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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.

Earnings Call Part 2:

• Q&A with Eli Lilly and Company CEO