”Patients Also Had Increase in Progression Free, Overall Survival Rates” Adding the monoclonal antibody bavituximab to docetaxel chemotherapy doubles overall response rate and improves progression-free survival and overall survival in late-stage non-squamous, non-small cell lung cancer (NS-NSCLC) patients who have already received one prior chemotherapy regimen, according to research presented at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology. This symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago.
Docetaxel is the standard second-line treatment for stage IIIB and stage IV NS-NSCLC patients. Researchers in this phase II, nine center, double-blind, randomized study evaluated the efficacy and safety of docetaxel plus a placebo (control arm) versus docetaxel plus either 1 mg or 3 mg bavituximab. The 117 evaluable patients were randomized to receive one of the three regimens every 21 days for up to six cycles. Patients received the same regimen for each cycle.
The overall response rate for the 1 mg bavituximab arm was 15% and 17.9% in the 3 mg arm, approximately double the control arm rate of 7.9%. Median progression-free survival was 4.2 and 4.5 months for the bavituximab arms, respectively, compared to three months for the control arm.
The trial was unblinded after 18 months, at which point the median overall survival had been reached in the control arm at 5.4 months (61% of patients died); however, neither bavituximab arms had reached median overall survival (fewer than 35% of patients died).
“This rigorous phase II trial demonstrates that not only is bavituximab well tolerated when given with docetaxel but it improves response rates, progression free survival and overall survival of second-line chemotherapy in patients with advanced NSCLC,” said David Gerber, MD, lead author of the study and an assistant professor of internal medicine at University of Texas Southwestern Medical Center in Dallas who specializes in lung cancer treatment. “If a phase III trial confirms these findings, bavituximab could become a major component of standard treatment for patients with this challenging disease.”
The abstract, “Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Bavituximab Plus Docetaxel in Patients with Previously Treated Locally Advanced or Metastatic Non-Squamous Non-small Cell Lung Cancer (Top-line Results),” will be presented during the Plenary Session at 12:30 p.m., Central time on September 7, 2012. To speak with David Gerber, MD, please contact Michelle Kirkwood or Nicole Napoli on September 6-8, 2012, in the press office at the Chicago Marriott Downtown Magnificent Mile at 312-595-3188.
Abstract LBPL2 Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Bavituximab Plus Docetaxel in Patients with Previously Treated Locally Advanced or Metastatic Non-Squamous Non-Small-Cell Lung Cancer (Top-line Results) David E. Gerber 1, M. Joppert2, D. R. Spigel3, D. P. Singh4, D. Giorgadze5, M. Shtivelband6, O. V. Ponomarova7, J. Shan8, C. P. Belani9, 1Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, 2Florida Cancer Specialists, Ft. Myers, Fla., 3Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, 4Department of Radiotherapy and Clinical Oncology, S.M.S. Medical College and Attached Hospitals, Jaipur, India, 5Chemotherapy and Immunotherapy Clinic, Tbilisi, Ga., 6Ironwood Cancer and Research Centers, Chandler, Ariz., 7RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Kiev, Ukraine, 8Peregrine Pharmaceuticals Inc., Tustin, Calif., 9Penn State Hershey Cancer Institute, Hershey, Penn. Bavituximab (B), a monoclonal antibody directed against phosphatidylserine, (PS) has been shown to localize selectively to tumor vasculature, synergize with chemotherapy, cause vascular shutdown in tumors and reactivate innate and adaptive tumor immunity.
Purpose/Objective(s): To evaluate the efficacy and safety of two separate doses of bavituximab (1 and 3 mg/kg) combined with docetaxel (D) vs. D plus placebo (P) as second line therapy in patients with locally advanced or metastatic non-squamous NSCLC.
Materials/Methods: This phase II, multicenter, double-blind study, randomized patients (1:1:1) to receive 75 mg/m2 of D every 21 days up to 6 cycles and weekly blinded infusion of P, 1 mg/kg or 3 mg/kg of B until disease progression or toxicity. Key eligibility criteria were Stage IIIB and IV, non-squamous NSCLC previously treated with first line systemic chemotherapy, ECOG status <=2, measurable disease by RECIST and adequate hematologic, hepatic and renal function. The primary efficacy endpoint was overall response rate (ORR) by RECIST 1.1 and secondary endpoints were progression free survival (PFS), duration of response (DR) and overall survival (OS). Safety was evaluated by adverse events, vital signs, laboratory measurements (CBC, biochemistry, urinalysis and coagulation), ECG and human anti-chimeric antibody (HACA) formation.
Results: Of the 121 patients randomized, no significant differences were seen in baseline characteristics (gender, age, ethnicity, ECOG or disease stage.) Based on 117 evaluable patients, the ORR was 7.9% for the D + P, 15.0% for the D + 1 mg/kg B and 17.9 % for the D + 3 mg/kg B cohorts, respectively. Median PFS was 3.0, 4.2 and 4.5 months, respectively. At the time the Independent Data Monitoring Committee (IDMC) recommended to unblind the trial, median OS had been reached at 5.4 months in the control group (61% death events), while <35% of death events had been observed in the bavituximab-containing groups. B + D was well-tolerated and no safety concerns were identified by the IDMC.
Conclusions: In this double-blind, randomized, placebo-controlled, multicenter Phase II study in patients with Stage IIIB and IV non-squamous NSCLC, bavituximab in combination with docetaxel was well-tolerated and all endpoints (response, PFS and OS) demonstrated trends toward superiority for both experimental arms. Importantly, though median OS has not yet been reached in either bavituximab-containing cohort, there is a clear and persistent separation of the survival curves warranting further development of bavituximab.
Author Disclosure Block:David E. Gerber: E. Research Grant; Peregrine Pharmaceuticals, Inc. M. Joppert: None. D.R. Spigel: None. D.P. Singh: None. D. Giorgadze: None. M. Shtivelband: None. O.V. Ponomarova: None. J. Shan: K. Stock; Peregrine Pharmaceuticals, Inc. Q. Leadership; Peregrine Pharmaceuticals, Inc. C.P. Belani: None.
= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =BACKGROUND: 9-4-12: “Ground-breaking Research to be Presented at Lung Cancer Symposium” • Two webcast news briefings will preview top studies… https://www.astro.org/News-and-Media/News-Releases/2012/Ground-breaking-research-to-be-presented-at-lung-cancer-symposium.aspx The 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology, sponsored by ASCO, ASTRO, IASLC and The Univ. of Chicago, will host 2 news briefings on top lung cancer research from its meeting Sept6-8, 2012, in Chicago.
Friday, Sept. 7, at 7:15amCT/8:15amET Study findings previewed: • Crizotinib [Pfizer’s Xalkori] reduces tumor size in patients with ALK positive lung cancer • Brain radiation after lung cancer treatment reduces risk of cancer spreading • Standard chemo treatment provides higher survival rate than experimental regiment in late-stage lung cancer patients • Adding bavituximab to 2nd-line chemotherapy doubles response rate in late-stage lung cancer patients Register here (look for confirm. email): https://astro.webex.com/astro/j.phpED=141711842&RG=1&UID=1143492497&RT=MiM3
= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = CHICAGO SUMMARY: ( http://tinyurl.com/cvr7fp4 ) Chicago Symposium in Thoracic Oncology, Sept6-7 => 3 Bavi presentations & posters on Peregrine’s NSCLC trials (highlighted by Dr. Gerber’s Sept7 Plenary Talk on the ongoing randomized Bavi+Doce 2nd-Line NSCLC Trial), and another interesting general talk by Dr. Gerber on Tumor-Diameters vs. OS in NSCLC. • Sept7 1:40-1:50pm Dr. David Gerber (UTSW), Late-breaker PLENARY talk on Bavi+Doce 2nd-Line NSCLC Trial • Sept6 5:00-6:30pm Dr. K.H. Dragnev (PI, Dartmouth-Hitchcock MC), POSTER on Bavi+PC 1st-Line NSCLC Trial • Sept6 8:00-12:00pm Dr. J.Grilley-Olson (UNC), “PUB. ONLY” on Ist#3, Bavi+Pemcarbo/1st-Line NSCLC Trial - - - - - - - - -Non-Bavi Specific: • Sept6 6:10-6:25pm Dr. David Gerber, Poster Discussion on Tumor-Diameters vs. OS in NSCLC
"With this (2nd-Line NSCLC) data in hand, we now have a number of events to look forward to… We have 2 Late-Breaking presentations coming up… Our goal in the Sept. 7th Chicago data presentation ( http://tinyurl.com/9vt2vbo ) is to be able to talk a little bit more about the (2nd-Line NSCLC) MOS and where we're at evaluating that in both Bavi arms. Even though we haven't reached MOS, and certainly may not have reached it by then, we still will be able to talk a little bit more about where we're at in that process. we'll also be able to talk more about how the statistics in the trial are trending, and how we put those kinds of events together into our thinking about a Phase III trial design. Our goal is to get the data out there, but we're already beginning our EOP2 meeting preparations. We're working actively on a Ph.3 trial design; our goal is to have the EOP2 meeting before the end of the year, which will put us on track for initiating a Ph.3 trial by the middle of 2013. . ."we have a number of key value-drivers coming up. The 2nd-Line NSCLC study is obviously continuing to be the focus, as we have what we believe to be a clear pathway to move that program forward. MOS data, again this is a time-to event and we haven't reached it yet, but at some point in all likelihood we will. We have the upcoming oral presentation at the ASCO Chicago Symposium (9-7-12), as well as at ESMO (9-29-12/Vienna), which gives us a great opportunity to talk about the clinical data and to describe to people why we're so excited about the potential of this trial, and why, not just ourselves, but key opinion leaders that are active in the pgm, as well as potential partners, believe this is a clear path into Phase III and to move the pgm forward.. . The data cut at the end of April already showed that we had clearly reached MOS in the ctl-arm. As we sit here now today, several months later, we still haven't reached that min. # of events for either of the Bavi arms to be there (MOS). It's not quite as simple as a 1-to-1, ie, 1 month doesn't mean it's 1 month addl. in OS, but what we can say is, it [2nd-Line NSCLC MOS] is going to be a very positive result, it's just a matter now of magnitude. Importantly, because we often get this question, potential partners do not need to reach MOS to make a decision on partnering. We do not need to reach MOS in the Bavi arms at this point to plan what the pivotal trial will potentially look like. At this point, we have data, and I think we'll be able to make it clearer when we present the full package on Sept. 7th in Chicago. Basically, the longer, the better, obviously - it's not just great for the program, it's great for the patients, because, again, we do have patients that are out and still even on treatments as we speak."
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