Welcome to the ADC's Therapeutics Conference Call to review the long curve Phase II and Phase III combination clinical trial data presented at EHA today. Currently, all participants are in listen only mode. There will be a question and answer session at the end of this call. I would like now to turn the call over to Amanda Hamilton, Investor Relations at ADC Therapeutics. Please proceed.
Good morning, and welcome to our call. Earlier this morning, we issued a press release with new clinical data for longasuximabteserin, or Lonca, which is now available on the virtual 25th Congress of the European Hematology Association, or EHA-twenty 5 website. This release as well as the slides we will present today are available on the Investors section of our website at www.adctherapeutics.com. A replay of today's call will also be made available on our website. After our prepared remarks, we will open the call for Q and A.
As a reminder, during today's call, we will be making forward looking statements regarding our financial outlook. On Slide 2 of today's presentation, you can find our legal disclosures. With that, I will turn the call over to Chris Martin, ADC Therapeutics' Chief Executive Officer. Operator, please go to Slide 3.
Thank you, Amanda. Good morning, everyone, and thank you for joining us. It's my pleasure to speak with you today and to provide an update of our significant progress at OTC Therapeutics. If you look at Slide 3, we recently completed a successful initial public offering, providing the company with the capital to execute on our broad clinical development program and earlier stage pipeline. This includes our CD25 targeting Kami program in solid tumors, the CD22 program in adult ALL and our XL and CAG1 programs.
In particular, we are pleased with the progress of our longer clinical program. In this morning's press release, we highlighted new longer data, which is now available on the virtual EHA Annual Congress website. The presentations include an oral presentation of new data from the pivotal Phase 2 LONCA trial and an e poster of the Phase onetwo combination trial of LonCA plus Ibrutinib. The Phase 2 data presented today shows the monotherapy Lonka demonstrated important anti tumor activity with an overall response rate of 48.3% and a complete response rate of 24.1% and meaningful durability. These data are very encouraging and continue to reinforce the significant single agent anti tumor activity and manageable toxicity profile of VLONCA and its potential to become the foundation for treatment for patients with relapse or refractory diffuse large B cell lymphoma.
Based on these data, we plan to file the long cut monotherapy BLA during the second half of this year. Our CMC plans are on track to meet the BLA timeline and we continue to prepare our organization with the build out of our commercial, market access and medical affairs teams in advance of the anticipated commercial launch next year. The second data presentation is an of interim results of a Phase onetwo trial highlighting the potential to advance Lonca into earlier lines of therapy in combination with other treatments. The data being presented here today show that the combination of Lonka and Ibrutinib in a Phase onetwo clinical trial of relapsedrefractory DLBCL and mental cell patients looks encouraging with an overall response rate of 75% and a complete response rate of 58.3% of the 60 micrograms per kilogram dose used in the expansion cohorts. These data support the growing evidence of the activity of Lonka and leave us even more encouraged by the potential to bring a new treatment option to patients in the relapsed refractory DLBCL setting.
Let me now turn over to our Chief Medical Officer, Jay Feingold to review today's data in more detail. Jay?
Thank you, Chris. Good morning, everyone. Let me start by reviewing the data from our pivotal BODES-two trial. As shown on Slide 5, this trial was a single arm, multicenter, open label Phase 2 study that evaluated the safety, efficacy and pharmacokinetics of Blanca as a monotherapy in patients with relapsed or refractory DLBCL. Patients received 30 minute intravenous infusions of Lonka once every 3 weeks at a dose of 150 micrograms per kilogram for the first two cycles followed by 75 micrograms per kilogram for subsequent cycles up to 1 year or until disease progression, unacceptable toxicity or other discontinuation criteria, whichever occurred first.
A total of 145 patients participated in the study. As you can see on Slide 6, the study included patients with very poor prognosis, such as double hit and triple hit and transformed disease. The study also included patients who never responded to first line therapy and patients who were refractory to all prior lines of therapies, as well as patients who had high grade B cell lymphoma and high risk genetics. Patients in this study had a meeting of 3 prior lines of therapy. Turning to the next slide.
As Chris mentioned earlier, monotherapy Blanca demonstrated important antitumor activity with an overall response rate of 48.3% and complete response rate of 24.1% in the overall study population. Patients refractory to first line or all prior lines of therapy had an overall response rate of 38% 36% respectively. This data reflects the significant activity Lonca can achieve even in these difficult to treat patients. If you turn to Slide 8, we are pleased to see that as data has matured, we have seen an increase in duration of response with a meaningful median duration response of 10.25 months. On Slide 9, you can see that toxicities were manageable and no new safety concerns were identified.
Bone marrow suppression was common but manageable and the rate of febrile neutropenia was only 3.4%. Most common non hematologic grade 3 and higher treatment emergent adverse event was elevation of the liver enzyme GGT seen in 16.6% of patients. It's important to note that this who have failed the meeting of 3 prior lines of therapy represents an opportunity for patients with limited treatment options to benefit from MANCA and in patients with a complete or very deep partial response, the possibility of undergoing a stem cell transplant, which is considered the best option for long term survival. And now turning to the data presented in the e poster on Slide 11. The LOTUS-three trial is evaluating the combination of Lonka and Ibrutinib in a Phase III trial of relapsed refractory DLBCL in mantle cell lymphoma patients.
Lonka is administered as a 30 minute intravenous infusion using a standard 3 plus 3 dose escalation design at doses of 60 or 90 micrograms per kilogram. Patients receive ONCA every 3 weeks for the first two cycles with concurrent fixed dose Ibrutinib 5 60 milligrams per day given orally up to 1 year. On Slide 12, as of the April 6 data cutoff, 25 patients were enrolled, 23 with DLBCL and 2 with MCL. These patients received a median of 2 cycles of MANCA with 19 patients at the 60 microgram per kilogram dose and 6 patients at the 90 microgram per kilogram dose. Slide 13 shows that early clinical data is promising with an overall response rate of 75 percent and a complete response rate of 58.3 percent at the launch of dose of 60 micrograms per kilogram in combination with Ibrutinib in patients with non germinal center DLBCL and mantle cell lymphoma.
The patients with only DLBCL in that cohort had an overall response rate of 73% and a complete response rate of 64%. The protocol has been amended to include GCB DLBCL patients. On the next slide, you will see that 2 dose domain toxicities were observed in a 90 microgram per kilogram cohort. One DLT was possibly related to Ibrutinib and the other was probably related to both drugs. No DLTs have been observed in patients receiving the selected regimen for Phase 2.
The 2 most frequent Grade 3 and higher treatment emergent adverse events have been thrombocytopenia and anemia. We chose the regimen of 60 micrograms per kilogram of WANCA with 5 60 milligrams mibrutinib for cohort expansion the regimen that will be used in the forthcoming Phase 2 portion of the study. Turning to Slide 15. In summary, we are pleased with the early data for Lonka in combination with Ibrutinib. The combination had promising antitumor activity and a manageable toxicity profile.
This study continues to enroll MCL and GCB DLBCL patients in the expansion phase and we anticipate opening the Phase 2 portion of the study soon. In summary, the data presented at EHA for Lonca monotherapy will be the basis for the BLA that we intend to submit in the second half of twenty twenty. The encouraging early data for Lonca in combination with ibrutinib suggested the combination can be safely administered and that there is significant anti lymphoma activity. The benefit risk profile provides a strong basis for continued development of this combination. With that, I will now turn the call back over to Chris for closing remarks.
Thank you, Jade. As you can see, we've made excellent progress with the LOCKA clinical program. We're excited by these data and pleased to be preparing the BLA for submission in the second half of this year. The longer program illustrates the potential of the PVD ADC platform and the remarkable productivity of both the preclinical and clinical R and D teams. We are pleased to be moving forward not only with Lonka, but with our earlier stage pipeline as well.
Before we take your questions, I'd like to thank you for joining the call, especially in these extraordinary times. I trust you and your families are safe and well. We will now open the call for questions. Operator?
Thank Our first question comes from the line of Matthew Harrison at Morgan Stanley. Please go ahead. Your line is open.
Thank you. Good morning, everybody. So I guess 2 from you. So one on Lonka monotherapy. On durability, can you just, I guess, clarify for us how many patients at risk did you have out on the curve?
I didn't see the numbers at the bottom. And I guess what I'm trying to make sure we understand is how robust is the tail of this data set at this point compared to the data set that you had previously presented? And then second on the combo, I guess talk about the dose response and why you picked the lower dose and I think more importantly, what do you need to do to maybe accelerate that into a potential pivotal study for earlier lines? Thanks.
Thank you, Matthew. And I'll ask Jay to address both those questions, please, Jay.
Sure. Good morning. Matthew, in terms of the availability of response,
when we first showed the first data set at ASH, which was 52 patient futility announced data set, the patients furthest out had were about 8 months. Currently on the slide that I'm showing today, the 1st outpatients are about 15 months. Obviously, this data will continue to mature, but this is the data we have as of today. In terms of the dose response in the combination trial, the patients of 90 micrograms per kilogram certainly responded, but the 2 DRPs made that dose unacceptable from a safety profile point of view. Therefore, we chose to expand the cohorts of 60 micrograms per kilogram.
In view of the fact that the first three patients treated 60 micrograms per kilogram all the way into remission, complete remission by 6 weeks. So that is a dose we chose to take forward into expansion cohorts. We've amended the trial so that we can start the Phase 2 portion of the study in the same trial and that will be initiated in the near future.
Thank you very much.
Thank you. And we have one further question in the queue so far. So just a reminder, if you do wish to ask And the next question comes from the line of Boris Peaker at Cowen. Please go ahead. Your line is open.
Great. Good morning. Congratulations on the excellent data. My first question, in the pivotal study, you enrolled fairly sick patients with poor prognosis and baseline characteristics. So you said you had double hit, triple hit, transformed disease, non responders to frontline therapy.
And some of these were excluded by some of your competitors. I'm just curious, how can you capture this kind of distinction for patient enrollment in the product label, so you could market that element of your pivotal study?
Joe, again, I'll ask you to address that please.
Sure. Of course, obviously the eventual labeling will be dependent upon discussion with FDA. We would anticipate that FDA would follow the usual policy and give us the indication for a blood population of DLBCL patients who have failed at least 2 guidelines of therapy. That was the population that was studied in this study. We can't obviously compare ourselves to what label will look like and not only in a position to discuss the differences in the population.
I think they speak for themselves in terms of patients we included and the patients have included in some of the more recent competitive studies.
Okay. My last question on the duration of response, obviously, you showed a significant increase here. Curious if there is a specific patient subgroup that drove the increase relative to the prior update or is it just longer follow-up was the key?
At this time, what I can tell you is that it appears to be longer follow-up. But we're still doing analysis of the data and we don't have all the subset analysis completed yet.
Great. Thank you very much for taking my questions.
Thank you. And we've had one further question joining the queue so far. That's from the line of James Eason, who's a private investor. Please go ahead. Your line is open.
Good morning. Thank you. I was wondering when you apply for the long term BLA, do you apply for the break its breakthrough designation at the same time or is that totally separate? And typically, how long does the FDA take to come back with a yes or no on the breakthrough designations?
Thank you for that question. We haven't disclosed our approach to breakthrough designation. We haven't applied the breakthrough designation yet for the longer program. But as you'd imagine, we've been having regular discussions with the FDA as we develop these agents, and we'll be looking to file for accelerated approval when we file the BLA.
Thank you.
Thank you. Okay. That seems to be the final question coming through. So I'll hand back to our speakers for the closing comments.
Thank you very much, and thank you, everybody, who's joined this call. As I say, we're very pleased with this data. And I think the ibrutinib combination study does show the potential to move longer into earlier lines of therapy and the broad single agent activity, as Boris Peaker pointed out, across patient population that included hard to treat populations, even patients that have never responded to any dry line of therapy. And we saw responses across that population. So we're excited to be moving through all of LOGCA and look forward to announcing the filing of the BLA in due course.
So thank you very much, everyone.