I'm Dr. Erin Schenk. I'm a medical oncologist with the University of Colorado. And I'd like to talk about some of the new immuno-oncology approaches that have been presented at ASCO.
So one of the talks that I was really interested in was presented by Dr. Luke on a biospecific antibody that binds to PD-1 as well as LAG-3. So both PD-1 and LAG-3 negatively regulate the T-cell response. And in preclinical data, it was demonstrated that when the T-cell response becomes more active, it becomes more activated if both PD-1 and LAG-3 are inhibited.
So in this phase-I clinical trial, initially, they did a dose-escalation cohort. And then after safety signals were able to be determined, they then expanded into specific patient populations. And I'll talk about the lung-cancer patient population.
So in these patients, they could either have had immunotherapy previously or be immunotherapy-naive prior to receiving this bispecific molecule. And what they saw, in terms of response, is that in 5 of the 29 patients, they saw a tumor response to the therapy. They also did some biomarker correlates on tissue analyses done pre-treatment, and what they found was responders to this biospecific antibody had LAG-3 that was detected within their pre-treatment specimen.
But the patients who responded did not need to have PD-L1 expression. In fact, some of the responders did not have any PD-L1 expression at all. So what's not reported in this presentation is whether co-expression of PD-1 in LAG-3 on the same T cell is necessary for a response.
And as this trial keeps accruing, overall, I'm very interested to see these results. Tumors use multiple means of evading the immune system, and I'm hopeful approaches like these and others will result in better outcomes for our patients, as well as rigorous biomarker testing to better understand which patients should get which therapy.
I'd like to share an interesting poster presented at the ASCO 2020 meeting. And this presentation, was on a new biomarker of response to immunotherapy. A group from Montreal-- or excuse me-- a group from the University of Montreal in Quebec demonstrated an interesting association between colonic uptake on PET scan and responsiveness to immunotherapy.
And so over the past couple of years, it's been understood that there's a connection between the diversity of the microbiome in the gut with responsiveness to immunotherapy. And the overall hypothesis is a more diverse microbiome results in a more diverse antigen presentation to the immune system, which allows for a more expanded T-cell repertoire to be activated and ready to respond to any pathogenic threat.
And so the authors had noted that previously, patients received antibiotic therapy which decreases gut-microbiome diversity results in an increased FDG uptake on the PET scan in the colon. So therefore, they looked retrospectively at patients who received immunotherapy for metastatic lung cancer and had a PET scan prior to treatment. They excluded patients who had antibiotics in the two months previous to treatment.
And so what the authors report is an association between high colon uptake of-- or excuse me-- high colon avidity on PET scan on pre-treatment PET with a decreased responsiveness and progression-free survival on immunotherapy. And furthermore, they were able to do analyses on the colon microbiome in a subset of these patients, and what they found is that patients who had this high PET uptake in their colon pre-treatment had a decrease in microbiome diversity on their testing.
So they conclude that we may be able to use the FDG avidity of the colon on PET scan pre-treatment as a surrogate for gut microbiome and as surrogate for patients who might not respond so well to immunotherapy. So what we don't know yet is if, somehow, we can change a patient's microbiome by either diet or the addition of probiotics to help increase their chances for response to immunotherapy. So I look forward to the results of continued study on this phenomenon, and hopefully, one day, be able to incorporate microbiome biomarkers into the treatment of my patients.
And finally, from ASCO 2020, I'd like to highlight some poster presentations that studied the association between the innate immune system and outcomes or side-effects for patients with lung cancer on therapy. My laboratory is very interested in the role of innate immune cells in the tumor microenvironment, and I found these two abstracts particularly interesting.
So one is the report by Dr. Ferrera and colleagues from Milan, Italy, who report on in association between neutrophils with hyperprogressive disease on immunotherapy. So they define the phenomenon of hyperprogression of disease as very rapid growth during treatment with immunotherapy. And this group sought to study whether pre-treatment differences in circulating immune cells are associated with disease hyperprogression.
So they were able to study 52 patients with lung cancer, and five of these patients experienced hyperprogression while receiving immunotherapy. So notably, they found in pre-treatment blood samples that the patients who eventually experienced hyperprogression had very high levels of immature neutrophils in the peripheral blood, and they were also to recapitulate these findings in a mouse model. And I look forward to future mechanistic studies from their animal models to better unravel the connection between neutrophil phenotypes and hyperprogression of disease.
And so finally, associations are also being found between circulating neutrophils and pulmonary changes observed when initiating brigatinib, an ALK/ROS1 inhibitor. So previously, studies using brigatinib have reported that a small subset of patients experienced early pulmonary events that often resolve either with treatment interruptions or a brief course of steroids. And at our institution, one of our medical-oncology fellows spearheaded a prospective observational study to better understand the incidence of these pulmonary events.
The patients who started on brigatinib went through a number of tests, including PFTs, a six-minute walk test, a dyspnea questionnaire, as well as blood draws at baseline and then several days after starting brigatinib. And what our fellow Terry found was pretty surprising. Nine of 10 patients enrolled demonstrated some level in reduction in DLCO with the initiation of brigatinib. And three out of those patients experienced a 20% or greater decline in DLCO.
What's really important to note is that none of these patients were symptomatic, even with these larger drops in DLCO. And all the patients that we were able to test demonstrated a resolution in those DLCO changes.
So in parallel, we performed CyTOF analysis on the patient blood draws at the different time points. And notably, these patients who had that larger DLCO drop, or that 20% or greater drop, had higher levels of activating neutrophils circulating in their peripheral blood. How these innate immune cells are connected to the decrease in DLCO is unknown. Whether or not this is a good prospective biomarker is unknown. But we continue to enroll patients in a prospective manner to try and better understand this relationship.