ASCO 2022 Esophageal In-Depth Slides: MOASC Spotlight

ASCO 2022 Esophageal In-Depth Slides: MOASC Spotlight

 

ASCO 2022 Esophageal Cancer Abstracts Highlights

Abstracts of interest that were recently presented at ASCO (gastrointestinal cancers symposium) just this past summer, the first is the randomized phase 2 DANTE trial in clinical oncology. So I think all of us are aware of our non-metastatic patients, but locally advanced and, unfortunately in the US, because of lack of effective screening strategies, a lot of our patients, even if they’re at least diagnosed without stage 4 disease, they typically have a very bulky disease that needs perioperative chemotherapy (systemic therapy).

How can this impact the paradigm in a perioperative setting?

But of course, we know that first line chemotherapy (systemic therapy), where for metastatic disease, PD-1 inhibitors have made an impact. So how can this impact the paradigm in a perioperative setting? The Germans actually first are giving us some data here. This is the DANTE study in which patients are simply randomized in a one-to-one fashion, either perioperative flot chemotherapy (systemic therapy in clinical oncology studies).

 

Of course, they pretty much pioneered the use of flot, now being globally used or the same perioperative chemotherapy (systemic therapy) with the addition of the PD-L1 inhibitor atlizumab. And actually, besides having the 4 months of perioperative therapy and the PD-L1 inhibitor, they actually still continue the atlizumab for 6 more months, just following this usual paradigm of consuming biologics in the adjuvant setting in clinical oncology for a longer period of time. Will this help with disease progression?

What is the Interim Analysis, and the Primary Endpoint of the DANTE trial?

So in terms of this first interim analysis, the primary endpoint of this randomized phase 2 was progression free or disease-free survival, but they did have a built-in first interim analysis to look at pathologic complete response. For those of you who remember the initial phase 2 data for flot, it was very promising for clinical oncology.

What were the Outcomes that the Flot Data Provide?

The fact that flot did have higher pathologic, complete response rates compared to the old, older combination triplet regimen of ECF chemotherapy (adjuvant chemotherapy). So here, at least in terms of the initial data readout for these 300 patients, actually fairly large for a randomized phase 2 is you do see more down-staging.

What is so Promising in this Study For Clinical Oncology?

So definitely a lot more pathologic T zero disease. So this is very promising. More sterilization of lymph nodes. So 69 versus 54% with having the PD-L1 inhibitor added to your perioperative chemotherapy. And in conversely, you have a lot more patients who are just getting perioperative chemotherapy alone without the PD-L1 inhibitor, typically having more, still persistent locally advanced disease, YPT3 to YPT4, but in terms of another more formalizing grading in terms of pathologic regression, tumor grading there are actually several different criteria for tumor regression grading. But I think most of us who are treating these patients are familiar. At least the pathologist is telling us there’s just nothing but dead tumor cells.

What is the Pathological Complete Response and Does This Affects Disease Progression?

It’s a pathological complete response. In terms of the Mandard or Becker criteria, those are two major criteria that are out there. Usually, TGR1 A lowers the score. Equivalent to pathologic complete response. They actually had both local assessments and blinded independent central review assessment to really be more objective in terms of the pathologic grading, given this was an unblinded study, but at least when you focus on the right side of the table, looking at the central assessment, you do see that actually PD-L1 may matter here in terms of these pathological complete response rates looking at all patients, the pathological complete response rates and the central assessment doesn’t seem to be that much.

Will the Addition of Atlizumab Help Clinical Oncology?

Conversely, in the local assessment, there does seem to be more favor of adding Atlizumab in terms of pathological complete response rates. But then, as you move down in terms of increasing the PD-L1 tumor expression level, the immune checkpoint, of course, that Atlizumab is targeting.

 

You do see that then there is more of a shift in terms of pathologic, complete responses. When you have higher PD-L1 Strata getting up to CPS of 5 combined positive scoring of 5 or CPS 10 or higher, and actually here, they also had a very small proportion of patients. This is typical of but a very important molecular subgroup.

Does This Show in the Pathologic Complete Response Rates?

Those with MSI have a high disease, deficiency, mismatch, repair, a lot of frameshift mutations, and a lot of tumor antigens. We do definitely see. Very high pathologic complete response rates with adding a PD-L1 inhibitor to perioperative chemotherapy (adjuvant chemotherapy) up to 63%, but these are very small numbers, but I think the other interesting aspect of this data set is that you do also see pathologic, complete response rates, even with just perioperative chemotherapy alone.

 

This is definitely something of, I think, a measured debate right now in the gastroesophageal arena, given we actually have earlier data sets in terms of looking at older preoperative studies. So this one publication, about 3 years old now in the JCO, was actually an individual patient data meta-analysis of major preoperative and adjuvant studies, both in Europe and in Asia, in which on the left panel here, you see those patients with MSI high disease, again, a very small percentage, 121 MSI high patients versus 1400 microsatellite stable patients.

Could This Be Practice Changing in Clinical Oncology?

Again, this is consistent with my practice and, I think, what many are reserving. But these high patients actually have better prognoses compared to microlight stable diseases. In many ways, this isn’t surprising given that this was a story that, in stage two, colon cancer (gastric cancer) has existed for quite some time.

What was Provocative About This Post-hoc Meta-Analysis?

And now we actually have a better explanation given the high tumor Neoantigen burden of these tumors. Likely there’s better tumor immune surveillance. But what was really provocative about this post-hoc? Meta-analysis is that for those patients who were MSI high and exposed to chemotherapy, whether it’s adjuvant (chemotherapy) or perioperative, their prognosis was actually worse than if they just had surgery alone without perioperative therapy.

 

Or surgery without randomization, adjuvant chemotherapy, versus of course, the standard of care for microsatellite stable tumors as pure chemotherapy can be clinically meaningful improvement for your long-term survival outcomes. So this is an area where there’s been some discussion within the cooperative groups.

How Else Can We Approach These MSI-high Patients Treated in Clinical Oncology?

So maybe trying to look at this prospectively formally, though, there definitely has been some emerging essentially approach in terms of just doing surgery alone for these MSI high patients and myself. I actually do check for MSI status in all my recyclable patients. But in terms of how else can we approach these MSI-high patients?

 

Given we know they’re in the metastatic setting, they are very responsive to immune checkpoint inhibitors. We do actually have data again out of Germany, but this was at the GI ASCO (gastrointestinal cancers) symposium earlier this year in January. This was a phase 2 single-arm study conducted by the German groups in which they took MSI high patients about this was about 30 actually close to 40 patients treated here in which they just simply gave them no (adjuvant) chemotherapy, but gave them neoadjuvant, dual immune checkpoint, inhibitor treatment both nivolumab and CTLA-4 inhibition with Ipilimumab and hereafter they received 12 weeks of dual immune checkpoint inhibitor therapy, they subsequently, still went on to surgery as the standard of care. And then, after recovering from surgery, they just went on to adjuvant (chemotherapy) PD-1 Nivolumab as a single agent, so no chemotherapy here, and they subsequently followed these patients looking for clinically meaningful improvement.

 

So what was very interesting and provocative about this data set, and this seems to be in line with also, I think, the rectal cancer (gastrointestinal cancers) data that made a splash in ASCO (gastrointestinal cancers symposium) and different public news outlets, is that we do see very high pathological, complete response rates without chemotherapy, just using immune checkpoint inhibitor though, in this case, this a dual immune checkpoint inhibition of 59% of patients treated had pathologic complete responses, though. I think the fact that you do still see tumors with residual pathologic disease is still viable tumor cells. There’s still definitely a population of MSI-high gastric cancer (esophageal cancers) that are just still cold, to begin with. They don’t respond to immune check one inhibitors, so really will need more data to hopefully better inform us how we can approach these patients.

What Optimal Treatment Landscape in These Trials?

What is really the optimal treatment here, whether it’s still preoperative therapy, but at least one aspect that hopefully, we’ll get some more? Is that actually we have phase three studies ongoing in the live setting, adding immune checkpoint inhibitors once such major trials, the KEYNOTE-585 study, there are actually completed enrollment over a year ago. Now we’re just waiting for data to read out. This was simply looking at perioperative chemotherapy and placebo-controlled adding either the PD-1 inhibitor pembrolizumab or placebo here, they actually gave the physician’s choice of doublet (adjuvant) chemotherapy or flot chemotherapy, but then we also have another similar phase 3 study, the MATTERHORN.

 

This actually is nearly completed to accrual, if not completed an accrual as of now. But this is also perioperative chemotherapy. They’ll hear all the patients are getting FLA chemotherapy, but the randomization here is either placebo or the PD-L1 inhibitor Durvalumab. So hopefully, we’ll see what these data sets and hopefully, they’ll pull out the MSI-high patients to see if we can still utilize chemotherapy plus immune check inhibition. At least my bias is that, at least in the metastatic.

 

We don’t necessarily have to move away from chemotherapy completely for our MSI high molecular subgroups. And then here, I just wanted to take a moment. It was good for the trainees. To just look at the different PD-L1 scoring methodologies given. I think these days, there may even still be some confusion looking at the different enumeration methods for looking at PD-L1 expression.

 

You mentioned that the DANTES trial looked at the CPS or combined positive score, and this is different than the tumor proportion score or tumor cell enumeration. That really was first born out in lung cancer in which PD-L1 inhibitors first had a biomarker linked to the efficacy of an immune checkpoint inhibitor.

What’s the Immune Compartment That’s Important in the Tumor Immune Microenvironment?

And then again, what distinguishes CPS from TPS is that you’re also counting the immune cells. Really you wanna look at what’s this immune compartment that’s very important in the tumor immune microenvironment? So hence this distinction with CPS TPS and immune cells, I still see a lot of patients for second opinions in which they do get PD-L1 testing, but then sometimes they may only be the tumor cell enumeration that they have undergone.

 

They haven’t necessarily undergone the combined cause of scoring methodology. And think this is important to help us look at some new data. So CheckMate 640 was, of course, reported last year on actually published in the New England Journal of Medicine. And we actually do have a new FDA approval.

 

Then this is squamous cell esophageal cancer (gastric cancer) specifically. So this is independent of (esophageal) adenocarcinomas, though. This was a very large phase 3 study, purely looking at squamous cell histology of over 900 patients. But this was three arms in terms of newly diagnosed stage 4 disease. PD-L1 actually overexpression was not a selection criterion.

 

Looking at TPS or tumor cell PD-L1 expression was a stratification factor at a pretty low 1% cutoff, but here patients will be randomized in a one-to-one fashion to either control arm chemotherapy here using platinum 5 of you doublet it very standard in terms of global first line treatment for these patients or open label edition of the PD-1 inhibitor Nivolumab, or actually there was a chemo free arm.

 

Relatively high dose Nivolumab and low dose Ipilimumab in which those who treat melanoma may know some of the distinctions between low dose NIVO versus high dose IPI. But here, the focus was on trying to leverage a more favorable side effect profile, hopefully with the lower dose of Ipilimumab with the higher dose of Nivolumab, and the primary endpoint was a co-primary endpoint of (median) overall survival.

 

And progression-free survival looking specifically at those. Patients in which there are tumors at least had a TPS of one or higher, but then there were key secondary endpoints in terms of hierarchical, physical testing, looking at (median) overall survival and progression-free viral and all randomized patients.

 

Because again, in this phase 3 study, there was no selection for PD-L1 overexpression. So there, this was a positive study. We have FDA approval actually for Nivolumab, and Ipilimumab, as well as a Nivolumab, added to chemotherapy. Now for the first line, squamous cell stage 4 disease.

 

But at least at this update at ASCO (gastrointestinal cancers symposium), they did give some more subgroup analysis breaking down in terms of TPS versus CPS. And what on the left panel here in terms of Nivolumab with chemotherapy versus chemotherapy, is that definitely if you at least have a TPS of 1% or higher you clearly have benefit though, the small or the percentage of the patients in which the TPS was less than 1%, really the benefit is, maybe have some question here in terms of the survival overall, survival endpoint, but in terms of CPS what’s interesting is that this is also what distinguishes TPS from CPS.

 

In terms of patients who have no PD-L1 expression in their tumor biopsy, not as even a single immune cell, it’s definitely a much lower proportion of patients. You’re looking at 51 patients who are PD-L1 CPS completely negative versus 329 patients who are only counting tumor cells. They’re considered PD-L1 negative.

 

So again, counting the immune cells is also important here, but then I think what’s also interesting here is that if you have a CPS of even just 1% across STRATA, what are they looking at? Greater than equal to 1, greater equal to 5, or greater equal to 10. There is that benefit across the board in terms of adding Nivolumab to first line chemotherapy.

Would You Wait for The Results to Consider Adding a PD-1 inhibitor For the First Line Chemotherapy, at Least for Esophageal Squamous Cell Carcinoma?

And given the fact that it may only be 10%, at least in this study population that were PDL and CPS again, completely negative or CPS zero. Do you want to wait for those results to consider adding a PD-1 inhibitor to your first line chemotherapy, at least for esophageal squamous cell carcinoma?

 

And to be honest, for esophageal squamous cell carcinoma, given their epidemiology, the risk factors, being more mutagenic still tobacco smoke exposure, similar to squamous cell cancers (gastric cancer) of the lung. Typically these are higher tumor mutational burdens, which I think again, they’ll benefit from a PD-1 inhibitor in first line treatment.

 

Conversely, when you look at Nivolumab and Ipilimumab without chemotherapy, I think there maybe you have to have more discretion here in terms of if you want to give a chemo-free regimen to your patient with newly diagnosed metastatic squamous esophagus cancer (gastric cancer). Here you do see PDL and CPS, maybe, being more favorable at higher cutoffs, though.

 

Then if they’re less than 5 between 0 and 4, there may be more debate about the degree of the magnitude of overall survival benefit, though. The caution is these are exploratory post-hoc analyses, but I think the other thing for me, in terms of trying to decipher that patient with squamous cell cancer of the esophagus (or gastric cancer).

 

Whether to give chemotherapy plus Nivolumab or doublet dual immune check one inhibition without any chemotherapy is the progression free survival data here. So this again was originally presented last year. When you look at least those patients in which the tumor cell PD-L1 is 1% or higher, at least, unfortunately, the progression free survival (overall survival)was equivalent with both arms chemotherapy versus new plus Ipilimumab, but then when you add in all randomized patients, you’re also adding in those with PD-1 CPS of 0 you really do see the progression free survival (overall survival), maybe being a less favorable meeting of 2.9 months versus 5.6 months versus with chemotherapy.

 

So I think if you have that newly diagnosed patient, very symptomatic, high disease burden. If there are no major contraindications to chemotherapy, if a patient has indications to any therapy may be best supportive care needs to be considered. But I think chemotherapy plus PD-1 is usually what I would reach for my newly diagnosed patient.

Can we interchange our different PD-L1 assays?

And then one other abstract kind of looking at the immuno-oncology data sets here. This was just a poster presentation at ASCO (American Society of Clinical Oncology) recently, but it did generate some press coverage is the fact of. Can we interchange our different PD-L1 assays? So we have 22C3, which is what the staining antibody for PD-L1 and many other Pembrolizumab studies.

 

But then you also have 28-8, which is the antibody for Nivolumab and all across all their phase 3 studies and what this single center out of Singapore this group led by Raghav Sundar and colleagues. They took 344 gastric (esophageal) adenocarcinoma patients. And what they interestingly found generated some discussions.

 

It does appear that depending on the choice of an assay that you pick, if you use 22C3, you’re probably gonna more likely to find patients to be PD-L1 negative. You’re looking at that CPS 1 cutoff versus 28-8, typically to finding a higher proportion of patients, up to 70% of patients, at least being PDL and CPS 1 or higher.

 

And if you look at the 5 cutoff, which again was a major primary endpoint for (esophageal) adenocarcinoma and gastric cancer (gastrointestinal cancers), you have 30% of patients being at least CPS 5 or higher if you use 28-8. Versus only 13% of patients. If you use 22C3, so at least for myself, I do, try and see if there’s any way of getting 28-8 to really not have false negatives miss those patients who are PD-L1 positive, but if I’m left with 22C3 or some other standing antibody assay, Maybe try and skew it in a sense given when, at least in the bottom panel here the Singapore group showed that as a continuous variable, you typically have higher scores for 28-8 versus 22C3.

New Molecular Targets in Gastroesophageal Adenocarcinoma Cancer (Esophageal Cancer)

So then, switching gears to new molecular targets that I would say are emerging and of promise in gastroesophageal adenocarcinoma cancer (gastrointestinal cancers). These were just two trials in progress, poster presentations at the recent ASCO (American Society of Clinical Oncology) meeting. FORTITUDE-101 and FORTITUDE-102 . This is looking at this new monoclonal antibody called Bemarituzumab. It’s specifically targeting the fibroblast growth factor receptor 2 (FGFR2) or of FGFR2 target here these two parallel sister studies.

 

One is taking newly metastatic patients, on central laboratory assay being FGFR2 positive, randomizing them to actually control chemotherapy or control chemotherapy plus Bemarituzumab. But then, the other study, in which actually there are several Southern California cancer centers, including UC Irvine, has this study open.

 

So consider this study for your nearly diagnosed patients is. Randomizing the FGFR2 positive patients to control of chemotherapy plus Nivolumab or chemotherapy plus Nivolumab plus Bemarituzumab. And so, given the fact that the combination triplicate combination hasn’t really been looked at yet, there was an initial phase one lead in 1 actually just recently finished enrolling.

 

Phase 3 will now be opening up, and hopefully, this will be a new changing paradigm. And the reason for this is that there was very promising randomized phase 2 data initially presented at GI ASCO (American Society of Clinical Oncology) last year. The FIGHT trial was looking at patients again with FGFR2 positive disease.

 

FGFR2, as another receptor tyrosine kinase, has been recognized as being a prognostic biomarker. Typically those patients are gene amplified for FGFR2. So similar to how you can have HER2 BGM amplified. But FGFR2 can also be gene amplified. And typically, they respond more poorly to chemotherapy, but this study didn’t only look at just FGFR2 gene amplification.

 

And here, they actually looked at patients who are FGFR2 gene amplified by circulating tumor DNA. But they also looked at protein overexpression by a. A central laboratory assay looking for specifically FGFR2B splice isoform of the FGFR2 gene product given that’s what, Bemarituzumab specifically targets, but in this study about 150 patients, one to one randomization, but it was a doubled blinded looking at progression free survival (overall survival), primary endpoint.

 

And as I mentioned, selecting patients for IHC protein overexpression or gene application by circulating tumor DNA. And if anything, what in terms of the population that screen positive for the biomarker, this is about a third currently of all comers with stage 4 newly diagnosed metastatic disease is the majority of patients are protein positive without gene application by circulating tumor DNA.

 

So this actually seems to be a bit of a divergence versus HER2. When you think of HER2, the high protein expressing patient. If you do the FISH, or of course, if you do IC2 plus, you have to do the FISH. To distinguish HER2 positive versus negative disease.

 

Typically the gene is amplified in HER2-positive diseases. So here, there may be a divergence, maybe post-transcriptional, post-translational mechanisms. This is worthy of further investigation given the fact that we do have these at least randomized phase 2 study results, showing very promising media overall survival outcomes.

 

So in the intent to treat a population that took any percentage. As long as they were IC2 plus or 3 plus for the FGFR2B protein median rival was 13.5 months with just a control arm up to 19.2 months with the addition of the Bemarituzumab through frontline chemotherapy.

 

But then there definitely does seem to be a target expression, dose-response relationship here, given the fact that you see those patients with very high levels of the protein, at least 10% of the tumor cells having FGFR2 either strong or intense staining by immunohistochemistry.

 

Now your meteor survival is, stretching out to 25 months, which is quite dramatic for first-line stage 4 gastric adenocarcinoma, for those of us, I think, who treat these patients, but in terms of other emerging targets actually one other, which I think is good to keep an eye on is this cloud and 18.2.

 

So Claudin18.2, I think it’s unique. This is actually a tight junction protein. This is not a classic receptor tyrosine kinases. We talked about the entry of R2, and of course, HER2 has been a long-term bio-action biomarker. But what we do see with Claudin18.2, at least our current understanding of it, is that this is a tight junction protein.

 

But of course, with tumor cells, having dysregulated growth, loss of cellular adhesion, you actually have repolarization of protein, too, that more ale surface and as such, there is a normal expression of clotting Heme 0.2 in the GI tract in terms of, again, it’s physiologic function as a tight junction protein, but then in tumor cells, there’s been quite a few retrospectives pathologic data sets in which you do see that different cancer, including gastroesophageal (ge) (gastric cancer) junction tumors.

 

Even in mucinous ovarian adenocarcinomas that this protein is more highly overexpressed in tumor cells versus normal tissue. So as such there, there are actually strategies to leverage, trying to target more. Differential expression of Claudin 18.2 versus normal tissue.

 

And actually, this was an oral abstract at just this past ASCO (American Society of Clinical Oncology), but there was actually even earlier phase one inner analysis data. The prior year ESMO, which actually has been published in Nature Medicine using cellular therapy, is a CAR T product of one of the first for solid tumors, but then definitely one of the first for gastroesophageal cancers.

 

So these were patients at least known to be at least some degree of Claudin 18.2 overexpression. This CT041 is a CAR T product that is pretty standard in terms of its molecular makeup and reengineering in terms of the patient’s immune cells after you collect them via luciferase.

What Was the Criteria the Patients Had to Meet?

But in terms of the study results so, this was 14 patients specifically. These are patients, typically with very poor prognosis refractory to at least 2 or more lines of therapy. But this initial phase 1 B result was all from Chinese centers. But patients receive anywhere from 250 million up to 375 million cells in terms of this initial dataset.

 

And actually, if they had stable disease and still had good tolerance to therapy, they actually could have more than one infusion. So there are even some patients who receive two repeated infusions of the CAR T product. But in terms of toxicities, I think this is pretty standard for cellular therapy products.

 

There’s definitely in terms of a lot of logistics in terms of, again, luciferase and reengineering the product, waiting for the product to be ready, you have to bridge the patients with chemotherapy, and hopefully, they have some disease stability in order to get the product when it’s ready.

What About Cytokine Release Syndrome?

But at least what was interesting to see in terms of this dosing of 250 million to 375 million CAR T-cells is that cytokine release syndrome was actually fairly modest versus what we may sometimes see with current FDA-approved CAR-Ts for hematologic malignancies, so most CRS was grade 1 to 2.

 

There was only one patient that had grade 3 CRS requiring Tocilizumab. So if anything, the ongoing phase one study is continuing to escalate the dose. Now they’re looking at even 600 million cells, and part of that is in the Nature Medicine publication, there was possibly a cellular dose to the persistence of the CAR T data, and this certainly needs to be explored further.

 

But in terms of other toxicities, very common in terms of hematologic from the lymphoma bleeding chemotherapy, again, for the patients to be able to receive the CAR T product, have their bone marrow be receptive of these re-engineered cells, even though it’s an, autologous product. But really, what’s of interest in the gastro-solved geo community is the efficacy for this poor prognosis population.

 

So at least in terms of data cut off in December of last year, you do see the response rate here is 57%, again, quite dramatic. When you think of what’s FDA approved in third-line treatment, there’s TAS-102, which is only a 4% response rate in third-line treatment, though. 

 

We do have FDA approval because it’s still better than a placebo, but this is really an unmet need. So this is very promising data, even though a small number of patients. But this study is continuing to expand. The disease control rate was close to 80%. Progression free survival was still fairly modest, though. Meaning progression free survival of 5.6 months.

What’s the Media (Overall) Survival with TAS-102?

Meaning loss survival was 10.8 months. But again, do you think of what’s the media survival with TAS-102? It’s maybe 6 months. In terms of continuing to escalate the CAR T amount of cells being given, hopefully, we’ll see more persistence to the CAR T cells really stretch out the durability of responses among high response rates.

 

Initially,  but in terms of targeting Claudin18.2, we’re not just relying on CAR T therapy. If anything, we do have a monoclonal antibody that’s of promise being looked at. This is Z,IMA, formally known as iMAP 362. This is an IgG1 specific antibody because again different than Bemarituzumab is different than Trastuzumab.

 

You’re not inhibiting any downstream signaling. If anything, you’re relying on recruitment of the immune response, antibody-dependent, cytotoxicity complement dependent cytotoxicity. But here, we actually have data with a combination of chemotherapy in the first line setting.

 

This was actually presented to ASCO (American Society of Clinical Oncology) close to 5 years ago now. But that subsequently has been published in oncology in which this randomized phase three study all German Centers (oncology), but newly diagnosed patients using an older (adjuvant) chemotherapy combination triplet of epirubicin oxaliplatin capecitabine but still very much the standard of care in terms of platinum floor pruning, at least doublet.

 

But these are patients who at least had 40% of their tumor cells having this Claudin18.2 biomarker bio central lab immunohistochemistry chemistry, and patients were there actually were looking at a higher dose, but the higher dose actually didn’t really seem to show much efficacy but had more toxicity, but at least with the standard dosing, there was a very compelling randomized phase 2 results for growth progression free and overall travel.

 

At least focusing on those patients, not just using a 40% cut. But at least 70% of the tumor cells have either moderate or strong staining for Claudin18.2. So here is a very compelling, medium progression, free survival, 5.6 up to 7.2 months, media oral survival from 9 months up to 16.7 months.

Is This Typical In Lauren Diffuse Subtype Gastric Carcinomas?

And if anything, 9 months may be points to even Claudin18.2 overexpression being a poor prognostic marker. But I think the other, at least aspect to me, that’s intriguing about this biomarker. Is it’s typically more found in Lauren diffuse subtype gastric carcinomas? This is a flip of, typically HER2, you think of the intestinal subtype.

 

And then, when we look at the large sequencing databases that are out there, like The Cancer Genome Atlas, the TCGA typically Lauren diffuse subtype tumors at the DNA sequencing level are very silent in terms of mutations and very low tumor mutational burden. Not a lot of actionable biomarkers.

 

So the fact that we have this protein biomarker that may be actionable, hopefully can change the prognosis for, typically when we think of, again, Signet ring cell adenocarcinomas (SRCCs) poor prognosis, we can make an impact on our patients. So if anything, we will hopefully have more data coming out soon.

What are Your Hopes for Median Follow Up For Clinicians of Oncology in Gastrointestinal Cancers?

This was a randomized phase 3 first line study adding Zolbetuximab or placebo control, two frontline FOLFOX chemotherapy. These were patients that were highly overexpressed for Claudin18.2, at least 75% of the tumor cells. Enrollment actually completed almost two years ago now. And now we’re just waiting for further (median) follow up to hopefully have a data readout.

 

And so, if this is a positive study, I think Claudin18.2 should be an actionable biomarker that we start testing for our patients. And then with that appreciate your attention. Happy to address any questions.

 

Joseph Chao, MD – ASCO 2022 Esophageal Cancer Question & Answer

https://oncologytube.com/v/41310

Joseph Chao, MD – About The Author, Credentials, and Affiliations

Joseph Chao, MD, one of Pasadena magazine’s “Top Doctors” for oncology since 2011, joined City of Hope as a resident of oncology in 2007 and was appointed as an assistant professor with specialty in stomach and esophageal (gastric cancer) malignancies in 2010.

 

Currently, he is heading clinical trial efforts to find novel therapeutics for gastroesophageal malignancies and undertaking studies to gain a better understanding of intratumoral heterogeneity in this illness.

 

The NIH Paul Calabresi Career Creation Award in Clinical Oncology recognizes his ongoing work in immunotherapeutics and the development of new biomarkers for gastric cancer.

 

Dr. Chao serves on the National Comprehensive Cancer Network (NCCN) panels for Gastric and Esophageal Cancer(s) and is the current academic co-chair for Elsevier/Via Oncology Pathways in gastroesophageal malignancies in clinical oncology.

 

His knowledge has helped develop national treatment guidelines. Dr. Chao received his medical degree from the University of Illinois at Chicago before continuing his education at Harbor-UCLA Medical Center.