Thanks for your continued interest and support for Linnea Olson.
Linnea was able to join the weekly call on Friday! She updated us on her next steps in starting on the Turning Point 4th generation ALK drug, which will happen on Thursday! She is feeling better (no more fluid, more energy), and we have high hopes that it will prove to be effective. Stay tuned!
In our roundtable discussion:
Linnea and Kimary Kulig talked about how these targeted therapies can sometimes create deep responses rapidly.
Jeff Waldron pointed out that Turning Point was unusually responsive in making their drug available through compassionate use as quickly as they did. Linnea shared her “slip up” — bluntly saying that Turning Point was making a mistake in delaying her access, and that Colin Barton of ALK Positive was relentless in making her case for access.
Peggy Zuckerman suggested that Linnea keep a log of her experience and outcomes on the drug for herself and to share with Turning Point. Kimary Kulig offered some forms for Linnea to use.
For more, please see Linnea’s recent blog post (below) and my notes from the discussion (also below), and the session recording (20 minutes) below.
Please send positive energy Linnea’s way. Join us on Friday to see if Linnea is feeling better.
Please see the surveys Kimary Kulig shared for patient-reported progress on Slack.
Here is Linnea’s latest blog post to provide more detail on her recent news and next steps:
Drained August 5, 2021 What a busy seven days it has been. Melinda and Sally, Jemesii, Peter and his girlfriend Caroline and my brother Bink and sister John have all visited over the past week. It has been great fun, much has been accomplished and I am exhausted. However, I also have had more baseline energy. A function of restarting TNO155? Perhaps. This morning I was scheduled for installation of a PleurX-cath–financial assistance approved. My breathing has also been some improved and I went to the appointment hopeful that I should be turned away again–but this time for lack of necessity. And indeed a Pleur-x was deemed unnecessary at this juncture. Instead I had another thoracentesis which yielded 150 ml of serosanguinous fluid. Last night I learned that TPX-0131 would be at MGH no later than early next week. I know my oncologist has been working tirelessly on my behalf to forestall more delays, and my friend Rob Densen and his pals at Senator Markey’s office got involved as well. Moral of the story? Choose your oncologist’s, your friends, and their friends carefully. To put a dot on that i, I shall take my final dose of TNO155 tonight—and my final dose of lorlatinib on Sunday as I begin washout. And then, next Thursday, my lead in dose of TPX-0131. There have been moments (hours, days) in the preceding weeks where I felt I was down for the count. I don’t feel that way today. Raggedy and realistic about the fight that lies ahead, but confident that I’m going to get a shot at it. xo
Here are my notes from the weekly update discussion (beyond the information in Linnea’s blog post):
Linnea: The manufacturing and labeling delay at Turning Point was helped through the efforts of my oncologist and a number of friends.
Peggy Zuckerman: This kind of trial delay is more common and more heartbreaking than it should be. I work with a group called SWOG, which puts on clinical trials. It’s a network of doctors, and I don’t think they understand this at all. It’s a story I might use as an example.
Linnea: If you do, I know a man named Alan Lee, who was EGFR positive, rather than ALK, and there was one drug coming out that was maybe going to offer him a chance. Alan was in his early 30s. He had a toddler and a brand new baby. He died three weeks before that drug came out. We were all contacting the company and pushing them because, as you know, sometimes when these drugs work, they work quickly. Even though it sounds like it’s “last ditch”, it could turn things around.
Kimary Kulig: People don’t appreciate that these targeted therapies in particular can create deep responses very rapidly. Are you getting the Turning Point drug through a trial, or is it a single patient access?
Linnea: I use the term loosely. It’s not a trial; I’m getting it through compassionate use. They will also be opening a trial, but it’s still a trial I would be precluded from.
Brad: I recall that Jess Lin can control the dosing this way, which was a concern you had?
Linnea: Even in the trial, they would have had dose escalation, and I would have been able to go up in dose. This will stay very much the same. But she can control other parameters, to make sure that I am admitted.
Peggy: Is there an obligation in compassionate use for you to make a case study or report back to them? Reciprocity is sometimes requested by some of the companies.
Linnea: I don’t know. They would want the data. But they’re not going to throw it in their pool.
Kimary: There is not an obligation to publish, but if you have a miraculous response, they’re going to want to do a case study.
Linnea: I’m going for that miraculous response.
Peggy: I’m one of them from 17 years ago. I always say, “Follow my example.” You’re more prepared to do this than I ever was.
Jeffrey Waldron: This is pretty exceptional. The timing is frustrating, but I don’t think they were ready for clinical trials. Normally when someone gets compassionate use, the company is already in clinical trials, and they have the manufacturing up and running. I think they moved pretty quickly, given my pharma perspective.
Kimary: It’s pretty unprecedented.
Peggy: Is it a Phase 2 trial?
Linnea: Phase 1. What has been interesting though is that unlike any trial I have ever seen the mechanics of prior to a trial, there has been this dialogue going not only with my oncologist, but also with the clinical trial group at ALK Positive. Colin Barton is the head of that group, and he very persuasively and articulately pushed back against the conclusions. Months ago we had an email going back and forth, where I didn’t know that Turning Point was copied on it, so I just came right out and said, “This is not humane. And I don’t think it’s a good business decision because it’s going to make accrual more difficult — the preclusions after just three treatments.” I slipped up, but who knows, maybe it did some good. And Colin just kept on them. He used my individual case, and the case of Gina Hollenbeck, who is president of ALK Positive and also struggling. He made it frankly very personal. And that was unprecedented. I had never seen this kind of dialogue behind the scenes.
Kimary: That’s awesome. I’ve spoken to Colin before too. I think patients know, but don’t underestimate the power that you have over these companies. Your “slip up” was probably a really good wakeup call. It’s not often that pharma hears that blunt feedback directly from a patient. It was a slap.
Linnea: It called out the elephant in the room. Colin’s first response was to be aghast that I had not been more careful. But then he wrote back and said, “I see what you’re doing. You’re a genius.” Of course, I wasn’t. I just didn’t know they were in the conversation. But it’s not anything I wouldn’t say to them face-to-face.
Peggy: It’s my experience that the people who are in the lab rarely see a patient. I’ve seen a couple lab people burst into tears when they were introduced to patients because they’ve never seen the people for whom they are working. To humanize the issues and the stories and the urgency outside a weirdly clinical trial world is needed. And that is why patients should be helping to shape trials and clarify the issues from a patient’s point of view. Even a delay of 10 days vs. 12 days can be life and death.
Kimary: It certainly can be the difference between you qualifying for a trial, or not. I bring up that “performance status” measure again. That’s the biggest exclusion criterion. And even that wait time, e.g., to get your genomic test results back. In that time your health status or performance status can deteriorate and then you are no longer eligible to be on that clinical trial.
Peggy: I hear stories where somebody is supposed to have a CT scan in 30 days, but they can’t get in for one in 30 days. And rather than the principal investigator or the onsite investigator saying we’ll get you the scan at our place, or make an exception, they should build that exception into the trial in the first place. Or accommodate the patient at a different site. People drop out of trials that they would otherwise qualify for.
Kimary; If the trial is written well, there is usually a plus or minus number of days on either side.
Peggy: This is the kind of thing that the SWOG patient advocates fight for.
Linnea: A very real concern of mine is that I would still be alive, but deteriorate, as in my lung, to the point that there was nothing left to salvage. Those were conversations we were having. I know I can hold on for a long time, but let’s try to stop this progression while it can still be turned around.
Brad: So, if you start the drug on Thursday, when we meet again on Friday, what are the markers that will tell you that it is improving? Will your breathing improve? Will they do a scan?
Linnea: From personal experience, I will know by how I feel. I’m not sure when the first scan will be, and I’m also curious if they will scan before starting the drug. I’ve been on these other treatments, and I expect they will want a baseline.
Kimary: You should recommend that.
Peggy: If they have some sort of patient-reported outcome or reactions on a log, that would be valuable, for yourself and the company. For six days I was feeling better and better, then on the seventh day things slowed down.
Linnea: They’re going to be curious about what I have to say, whether or not I’m a member of the trial because I am going to be one of the first people in the world.
Kimary: That’s a really good idea. There are validated instruments, like the lung cancer symptoms scale, a dyspnea (difficulty breathing) questionnaire. If Linnea felt like it, she could fill that out.
Peggy: Maybe that’s a job she could share with a friend.
Kimary: They would be very impressed by that. They are a young company. It could really help what ALK Positive has been doing with them. You are educating them and bringing them along, and helping establish them as a company that is very patient-centric.
Linnea: It is a great idea to create my own patient-reported outcomes. I’ve never liked the ones that we are given.
Peggy: If you were the mom of a little one with lung problems, you would be tracking, monitoring, and keeping a notepad by the cribside. You’re the baby here. You can keep the log. You slept well, or you didn’t. All the things that you would monitor.
Kimary: I can float you a couple surveys. The reason I’m advocating for using some validated instruments that they are already used to is that the FDA acknowledges their validity. It could lead to them having a label claim, such as impacts dyspnea. By the time they get to their Phase 2 and 3, they will be including patient-reported outcomes questionnaires. The common ones that are used include the Lung Cancer Symptoms Scale, and a dyspnea scale that I was trying to validate with Amy Abernethy. [Please see Slack for the surveys that Kimary shared.]
Peggy: Is there any instrument that is used elsewhere out there that would be reporting daily progress, a log, not outcomes? I see too many of these surveys only capture outcomes at the end of the trial vs. the ongoing issues the patient is facing.
Brad: I was a patient advisor of a group out of Mayo that is putting mobility measurement devices on patients as another way to measure quality of life. It’s moving to continuous device-reported monitoring.
Kimary: Linnea, if you have a Fitbit or an Apple Watch, that is information they would love to have. I proposed that Verily do this — that they would have a study watch to capture an objective measure of performance status, such as being up and about. The 50% of the time ECOG cutoff is so damned subjective. [The ECOG scale was developed by the Eastern Cooperative Oncology Group (ECOG) in 1982.]
Brad: Linnea, what do you need now? How can we help? What is “done”? We were trying to help you navigate to your best next treatment, and that could be this Turning Point drug. And there are many people following your journey, and very keen on how they can help.
Linnea: It continues to move back. The next couple of weeks are critical — to see how and if I respond. I’m going to be focused on that. And that’s up to the universe. I really like this idea that was broached today about continuing to be an active participant in my role in a compassionate use situation, even if it’s not mandated. I want to use a validated tool, so it is taken seriously, and maybe add some anecdotal comments on the side if I’m feeling whimsical. It’s a good way to continue to hold the reins on the horse.