will be first come-first eligible basis. For you to be eligible, you are on an ALK inhibitor looking at disease progression and have overall health that meets eligibility requirements. Once the trial is open and enrolling, we will post to let all people know. Initially, the trial will be HLA-restricted, meaning we need to determine your HLA types first. Only the patients with the correct HLA types can be enrolled. We expect about 50-60% of the general population should have the HLA types that we are looking for. We are working hard to increase the ALK vaccine to accommodate all HLA types.
Q: Where would the trial be launched or offered?
Dr. Awad: Due to funding, it will only start in the Boston area. It will be at Dana Farber, but we are collaborating with Mass General, so Mass General may open as a sub-site to the study. It is at very limited locations, but you have to start somewhere. Hopefully we can expand more as the trial continues on. If things look promising, maybe with the right industry partner, we can fuel the expansion of the trial sooner. We have been working with a smaller-sized pharmaceutical company to manufacture the vaccine.
Q: Will the vaccine work in the brain?
Dr. Awad: We don’t know. It is a great question. We want to make sure while someone is on the trial, that cancer does not flare up in some sites of the body. We have seen from other immunotherapy trial studies that some PD-1 immune therapy can reduce melanoma and immune therapy can shrink intracranial tumors. But we will not know how the vaccine will perform until it is tested.
Q: We know mice are not human and vice versa. What kind of durability in vaccine response did you see in your mice experiment?
Dr. Chiarle: Yes, a mouse is not the same as a human. In our mouse experiment, the ALK vaccine could generate ALK-specific immunity that lasted 7-8 months. Mice live about 3 years, so 8 months of immunity is pretty long with one single vaccination; it is 30-40% of a mouse’s life. Extrapolate that into human years? We are talking about 20 years. The advantage of a vaccine is that, if it works, we can just repeat vaccination anytime. Eventually we can just do a booster vaccination again and one can expect immunity to be active for several years.
Q: Will the vaccines offer different effect with different ALK variants? Will the vaccine work for various resistant tumors, even with a MET alteration?
Dr. Chiarle: The expectation is “Yes, it should work for all variants”. The peptide that we chose for the vaccine is not mutated from the various variants found in ALK. Now the field knows very well what each of the variants has and none of these variants were in the peptide that we are using. Regarding resistance to a different mechanism such as MET, the vaccine should not lose efficiency. The ALK protein is still being expressed by tumor cells even if MET changes arise. ALK is still expressed; the protein is still present.
Dr. Awad: Many folks have heard about the SPACEWALK study or even participated in this study. Since we are on the topic of resistance to inhibitors, thank you. I would like to express my gratitude. If the cancer has previously responded to a TKI but the cancer is starting to grow again, the key first step is to try to understand the mechanism of resistance. To know what is the mechanism of resistance can help guide the path for the best next line of therapy. For example, if there is another mutation in ALK, it makes sense to switch to a TKI inhibitor that can combat it. If there’s a new MET amplification, perhaps it is good to switch the therapy to one that targets MET.
In the SPACEWALK trial, patients in the United States who have developed resistance to an ALK TKI can receive a free blood next generation sequencing (NGS) to determine the ALK resistance mechanism. We just published the first cohort of 100 patients (60 with results) in Thoracic Oncology (an academic journal). This study is still enrolling patients. Please ask questions to that. Thank you for volunteering.
The mechanism to ALK resistance can be varied, the hope is that the vaccine is independent from resistance mechanisms. As long as the tumor retains ALK expression, the vaccine is still providing some protection. Someone asked, can the cancer develop resistance to the vaccine? Is this a cure? These are superb questions. We won’t know until the studies are done. Cancer is complicated. Even with some of our studies we can perform in advance, we do not know how it will be until we test it in a trial. We are already trying to prevent any potential problems that we can foresee. Our hope is that we are developing a vaccine that can overcome several known resistance mechanisms.
Colin Barton*: A plug for SPACEWALK study. Dr. Awad is now managing that project. There are two major reasons why I encourage people to participate. Being in the trial may help guide your next treatment. You will get an analysis of where your cancer is. For your next treatment, which TKI may help you better? Or, should go onto a different type of treatment? The second reason is because the results you help gather will help further research and will accelerate more research. This result may help guide researchers to develop the next set of treatments. The only requirement is you have to reside in the US and have progression on a 2nd or a 3rd generation TKI.
Q: Do you need more money, awareness, and support to boost the vaccine trial?
Dr. Chiarle: Of course, more money always helps. The main reason is that we cannot stop here. This is the beginning. If our trial result is good, companies will attract more money. We are planning ahead already. Some things in the trials are not covered by the company. We would like to find out if we can improve upon our vaccines. What is a better way to vaccinate patients to improve their immune response. We would like to expand vaccines to have more coverage. Will there be resistance to the vaccine? It is an unknown. A lot of this work is by ourselves in the lab. The speed of development is limited by money and the number of people working on the problem. Billions were invested in Covid-19 vaccine development. The FDA changed their standard procedure for the Covid-19 vaccine. A typical vaccine undergoes much scrutiny and many solid repeated experiments and trials. For the Covid-19 vaccine, it was mostly bypassed by the urgent need. However, everyone hopes that the FDA will learn from the accelerated ways, maybe increase the vaccine approval rate if still safe. Perhaps, in the future, approval for a vaccine may get faster based on urgency.
Q: There’s a lot of talk about adaptive trial design, to work with the ALK population, to work with us to take the patient’s point of view into account?
Dr. Awad: We received great feedback at each step as we received funds from the ALK Positive/LUNGevity grant. Many patients serve on the Board. We always take this feedback to heart when we are planning to launch the trial. We will share with here to incorporate as much feedback as possible and still retain rigorous trial standards to know if the trial is working.
Colin Barton*: I want to let all the members know that Dr. Awad is also a reviewer for our research selection process. On behalf of all our members, I would like to thank Dr. Awad for helping us.
Dr. Awad: I cannot say enough, “thank you everybody for your focus on research”. Everybody is affected by cancer and is going through so much already. To also dedicate time to fundraising and research, it is so meaningful. Roberto and I applied for a grant several years ago for about $750,000 from MIT. We were awarded that grant. However, unfortunately, the money was not enough to open a trial; the money was not enough to manufacture the vaccine. MIT replied, “we will keep the money safe for you until you are ready”. Skeptics out there. It was not until ALK Positive/LUNGevity gave us the grant that it pushed it over for us to open the trial. Everything is falling into place. Thank you!
Q: If everything goes well in phase1, how long will you expect phase 2 to start? How many patients in phase 2?
Dr. Awad: Our hope is phase 1 will accrue all the patients in one year. Then, we will be ready to develop more vaccine with HLA types. If we see promising results, we hope to see a snowball effect to gather more funding and manufacturing partners. We are looking at a phase 2 trial of 50-60 patients.
Q: If you see prolonged effectiveness of an ALK inhibitor with the addition of an ALK vaccine, can you get a pharmaceutical company to work with you so that patients can stay on the same treatment (TKI) longer? It will be in the pharmaceutical company’s interest to help you if adding this ALK vaccine prolongs the effectiveness of an ALK inhibitor.
Dr. Awad: We really hope so, yes.
Q: Why not do a trial with patients who have no evidence of disease (NED)?
Dr. Awad: To be in the state where you have no evidence of disease is great. However, NED can make it difficult to figure out the efficacy of our vaccine at phase 1. It is hard to find the lack of “lack of progression”. If you are doing so well, is it due to the vaccine? Or was it due to something else? So the initial trial is for patients who do have progression because the efficacy of the vaccine can be more easily determined. If that is successful, then I can see adding the vaccine to a TKI on a 1st line setting and hopefully seeing extension of benefit when compared to the TKI alone.
Dr. Chiarle: The vaccine works the best historically when the tumor is small. So, it is a battle against the immune system and a number of tumor cells. It is like two armies fighting each other. The smaller the tumor army, the higher the chances of the immune system army to kill the tumor army. Right now, the clinical trial needs to start at the point of progression because it is easy to see a result. But ideally, we would be vaccinating at minimum evidence to eradicate any residual tumor army. Even at NED, there is possibly some tumor cells that may come back after several years. That is why we want to activate the immune system because that is what the immune system does best: eradicate small numbers of foreign cells.
Q: What we understand is that ALK TKIs put cancer to sleep. If the vaccine is successful, can it actually be curative?
Dr. Chiarle: Yes, that is exactly what we see in mice. The ALK TKI can control the tumor and put the tumor to sleep. In contrast, we can cure mice! We can eradicate mouse tumors with the vaccine. That is exactly what we are going for.
Q: Would it be possible the vaccine can work by itself? Without a TKI? Or with other immunotherapy?
Dr. Chiarle: That is something we would like to find out. ALK inhibitors are a very important tool to reduce the dimensions and activity of the tumor. It is possible that the vaccine could work alone but TKIs are so good of a tool that we want to use it too! If well tolerated, reduce the time we can use the TKI to reduce tumor volume. Eventually patients can stop the TKI if vaccinated.
Q: Are you using the bloodwork from the SPACEWALK trial to ID patients with the correct HLA types?
Dr. Awad: Funding for HLA typing is a separate cost from the NGS costs. The SPACEWALK study cannot include HLA typing but it is a great idea. We are offering it to patients right now. It is not built in right now. It is being considered right now.
Q: Could this trial be used to study ALK driving cancer but not lung cancer?
Dr. Awad: Yes. Extend it to other lung cancer that is driven by other genes (such as ROS1) as well.
Dr. Chiarle: The original work was on done on lymphoma. Lymphoma works even better because it is not a solid tumor mass like in lung cancer. Being smaller, not a solid tumor, it is easier to be attacked by the immune system. We think if we get quality results in the lung space, we can expand it to other cancers. A clinical trial in lymphoma is more difficult because patients are typically children so it is more complicated to get approval to start a trial from the FDA. So, if we can find good results in the lung space, we can immediately apply it to other cancers similarly. A small fraction of colon cancer, breast cancer and sarcoma have very similar types of mutation to ALK+ lung cancer. We project this vaccine would work in many types of cancer.
Q: Are you accepting any additional funding?
Everyone/Drs: YA! Big Yes. We’ve had exceptional support from LUNGevity and the ALK Positive community for our work. Any additional funding would help us move faster.
Q: How easy is it to extend to other HLA types?
Dr. Chiarle: It should be fast. We’ve learned so many things so far. If successful, we can compress it down with all our years of experience to be translated and work in other HLA types faster. Also,if the FDA first approval was slow, then to expand it to other HLA types is much easier. Usually it is harder for the 1st approval from the FDA, later expansion will be faster.
Q: Under what circumstances can the ALK vaccine be combined with immunotherapy?
Dr. Awad: It will be under an additional cohort. Somebody who has used TKIs but still has disease progression. If someone has already been on chemotherapy before and still sees disease progression. Everything else has been tried and not worked before. Someone who needs a novel therapy, then we can offer it to them.
Q: Is a patient that has progressed after they tried Lorlatinib who you will enroll in the trial?
Dr. Awad: We have tried to build in some flexibility into the trial. For example, you have 1st line Alectinb, then you start to see progression, not immediately life threatening, so this is the time to try to add the vaccine. Or if someone is on Lorlatinib, you are starting to see scans showing progression but not an immediate change needed. Maybe this is the time to add the vaccine and we can allow this patient to join the trial.
General Questions:
Q: Why do people on Alectinib have sun sensitivity? Is it the direct heat from the sun? I am a sailor and I need to know to shield the sun.
Dr. Awad: In general, in skin cancer prevention, we recommend avoiding direct sun exposure with hats and sunscreens. Everyone’s different. Some people find no effects with sun (Alectinb/Lorlatinib). Whereas some patients do find that they are more sensitive. They might burn more easily or might feel some sensitivity to the skin. It is not clear why it happens. But whatever the reason, this phenomenon is not unique to ALK inhibitors. Certain drugs can cause rashes even with no sun exposure. Antibiotics can cause similar skin sensitivity issues. People often learn what works for them or find out what side effects they do or do not have by experience.
Q: This is a vaccine-related question but not an ALK vaccine question. With the most recent Johnson & Johnson vaccine for Covid-19 being approved, do you recommend a particular Covid-19 vaccine for lung cancer patients? Or just any Covid-19 vaccine?
Dr. Awad: It is a great question but outside of my expertise. I would say distribution is so variable and so unpredictable: state to state, center to center. We have been lobbying very hard to get lung cancer patients to be prioritized to get the vaccine. But, every state is different right now. For Massachusetts, you need to have two co-morbidities for a Covid-19 vaccine. Supply is limited right now too. I have known people who had signed up, got a slot, and then it was cancelled. Or it was very hard to get spots. More people getting vaccinated in general is better. No choice as to what vaccine to get right now. Usually you get a slot and the workers tell you what they have that day and you just take it. The Johnson & Johnson shot is effective as well. If you have the opportunity for a vaccine, just take it.
Q: If Lorlatinib becomes 1st line, as a clinician, would you use Lorlatinib as a 1st line drug or Alectinib as a 1st line drug?
Dr. Awad: This is a great question. It is subject to debate right now. There were two 1st line trials, the ALEX study, Alectinb vs Crizotinib. Where Alectinib was chosen as a 1st line drug. An ideal study is Alectinib vs Lorlatinib, however this trial is not done yet. The CROWN trial studied Lorlatinib vs Crizotinib. We know Crizotinib is not a good 1st line anymore. It is not ethical to enroll patients in that trial in the US. So, this question became a data-free zone. We don’t know. I would have to consider the side effect profile of each drug. The FDA have recommended a start of 100mg for Lorlatinib, but that is high for many patients. There will be stronger side effects. A dose of 75mg or even 50mg will be better. Lorlatinib is still very effective. Some people discuss starting Lorlatinib at 50mg. But again, no data either because that is not how the trial was designed. This is where the oncologist’s personal preference and experience comes into play. We try not to make decisions without data. We sometimes make best choices. I don’t know the exact answer, but this is up for debate.
*Colin Barton is a member of the ALK Positive Support group, and Chair of the ALK Positive Medical Committee.
You can watch the entire video here: https://www.youtube.com/watch?v=bJ9TNCw9Mq0
The questions have been organized and are not in the same order as on the video.
Compiled and transcribed by: Alice Chou