Good afternoon, welcome to the Iovance Biotherapeutics clinical development program update conference call. All participants are in a listen-only mode. Following the formal remarks, we will open up the call for your questions. Please be advised that this call is being recorded at the company's request. Now, I would like to turn the conference over to Tim Morris, Chief Financial Officer at Iovance. Sir, please go ahead.
Thank you, operator. Good morning, everyone, thank you for joining us today. With me on the call is Maria Fardis, President and CEO. I'd like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, clinical trial plans and results, potential future applications of our technology, manufacturing capabilities, regulatory feedback and guidance, licensing and collaboration agreements, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. Now I'll turn the call over to Maria.
Thank you, Tim. Good morning, everyone. Yesterday, we issued a press release that you can find on our website at iovance.com, which includes highlights of the updated interim data from our ongoing studies in advanced cervical cancer and advanced melanoma from the ASCO abstract released last night, dosing of the first checkpoint-naïve patient, this combination of TIL plus KEYTRUDA, and an update on our research efforts to increase the potency of our TIL product. On today's call, we'd like to review these results and address questions about what the data mean for Iovance as we move towards submission in 2020 and in filing for regulatory approval of lifileucel in advanced clinical program. We are pleased to report that in the ongoing innovaTIL-04 study of patients with advanced cervical cancer, treatment with LN-145 resulted in an objective response rate of 44% per RECIST 1.1.
These results include one complete response, nine partial responses, and two unconfirmed partial responses due to not having reached a follow-on assessment, and a disease control rate of 89%, with 11 of the 12 patients maintaining responses at three and a half months of median follow-up. The mean patient age was 47 years, and study participants had a mean of 2.6 prior lines of therapy. As a reminder, last October, we reported an objective response rate of 27% in 15 patients who had a median of five prior therapies. The data cut off for the abstract was early February of 2019. Improved responses were observed in four patients with longer follow-up. Mean TIL cells infused was 28 billion, and median IL-2 doses administered was six. The adverse event profile was generally consistent with underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens.
The ASCO poster presentation will include additional graphics, including a swimmer lane and a waterfall, patient characteristics, and a table of adverse events. We plan to present longer follow-up of the 27 patients at the meeting. These updated data from 27 evaluable patients are highly encouraging. The range in ORR for second-line therapies is between 4% for chemotherapy and 14% for pembrolizumab. A review of therapies in development for cervical cancer, along with feedback from our early market research with KOLs, suggests this objective response rate in this study could become a treatment option that provides clinically meaningful improvement in available care for these patients. In February, we received Fast Track designation for LN-145 for advanced cervical cancer. We have been in active dialogue with the FDA and plan to meet with them to discuss this data and the path to registration for LN-145 in advanced cervical cancer.
I now turn to melanoma data. Our observation from cohort 2 of the innovaTIL-01 study in advanced melanoma continue to be compelling. In these patients, lifileucel continued to demonstrate a 38% objective response rate in 55 patients following failure of prior therapies, including PD-1 checkpoint inhibitors. The 38% response is the same rate that we reported last year in 47 patients at SITC, and we are encouraged that our observations are consistent with additional patient enrollment. The 38% overall response rate includes 1 additional CR for a total of 2 complete responses, 18 partial responses, and 1 unconfirmed partial response due to not having reached a follow-on assessment. In this study, patients were heavily pretreated with a mean of 3.1 prior therapies, including anti-PD-1, and had high baseline tumor burden. Overall disease control was 76%.
At 7.4 months median follow-up, responses were maintained in the majority of the patients, with only four of 21 responders having had progressed at the time of data analysis, which was late January 2019. Mean number of cells infused was 28 billion, and a median of IL-2 doses administered was six. Adverse events resolved to baseline two weeks post-TIL infusion, a potentially important benefit of a one-time TIL therapy. The ASCO poster presentation will include graphics such as swimmer lane and waterfall, patient characteristics, and a table of adverse events. The ASCO data presentation will include additional patients, which is over 60 patients in cohort 2. The data from cervical and melanoma studies will be presented at the ASCO annual meeting, and abstracts are now available at the ASCO website. We would like to emphasize that this data are from ongoing studies and will continue to mature.
We continue to enroll the pivotal cohort 4 of our melanoma study. In addition, we expect to engage the FDA in discussing a path for registration of LN-145 for advanced cervical cancer. Our basket study allows for enrollment of PD-1 or PD-L1 naive patients to receive TIL plus KEYTRUDA. We are pleased that the first checkpoint-naive melanoma patient has been dosed in phase II IOV-COM-202 study. While our other studies focus primarily on patients that have experienced prior immunotherapies, PD-1 or PD-L1 naive patients represent an important population where TIL therapy could provide clinically meaningful benefits. The potential for TIL therapy in this population further emphasizes Iovance's commitment to offering a one-time treatment regimen with the potential for a deep, durable response to PD-1 or PD-L1 naive patient population. This is a landmark for Iovance, and we look forward to enrolling additional checkpoint-naive patients into this study.
On our research front, we will present our first set of data from our peripheral blood lymphocyte product, called IOV-2001, at the 24th Congress of excuse me, European Hematology Association, held in June 2019 in Amsterdam. A brief overview of the manufacturing duration as well as potency and phenotype of the IOV-2001 product will be shared at that meeting. In addition to support efforts to improve the potency of TIL, Iovance has entered into a collaboration with Genocea to evaluate its ATLAS platform. As reported by the company at the American Association for Cancer Research, AACR, 2019 annual meeting, melanoma patients receiving lifileucel have a unique mutational landscape, suggesting that high mutational load solid tumors such as melanoma may benefit from treatment with a patient-specific polyclonal product such as Iovance's TIL product. The company will utilize the ATLAS platform to see if better TIL can be identified.
I'll now turn the call over to the operator for your questions. Operator?
Thank you. Ladies and gentlemen, if you have a question at this time, please press star then number 1 on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question comes from the line of Biren Amin of Jefferies. Your line is open.
Hi, guys. Thanks for taking my questions. Congrats on the data yesterday in abstracts. Just to start with the melanoma study, Maria, will we get duration or response from the melanoma trial at ASCO?
Yes. Hi, Biren. Thank you for the question. Yes. We felt that the data was immature as we had presented preliminary data at SITC, and we wanted to make sure that we have more mature data to provide at ASCO. Yes, DOR will be provided at ASCO.
On the LN-145 cervical study, how many of the Gen 2 patients were PD-1 naive versus PD-1 failures? If you had PD-1 failures in the Gen 2 cervical, did you see any responses? I think you've seen PD-1 refractory patients in melanoma respond. Thanks.
Yes. We did not break it down on the abstract, but we will provide that as part of ASCO present in the slides and the poster. We do have patients that are post PD-1, so PD-1 failures. We will provide information regarding their responses as part of the poster. A second point since you questioned about the DOR, I also want to highlight that the DOR data that we would have available for cervical will also be provided at ASCO as well.
Got it. Maybe just one last question. In cervical, how many of the patients at baseline were PD-L1 negative? It seems KEYTRUDA is not approved for this population in cervical.
Excellent point. We will try and provide that information as well. PD-L1 sort of a characterization at baseline is not common for cervical patients. Not many investigators do that, although the product itself is indicated only for PD-L1 high expressors. To the degree we have that data, we'll provide it. Yes, you're correct.
Great. Thank you.
Sure.
Thank you. Our next question comes from the line of Mark Breidenbach of Oppenheimer. Your line is open.
Hey. Good morning, guys, and thanks for taking the questions, and congrats on the very nice data updates. I guess related to one of the previous questions, it's obviously a pretty big increase in ORR in cervical from what you've previously reported. Just how are you viewing this in terms of, are you attributing the improvement more to the fact that you're using a Gen 2 product in this cut, or are you attributing at least some of that to the changes you've made in the eligibility criteria in the cervical trial?
Thank you for that question, Mark. I think both are playing a role here. We are aware, there's a reason we made the changes, exactly as you noted. We believe that Gen 2 may be, in fact, a better product. That by itself may have had an impact. We also limited the number of priors in our cervical study from one prior systemic, which led to the patients that we initially enrolled having had five median prior therapies, to amending the protocol to one to three priors. Even with that, we still have well over two prior lines of therapy for all the patients. The median was at 2.6, so they're still heavily pre-treated. Nonetheless, I think that limiting the number of priors as well as limiting the amount of exposure to anti-PD-1 are all contributing factors to a better response rate.
As one would expect, we have seen a similar pattern in melanoma, we are not surprised seeing a better response rate in cervical now.
Okay, got it. Can you tell us the data cutoffs for the cohort 2 update in melanoma between what we'll actually see at ASCO versus what was included in the abstract?
Sure. The abstract data cutoff was late January 2019. We are going to cut the data for melanoma for the poster in May, you will have additional data follow-up, longer follow-up. At the same time, the cohort enrolled more than 60 patients into the cohort. It over-enrolled. We will provide all the patient data that we have in-hand. All of that will be visible to the community.
Okay, fantastic. Thanks for taking the questions, and congrats again.
Thank you, Mark.
Thank you. Our next question comes from the line of Joe Catanzaro of Piper Jaffray. Your line is open.
Hey, guys. Thanks for taking the question, and let me add my congrats on the data here. The first question from me, I was wondering if maybe you could help us understand whether the additional CR we're seeing in melanoma and maybe the new CR in cervical, are those new patients that we're seeing, or are those prior patients who converted from PR to CR with a longer follow-up?
We do see both, Joe. Thank you for your question. We certainly see deepening of response, as I noted, in cervical as we have a longer follow-up. Both phenomena is seen. There is new patients that may have a CR, but most patients start with a PR, and they get a deeper response over time.
Okay, got it. I just wondered about the unconfirmed responses in both melanoma and cervical. Is that because there simply hasn't been enough follow-up, or are some of those patients fallen off the study? Just wanted to know if there is chance for those unconfirmed responses to be confirmed with longer follow-up.
Yes, definitely. All the unconfirmed PRs are due to lack of second follow-up. You will see the results of that as part of the ASCO poster themselves. We generally never report if a patient only has one PR, and subsequent to that, the PR does not confirm. That's not something we report. We report based on RECIST 1.1. If you see an unconfirmed PR, it's only because the second assessment has not been reached.
Okay, got it. Thanks for taking the questions and looking forward to the full data at ASCO.
Thank you, Joe.
Thank you. Our next question is on the line of Madhu Kumar of R.W. Baird. Your line is open.
Hey, guys. Thanks for taking our questions, and I apologize for the background noise. First, just to make sure I get this right, the four patients who progressed in the melanoma trial
Hey, Madhu, you're cutting off. You want to repeat your question?
Sorry. In the melanoma cohort, there were four patients who progressed after response.
Madhu, we are not able to hear you at all, I'm sorry, we're not able to hear your question. Do you want to come back into the queue from a different line?
Sure. Yeah.
Okay, our next question is from the line of Yuliya Livshits of Truist. Your line is open.
Thanks. Congrats again, guys, on the data, thanks for taking my question. On the cervical program, you have the planned meetings with FDA to discuss regulatory path, as you mentioned. Can you give us a bit more color on the status of those meetings and whether the regulators have already seen these most recent data before now? Thanks.
I think I heard your question, whether we have initiated the regulatory interactions and whether FDA has seen this data. Is that what you asked?
Yeah, thanks. I have a follow-up.
Sure. I can confirm that yes, the regulators have seen this data.
Great. Just in terms of safety, the melanoma abstract mentions adverse events, I imagine likely associated with IL-2 dosing resolve to baseline two weeks post-TIL infusion. The cervical abstract doesn't specifically state this. Is there anything you can share with us now on whether the TEAEs that you've seen in the cervical program follow a similar pattern in terms of kinetics to what you've seen in melanoma? Thanks.
I think I understood your question. I believe what you're asking is whether the kinetics of TEAEs, treatment emergent adverse events, in cervical and melanoma are the same. Is that your question?
Yeah, exactly.
Sure.
In terms of kinetics.
Yeah, they are. In fact, what we see is treatment emergent adverse event profile, in general, is very consistent between various indications, which is a confirmation that bulk of these TEAEs are associated with chemotherapy and IL-2. Yes, from a timing perspective and timing to resolution, they're also very consistent.
Thanks. That's it for me.
Thank you.
Thank you. As we have no more questions at this time, we would now like to turn the call back over to Maria for closing remarks.
Thank you, operator. We are glad to be able to report these encouraging results, and we are working as efficiently as possible to make TIL therapy an accessible treatment for patients who need better therapeutic options. Thank you for joining us on the call today. Have a good day.
Ladies and gentlemen, thank you for your participation in today's conference. This concludes today's program. We hope you all have a pleasant day. You may now disconnect.