Eli Lilly's (LLY) Management Hosts Analyst Meeting to Review the Data Presented at ASCO 2014 Conference Call (Transcript)

Jun. 3.14 | About: Eli Lilly (LLY)

Eli Lilly and Company (NYSE:LLY)

Analyst Meeting to Review the Data Presented at ASCO 2014 Conference Call

June 3, 2014 15:00 ET

Executives

Sue Mahony - President, Lilly Oncology

Dr. Richard Gaynor - Senior Vice President, Product Development and Medical Affairs

Brian Stuglik - Vice President, Global Marketing

Ben Anderson - Global Product Leader, Ramucirumab

Andrew Oxtoby - Global Product Leader, Necitumumab

Colleen Mockbee - Global Product Leader, Abemaciclib

Phil Johnson - Investor Relations

Ilissa Rassner - Investor Relations

Analysts

Tim Anderson - Sanford Bernstein

Steve Scala - Cowen

Salim Syed - ISI Group

Operator

Ladies and gentlemen, thank you for standing by. Welcome to the Lilly Oncology Pipeline Update Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time. (Operator Instructions) As a reminder, this conference is being recorded.

I would now like to turn the conference over to our host Dr. Sue Mahony, President of Lilly Oncology. Please go ahead.

Sue Mahony - President, Lilly Oncology

Thank you, Jeff. Thank you to everyone for joining us today to review key data for multiple disclosures that were held at this year’s Annual Meeting of the American Society of Clinical Oncology.

Joining me on today’s call are Dr. Richard Gaynor, Senior Vice President, Product Development and Medical Affairs; Brian Stuglik, Vice President of Global Marketing and our global product team leaders of ramucirumab, necitumumab, and abemaciclib, Ben Anderson, Andrew Oxtoby, and Colleen Mockbee as well as Phil Johnson and Ilissa Rassner from the Investor Relations team and a few other oncology team members.

Before we begin, let me remind you that we anticipate making projections on forward-looking statements based on our current expectations. Our actual results could differ materially due to a number of factors, including those listed on Slide 2. For additional information about the factors that affect our business, please refer to our Forms 10-K and 10-Q filed with the Securities and Exchange Commission. The information we share about our pipeline and products is for the benefit of the investment community. It is not intended to be promotional and is not sufficient for prescribing decisions.

With Alimta, we have held a leadership position in lung cancer for the past decade helping many patients with this disease, which is the leading cause of cancer-related mortality in the world. The recent launch of Cyramza in advanced gastric and gastroesophageal cancer means Lilly can now also play an important role in helping patients with gastric cancer, the third leading cause of cancer death. With Cyramza’s approval as a single agent in advanced gastric cancer, three positive Phase 3 trials in the last year and the potential for two more Phase 2 readout in the next six months we are very confident about the near-term opportunities that we have to expand our oncology franchise.

Today, we will focus on data from three studies, the REVEL Phase 3 trial that studied ramucirumab in combination with docetaxel versus docetaxel alone in second line non-small cell lung cancer patients. These data were part of the ASCO press conference Saturday and were published in The Lancet and presented at ASCO yesterday. The SQUIRE Phase 3 study that evaluated necitumumab in combination with gemcitabine and cisplatin versus Gem-Cis in frontline squamous non-small cell lung cancer. This study was also presented yesterday at ASCO. And the Phase 1 breast and lung cohort expansion results for abemaciclib, our CDK-4/6 inhibitor. The single agent breast data were presented early this year at AACR for the lung cancer and combination breast cancer data were presented here at ASCO.

So, let’s start with ramucirumab and it is my pleasure to turn the call over to Ben Anderson, the Global Product Leader for ramucirumab.

Ben Anderson - Global Product Leader, Ramucirumab

Thank you, Sue. We are excited about the REVEL data, which showed an overall survival benefit with ramucirumab as the second line treatment for patients with non-squamous or squamous non-cell lung cancer. If approved in this setting, ramucirumab positions us to leverage our current infrastructure and grow our leadership in lung cancer. Despite advancements in genomics and identification of predicted biomarkers such as EGFR mutations and ALK rearrangement, there is still no oncogenic targeted therapy for the majority of non-small cell lung cancer patients.

For these patients, chemotherapy remains the treatment of choice. For patients that are eligible for second line treatment do not have an EGFR mutation or an ALK translocation, which is the majority of the patients, only three agents, docetaxel, pemetrexed and erlotinib are approved by the FDA. Furthermore, outside of subgroup analyses, no other trials other than REVEL evaluating the addition of a new agent to standard second line chemotherapy have demonstrated improved overall survival in lung cancer patients, so clearly new options are needed to improve the outcomes for non-small cell lung cancer patients who progress after first line therapy. REVEL is the first positive Phase 3 study of a biologic in combination with chemotherapy to demonstrate improved survival compared to chemotherapy alone in second line non-small cell lung cancer in the overall study population.

Many of you are likely familiar with the study design, so let me quickly highlight just a few elements of the trial. REVEL is a global randomized double blind placebo control Phase 3 study of ramucirumab in combination with docetaxel versus docetaxel alone in patients with stage 4 non-small cell lung cancer whose disease progressed during or after first line platinum based chemotherapy. Patients with both squamous and non-squamous tumor histology were allowed to participate in study. Randomization was stratified by performance status, gender, prior maintenance therapy and geographic region. The primary end point was overall survival and secondary end points included progression free survival, objective response rate and safety. Base line patient characteristics and stratification factors were well balanced between the arms. Approximately 25% of patients had squamous tumor histology, 24% of patients received prior taxane therapy and 14% of patients received prior bevacizumab.

As shown on Slide 8, ramucirumab in combination with docetaxel demonstrated a statistically significant improvement in patients’ overall survival with a 14% reduction in the risk of death and a median overall survival of 10.5 months versus 9.1 months for the docetaxel arm. The Kaplan-Meier survival curves demonstrated early and consistent separation throughout the study observation period with the ramucirumab arm demonstrating a 43% one year survival rate and a 21% two year survival rate. We are very pleased that ramucirumab was able to prolong survival in a study where docetaxel performed in line with prior clinical studies.

Slide 9 shows a forest plot analysis of the overall survival across subgroups, the effect of ramucirumab on overall survival was consistent favoring the ramucirumab-docetaxel arm across the majority of prognostic subgroups including squamous and non-squamous histologies. In addition, all secondary efficacy end points favored the ramucirumab investigational arm. Investigator assessed PFS was significantly longer in the ramucirumab-docetaxel arm with a hazard ratio of 0.76 or 24% reduction in the risk of progression or death. Meeting our progression free survival was 4.5 months for the ramucirumab-docetaxel arm versus three months for the docetaxel arm. And the Kaplan-Meier curves again separated early and remained separated for the duration of the observation.

The objective response rate and the disease control rate were also highly statistically improved for the ramucirumab-docetaxel arm as compared to the placebo docetaxel arm. We are very encouraged that the REVEL data showed a consistent benefit for ramucirumab across all of these efficacy measures, objective response, disease control rate, progression free survival and overall survival.

Now let me transition from efficacy data to the safety profile. Most of the clinically significant toxicities were chemotherapy driven and manageable with dose adjustments and appropriate supported care. The most common grade 3 or higher adverse event with an incidence of 5% or higher under ramucirumab plus docetaxel arm compared to the control arm included decreases in white blood cell count, febrile neutropenia, fatigue and hypertension. No grade 5 toxicity was observed for these events which includes no deaths due to febrile neutropenia. Given ramucirumab’s antiangiogenic properties there are a few pathway related AEs that I would like to discuss while patients on the ramucirumab arm experienced higher incidence of Grade 1, 2 bleeding events including epistaxis, the difference in the rates of gastrointestinal and respiratory tract bleeding events, including hemoptysis and pulmonary hemorrhage were low between the arms and were consistent in the squamous and non-squamous subgroups. Hypertension occurred more frequently in the ramucirumab docetaxel arm with approximately 5% reporting Grade 3 hypertension which in most cases, was adequately managed using standard anti-hypertensive treatment.

In conclusion, we are very pleased to have the first agent in combination with chemotherapy to demonstrate improved overall survival compared to chemotherapy alone in second line non-small-cell lung cancer for squamous and non-squamous histologies. And we look forward to submitting this indication to the FDA later this year.

The REVEL study is the third positive Phase 3 trial for ramucirumab and this data reinforces our confidence in the overall ramucirumab program. We are looking forward to the read out of two additional Phase 3 trials this year. We anticipate disclosing top line data for REACH, the second line hepatocellular trial mid this year and for RAISE, the second line colorectal cancer trial by the end of the year. We are pleased to announce that we have submitted the supplemental BLA to the FDA based on the RAINBOW results and look forward to updating you on the progress of the Cyramza launch in the near future.

Now, I will turn the call over to Andrew Oxtoby, Global Product Leader for necitumumab.

Andrew Oxtoby - Global Product Leader, Necitumumab

Thanks, Ben. As Sue mentioned, ramucirumab is just one step towards increasing our leadership in lung cancer. We believe that necitumumab, a human IgG-1 anti-EGFR monoclonal antibody represents an important milestone for patients with first line squamous non-small cell lung cancer and if approved can further enhance our leadership in lung cancer.

Squamous NSCLC is a hard to treat disease with a high unmet medical need. In contrast with the progress seen in non-squamous NSCLC, limited treatment advances have been observed over the past two decades in squamous NSCLC. Developing new treatments is especially challenging in squamous NSCLC with our no proven oncogenic drivers to involve treatment decisions. So, we are very encouraged of the Phase 3 SQUIRE study, not only increased overall survival, but also showed consistency across two secondary endpoints as the first line treatments in patients with Stage 4 metastatic squamous non-small-cell lung cancer.

With a 1,093 patients enrolled, SQUIRE is the largest Phase 3 study ever conducted in advanced squamous NSCLC. While the trial design is pretty straightforward, there are few elements of the trial I would like to highlight. Necitumumab was combined with Gem-Cis, one of the preferred treatment options in squamous NSCLC and uses a flat dosing schedule with administration on Day 1 and Day 8 in a three-week cycle.

The inclusion criteria are broader than what is typically seen in lung cancer trials, as patients with ECOG performance status of 0, 1 and 2 were committed in the trial. Therefore, the trial population in SQUIRE is similar to the patients that physicians see in their daily practice. Upon completion of the chemotherapy-based treatments, patients on the investigational arm who exhibited a complete response, partial response or stable disease continued on necitumumab’s single agent treatments until the disease progressed.

Overall, survival is the primary endpoints of the study and secondary endpoints included progression-free survival, overall response rates, and safety. The baseline demographics and disease characteristics were well-balanced between both arms and were representative of a typical patient population with advance squamous NSCLC as the majority of patients were males with the history of smoking.

We are very encouraged that SQUIRE met its primary endpoints by showing a statistically significant improvement in overall survival with a hazard ratio of 0.84 and a P value of 0.012. The median overall survival is 11.5 months in the investigation of necitumumab arm and 9.9 months in the Gem-Cis comparator arm. As depicted by the Kaplan-Meier curve, the survival benefits started early in the treatments and showed separation throughout the duration of treatments.

Slide 22 shows the forest plot analysis of the overall survival across subgroups consistency in the overall survival across subgroups including patients with an ECOG performance status of 2 was also very encouraging. In addition to the consistent overall survival benefits seen across subgroups a consistent effect in favor of a necitumumab based regimen was seen across secondary end points. This is evidenced by the statistically significant improvements in progression free survival and disease control rates.

We are not only pleased with necitumumab’s efficacy profile in SQUIRE, but also with its safety profile. The most common grade 3 or higher adverse events occurring more frequently on the necitumumab arm were rash and hypomagnesemia which are known side effects of this class of agents and are generally manageable. There were no increases in grade 3 or higher hematological toxicities, febrile neutropenia or fatigue when adding necitumumab in the chemo doublets. We also see a low incidence of hypersensitivity infusion related reactions in the necitumumab arm.

A higher incidence of venous thrombotic events or VTEs and arterial thromboembolic events or ATEs were seen in the investigational arm compared to the control arm. Grade 3 or higher VTEs and ATEs were observed in less than or equal to 5% of patients in the necitumumab arm versus less than 3% in the control arm. It’s important to note that the VTEs and ATEs with fatal outcomes were uncommon, less than 0.6% of patients and that there was no imbalance in the rate of fatal events between study arms. Overall, we are pleased with the safety profile of necitumumab in combination with chemotherapy.

In conclusion we are encouraged by the efficacy and safety data from SQUIRE. The study met its primary end points showing significant improvements in overall survival with consistent efficacy results for secondary end points and across subgroups. Based on the SQUIRE data necitumumab has the potential to provide a meaningful advance in the first line treatments of metastatic squamous NSCLC patients, patients that have been waiting for the last two decades for the improvements in overall survival. We are pleased to announce that the FDA has granted us fast track status and we continue to expect to submit the BLA before the end of this year.

I will now turn the call over to Colleen Mockbee, the Global Product Leader for abemaciclib.

Colleen Mockbee - Global Product Leader, Abemaciclib

Thanks Andrew. There has been a lot of recent investor attention on CDK 4/6 inhibitor, so I appreciate the opportunity today to highlight the Phase 1 breast and lung cancer results to-date for Lilly’s CDK 4/6 inhibitor abemaciclib. Abemaciclib is structurally distinct from other compounds of its class and was perfectly designed to be a potent and selective inhibitor of CDK 4 and 6 that could be dosed continuously since we believe this to be the optimal schedule given it’s mechanism of actions. Anti-tumor activity was seen across multiple preclinical tumor models of human cancers including non-small cell lung cancer and breast cancer. Based upon the preclinical findings we initiated a Phase 1 dose escalation study evaluating once and twice daily dosing of abemaciclib.

Down here on Slide 29, is the design of the Phase 1 study. I will focus on data from the breast and lung cancer cohorts that were initiated based upon the anti-tumor activity seen in part A. So, preclinical and early clinical activity in advanced lung cancer patients which included some tumor reductions led us to evaluate the safety and efficacy of abemaciclib in advanced lung cancer patients.

Part B, part B study single agent abemaciclib and previously treated metastatic breast cancer patients. This data was initially presented at AACR, April and updated in the poster presented at ASCO a few days ago along with data from part G which evaluated the safety profile of abemaciclib in combination with fulvestrant and drug cancer patients whose disease progressed on a multiple prior therapies.

Let me start with a brief update and with data from the breast cancer cohort and then I will transition to the lung cancer cohort results. Slide (30) shows the eligibility for the two breast cancer expansion cohorts. In both cohorts patients were eligible if they seek the benefits from available therapies. And with single agent cohort patients were enrolled without regard to hormonal status and were required to have measurable disease to assess activity. In the cohort that explored the combination of abemaciclib plus fulvestrant patients were required to have prior hormonal treatment and prior treatment with fulvestrant was allowed. Measurable disease was not a requirement for eligibility. Patients enrolled in the single-agent cohorts had a median of seven prior treatments, all have metastatic disease and greater than 50% of patients have vitro disease that is presence of metastasis in the liver, lung or brain.

This waterfall chart depicts the change in tumor size for patients that received single-agent abemaciclib. This data was outdated from the presentation at AACR. We are now seeing 13 of the 36 hormone receptor-positive patients have greater than 30% reduction in tumor size, 9 of the 13 are constant responses. The overall clinical benefit rate, which includes patients that had a response or a stable disease lasting greater than six months with 49% in the overall population and 61% in patients with hormone receptor-positive disease.

Looking at the left breast cancer cohort, will be evaluated the safety profile of the combination of the bemaciclib with fulvestrant and metastatic breast cancer patients the hormone receptor-positive disease. All patients have received prior therapy with the median of four prior treatments with 17% previously progressing on fulvestrant. The majority of patients have received than two or more metastatic sites with virtual disease present in 50% of patients.

Shown on slide 33, of the most common toxicities of thus have possibly related to treatments. The most common toxicity were neutropenia, and gastrointestinal related events including diarrhea, fatigue and nausea. The neutropenia was uncomplicated and no patients have received neutropenia. No Grade 4 toxicities were reported and there were no discontinuations due to adverse events in this cohort of patients.

It is important to note that the efficacy data for this breast cancer cohort is not matured. At the time of this analysis, 72% of events, 72% of patients remain on treatment. Early evidence of activity is present in three patients with greater than 30% reduction in tumor size of the 10 patients with measurable disease. Of the 18 patients enrolled, 8 patients did not have measureable disease. Thus far, the disease control rate is 72%. We are very encouraged with the safety profile, so that combination with fulvestrant continue to support twice-daily continuous dosing. The data for the combination of abemaciclib as to the growing body of evidence including robust single-agent activity and supports advancing abemaciclib in to larger confirmatory studies in patients with hormone receptor-positive metastatic breast cancer.

Now, I will transition to the result from the lung cancer cohort that were presented for the first time here at ASCO a few hours ago. Patients with non-small cell lung cancer were eligible for this cohort that they seize to receive clinical benefit from available standard therapy at ECOG performance status of 0 to 2 and had measurable disease. While pre-clinical data shows greater sensitivity to KRAS mutant non-small cell lung cancer, we enrolled patients with and without the KRAS patient to ensure to be at a robust data set for determining next steps.

57 patients with non-small cell lung cancer including 29 patients with KRAS mutant disease were enrolled. The primary objective was to evaluate the safety of the single-agent abemaciclib and second theory objective were to document anti-tumor activity and to assess pharmacodynamics and predictive biomarkers. The majority of patients at ECOG performance status of 0 or 1 and all patients had metastatic disease with the majority having disease in two or more sites. It is important to keep in mind that patients have received a median of four prior lines of treatment.

Let me first review the safety data. The most common adverse events were gastrointestinal related including diarrhea, nausea and vomiting, plus also fatigue. The majority of these were Grade 1 or 2. There were no Grade 4 or 5 toxicities reported in the non-small cell lung cancer cohort and one patient discontinued due to nausea. The most common Grade 3 toxicities adverse were leukopenia at 14% and 9% neutropenia.

Slide 37 is a waterfall slide showing present change in tumor size under Y-axis. Each bar represents single patient’s tumor response to abemaciclib. The dark blue bar show the 29 patients that had KRAS mutant non-small cell lung cancer and light blue bars shows those with KRAS wild-type. The three grey bars represent patients whose mutation status was unknown. Patients with KRAS mutant non-small cell lung cancer had a disease control rate of 55% which is higher than that seen in the KRAS wild-type patients. This is consistent with the pre-clinical data showing greater sensitivity of abemaciclib and KRAS mutant non-small cell lung cancer models that I referenced earlier.

Please keep in mind that this is a heavily pretreated population with the median of four prior therapies and the bulk of this line of therapy for non-small cell lung cancer are typically very low. We were encouraged to see robust events of tumor reduction in several patients across the waterfall chart including receptor responses in two patients. Volume of KRAS mutant non-small cell lung cancer and gone with squamous non-small cell lung cancer who also had a CDKN2 evolution.

We are very pleased with the safety and efficacy data that we have generated the dates for abemaciclib and advanced breast cancer and lung cancer patients. We have initiated the late-stage development program in hormone receptor-positive, metastatic breast cancer patients that evaluates abemaciclib both at the single-agent and in combination. The plan includes a confirmatory Phase 2 study of abemaciclib and single-agent in patients that need chemotherapy and two Phase 3 trials, one with abemaciclib in combination with fulvestrant and one with abemaciclib in combination with aromatase inhibitor. And we intent to start a Phase 3 trial in advanced lung cancer patients later this year. This trial of study single-agent abemaciclib HER2 erlotinib and KRAS mutant non-small cell lung cancer patients to progress after two prior chemotherapy regimens a patient population with primarily treated full and treated options were limited.

Now, let me turn the call back over to Sue for a few closing remarks before opening the call for Q&A.

Sue Mahony - President, Lilly Oncology

Thank you, Colleen. So, let me conclude by saying that we’re confident and excited about the future of Lilly Oncology. Well, we’ll continue to leverage our leadership in lung cancer to maximize the value of Alimta and to potentially go into new non-small cell lung cancer indications ramucirumab and necitumumab. Over the past 12 months, we’ve had three positive Phase 3 trials from our ImClone pipeline, thus validating the importance of this acquisition.

We have a robust early to mid-stage oncology pipeline, which we will continue to prioritize, and we will rapidly progress those assets that we believe have the most potential. The early feedback from the U.S. launch of Cyramza as single-agent and advanced gastric cancer is positive and we are focused on ensuring that this launch is successful and we’re preparing for new potential launches. With the potential from several upcoming launches on a pipeline of extremely interesting cancer treatments, we have an opportunity to firmly establish Lilly as one of the leading company in oncology. We are ready to take advantage of this opportunity.

Now, I’d like to turn the call over to Q&A. So, operator, third caller please.

Question-and-Answer Session

Operator

(Operator Instructions) Our first question comes from the line of Tim Anderson with Sanford Bernstein. Please go ahead.

Tim Anderson - Sanford Bernstein

Hi, thank you. I have a few questions. Just a high level one, any substantial risk to the provability, in your opinion, of necitumumab or ramucirumab and their respective indications, given a smaller absolute benefits seen in the hazard ratios in the mid-80%s? How comfortable are you that the regulatory path forward should be fairly clear and unobtrusive with both products? Second question is on ramucirumab, I think the bar to the beat in second-line lung is Tarceva, where the OS benefit is about two months. So your opinion, what would compel a physician to use ramucirumab versus Tarceva in second-line? And then just a clarification question on slide 29 on your CDK inhibitor, you show other cohorts like GBM and melanoma and colorectal, but I can’t tell if those cohorts are ongoing or not and whether you’ve seen responses in those cohorts or not?

Phil Johnson

Great, Tim. This is Phil. Thank you for the questions. I think we have Dr. Richard Gaynor take your first two questions and then Colleen Mockbee take your question on the abemaciclib Phase 1 additional cohorts study. Richard?

Dr. Richard Gaynor

Well, I would say it’s important Tim to recognize that both NSCLC and CYRAMZA both results which we heard yesterday two positive Phase 3 trials that were statistically significant for improvement in overall survival. The squamous trial, again in squamous cell non-small cell lung cancer, this is the first improvement in therapy so far in last several decades, other than chemotherapy, double chemotherapy. So, I think we are very excited about it. It was robust trial, statistically well powered and clinically meaningful with a good risk benefit ratio.

I think we can say the same about ramucirumab REVEL trial, again second line lung cancer following fluoro with platinum and double it, regardless of histology again, regimens available in chemotherapy, docetaxel is an improved regimen. And again addition to chemotherapy in the second line, there really has not been any improvement there. Here again we have a robust trial, consistent actors all endpoints including overall survival.

Read the safety profile, efficacy profile. And I think given the results from both of those trials, we feel confident that they will be reviewed and we’re hopeful that they would be ultimately approved. Now, you asked about erlotinib, and erlotinib has an approval in second and third line patients regardless of histology, but it’s important to note that the comparator there was placebos as support of case. Remember that all of our trials, there is couple of things, unmet medical need and after comparator. We are taking standard of care and improving it. And so it’s not just basically the placebo controlled trial.

That’s really clear. We are taking things where we want to take the standard of care, we want to make it much better. And the last thing that I will say in lung cancer, 1.6 million people die worldwide. And in the US and in Western Europe about 15% of those patients will have either an EGFR or an ALK mutation. But for the vast majority of patients there has been little improvement, for the vast majority of patients who come into physician offices. And we think yesterday we’re proud and I think it’s something that’s really good for the field to have two positive Phase 3 survival trials for patients with lot of unmet medical need.

Phil Johnson

Thanks Richard. Colleen?

Colleen Mockbee

Yes. On the question, on the additional cohort, we have completed enrollment for those cohorts and we have seen activity in particular in melanoma and we had indications of the global glioblastoma cohort with stable disease. However, we’ll have to do additional work to really identify patients most likely to benefit in those areas.

Phil Johnson

Great, thanks Colleen. Jeff, if we could have the next caller please?

Operator

Yes. Our next question comes from the line of Steve Scala from Cowen. Please go ahead.

Steve Scala - Cowen

Thank you. In a symposia at ASCO on Sunday, a discussion referred to recent failed hepatoma (indiscernible) inhibitor. Now, admittedly, the discussion didn’t mention ramucirumab, but I guess ramucirumab data may have been made public by virtue of the comment at this symposia. So, can you confirm or deny that ramucirumab was unsuccessful in the hepatocellular study? Thanks.

Sue Mahony

Do you want me to take that one?

Phil Johnson

Sure. Go ahead.

Sue Mahony

We can deny. We want to actually show what the data, to be honest with you Steve. But, no, we can deny that there is leak of information about this data and we don’t have the data yet. We should have it reset in the mid this year. We are awaiting that data.

Steve Scala - Cowen

Thank you.

Phil Johnson

Jeff, next caller please.

Operator

Our next question comes from the line of Mark Schoenebaum from ISI Group. Please go ahead.

Salim Syed - ISI Group

Hey, this is Salim in for Mark. Two questions. On the abemaciclib/fulvestrant breast trial, could you just clarify when you saw the six patients who had Grade 3 neutropenia and the four patients who had Grade 3 leukopenia, when did you see that leukopenia and neutropenia occur during treatment? And then a second question, which is related to the first, the safety is cumulative correct, when we are thinking about safety, the longer these trials go on, the safety or the issue only go up. Is that correct? Am I thinking about that correctly? Thank you.

Phil Johnson

Alright, Salim. Thank you very much for your questions. Colleen, do you want to start?

Colleen Mockbee

Yes. So, on the activities that were the neutropenia observed in the fulvestrant combination, that would have been early in the first one to two cycles for the patients. Again the data we reported was very early in treatment.

Salim Syed - ISI Group

And then in terms of whether or not one would expect over time for AUAs increase with longer exposure?

Colleen Mockbee

We have not seen that thus far, the agent cohort for breast cancer is a cohort that we’ve had patients on for a long period of time, as we have not seen an increase appreciably over time. Again, those numbers are small at this time.

Phil Johnson

Okay, great. Thanks Salim. Jeff, next caller, please.

Operator

There are no questions queuing at this time. Oops, we just got one. We have a question from the line of Ramil (indiscernible) from Credit Suisse. Please go ahead.

Unidentified Analyst

Yes, hi. Can you hear me, okay?

Phil Johnson

We can, Ramil. How are you doing?

Unidentified Analyst

Yes, I’m okay. Sorry, for the background noise here. Just a quick question, I think I appreciate the details in your data releases. Just I was aiming oncology was the big theme of this conference, a lot of exciting data in lung cancer and other tumors. So, any updates you can share on your efforts there or sort of the urgency that you sent internally to do any sort of collaborations or acquisitions to get more of a presence in that space? Thanks.

Dr. Richard Gaynor

Yes, thank you for the question. So, the immunooncology field is all exciting data there and something we are very interested in. The way I would really stated in terms of our preclinical efforts, we are putting a lot of efforts in there, in terms of new targets and directing therapies there. And so that’s really very interesting. Another thing that I should say in our current portfolio, we have several molecules where we are actually studying using them and studying their effects on the immune system and that’s a Tgfa program, a small molecule in antibody which inhibits a Tgfa to pathway, Tgfa to be very important in Trex cells, CSF1R antibody and CXCR4 inhibitor.

In additional we really believe that in oncology and I think as you heard at the meeting that combinations are going to become increasingly important. And these will be from different classes, potentially angiogenesis in immunotherapy, targeted agents in immunotherapy and probably a variety of other types of approaches. So we are exploring a variety of opportunities from things in our portfolio that have worked through the immune system and other approaches which may help work with immunotherapy to improve patient outcomes.

Phil Johnson

Okay. Thanks Richard. Jeff, next caller please.

Operator

Our next question comes from the line of Tim Anderson from Sanford Bernstein. Please go ahead.

Tim Anderson - Sanford Bernstein

Thanks for the follow-up. I have not heard any commitment from Lilly on landing additional trials with ramucirumab or necitumumab. So, I am wondering what the development plan is from here? I realize that with ramu, there is ongoing trials, but if you are confident in these programs, then there are earlier lines of therapy that you could pursue in the case of ramu or if there is other tumor types, in the case of neci. So, what is the development plan forward and what are the gating factors?

And then on your CDK-4/6, it looks like it’s really the stable disease aspect of that drug that warrants pushing into registrational trials. There wasn’t much in the way of partial responses. I am wondering if there were any delayed tumor regressions seen with the product or other curious response patterns like you sometimes see with the immunooncology drug?

Phil Johnson

Great, Tim. Thank you for the questions. I think we will have each of the three product team leaders, answer for their respective molecules. Ben, do you want to start us off?

Ben Anderson

Yes. For ramucirumab as you pointed out, we still two ongoing trials. We will have the hepatoceullar cancer mid-year and colorectal cancer towards the end of the year. We are in gastric cancer with two positive Phase 3 trials. And we have a great deal of confidence and potential in gastric cancer. We don’t have any Phase 3 studies to announce today, but we continue to evaluate options in that area. And likewise that effort will – that evaluation will continue as we look at the lung cancer data in more detail.

Phil Johnson

Thank you, Ben. Andrew?

Andrew Oxtoby

With the results of necitumumab, we are pleased with the results in the first indication, which is the first line squamous NSCLC setting. We have a Phase 2 trial, which is ongoing with 162 patients looking at necitumumab with a carbotaxel chemotherapy platform also in squamous patients. And we are evaluating other opportunities both within the lung space and potentially the tumor sites and we will continue those discussions in the coming months.

Phil Johnson

Great. And Colleen?

Colleen Mockbee

Yes. So, on your question around stable disease, actually in terms of abemaciclib, we have robust single agent activity in breast cancer. And again, that was in a heavily pre-treated patient population with a median of 7 prior cycles of therapy. In the hormone-receptor positive, we are seeing in the range of 25% to 30%, which really is robust with a population of that really has limited treatment options. Additionally, in the combination I will remind you that, that is very early data yet we will certainly update that data. Not all patients have measurable disease that we won’t be able to fully report on the response, but we are seeing early indicators of responses in those patients with three having greater than 30% reduction out of 10 patients with measurable disease. So, again in 4 prior lines of therapy, that’s really encouraging and I think surprising.

So, on the lung cancer, you see that we across the waterfall plot had a tumor reduction and on three, they are limited number of actual CRs based on RECIST criteria. However, in this line of therapy, you are going to see some kind of median of four prior treatments that you would not expect really from one single agent RECIST responses here. We also had a lot of patient on treatment for greater than six months, so not only with the activity that we saw in terms of tumor reduction as the patient stay on and having a number of patients (indiscernible) encouraging us to move that into Phase 3, in particular in KRAS mutant population, where really there are no treatment ops.

Phil Johnson

Tim, thanks for the questions. Jeff, next caller please.

Operator

There are no further questions at this time.

Phil Johnson

We can always wait another minute and see if we have got anyone who wants to pullback in?

Operator

(Operator Instructions)

Phil Johnson - Investor Relations

No additional questions, Jeff?

Operator

There are no questions coming up sir.

Phil Johnson - Investor Relations

Okay, thank you very much for joining us this afternoon to discuss the pipeline update for Lilly Oncology. As Sue mentioned in her opening, this is a very exciting time for us. If you think of what’s happened over the last 18 months or so, we had particularly with the InClone pipeline positive Phase 3 data with the REGARD trial presented at ASCO GI in 2013 and second line gastric cancer have led to the recent launch here in the U.S. At ASCO GI in 2014 of this year, we presented the detailed data from the RAINBOW study again second line gastric cancer of ramucirumab this time in combination therapy. I look forward to hearing back from FDA as we have now recently made the submission to them for that potential indication as well. And then it was covered here at ASCO, the main meeting here we have had positive Phase 3 trials for ramucirumab in second line non-small-cell lung cancer, where there are some very few improvements outside of very specialized patient populations and very few compared to an active comparator. So, we are very encouraged with these results and look forward to submission in the second half of this year.

Also very pleased that in the first line squamous non-small-cell lung cancer patient population that we have a positive trial of necitumumab with the SQUIRE study, and again hopeful to have that submission go in before the end of this year. And that as Colleen mentioned both at the AACR meeting earlier this year and at ASCO just today very pleased with the data that we are seeing monotherapy as well as the safety and tolerability in combination therapy for abemaciclib, our CDK-4/6 inhibitor and look forward to the start of that Phase 3 program in both breast cancer and lung cancer this year, so exciting times for Lilly as we look to build on our leadership and oncology. As always, we will keep you posted with our progress. If you have specific follow-up questions, please do feel free to reach out to Ilissa or to me in the coming days and look forward to the continued dialogue. Have a great afternoon and an evening.

Operator

Ladies and gentlemen, that does conclude our conference call. Thanks for your participation and using AT&T Executive Teleconferencing. You may now disconnect.

Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to www.SeekingAlpha.com. All other use is prohibited.

THE INFORMATION CONTAINED HERE IS A TEXTUAL REPRESENTATION OF THE APPLICABLE COMPANY'S CONFERENCE CALL, CONFERENCE PRESENTATION OR OTHER AUDIO PRESENTATION, AND WHILE EFFORTS ARE MADE TO PROVIDE AN ACCURATE TRANSCRIPTION, THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE AUDIO PRESENTATIONS. IN NO WAY DOES SEEKING ALPHA ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY TRANSCRIPT. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S AUDIO PRESENTATION ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS.

If you have any additional questions about our online transcripts, please contact us at: transcripts@seekingalpha.com. Thank you!