Gone for good.
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Don't forget the pancreatic cancer phase II KM plot
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=88568995
In the context of the second-line phase II KM plot, and the three preclinical KM plots, this tail
seems much more believable.
Sunstar, you show the glioma study, but there was also the prostate study, shown in my post here:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=88599931
and the vaccine created using the immunocytokine 2aG4-IL2 for breast cancer. Here is the KM plot from this paper:
Enhancing the potency of a whole-cell breast cancer vaccine in mice with an antibody-IL-2 immunocytokine that targets exposed phosphatidylserine
Huang X, Ye D, Thorpe PE.
http://www.ncbi.nlm.nih.gov/pubmed/21557977
Here is the half-life plot from the betabodies poster presented at AACR 2013.
Note this is for mouse versions (2aG4) of bavi and a mouse betabody.
In the phase I paper already referenced we have this for bavituximab
Here is the pdf from the Journal for ImmunoTherapy of Cancer.
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-1-5.pdf
GlaxoSmithKline's research chief in China fired for data fraud
June 11, 2013 | By John Carroll
The head of GlaxoSmithKline's R&D operation in China has been fired while another researcher has resigned following a company probe into allegations that company investigators had "misrepresented" data on interleukin-7 research published in Nature Medicine.
News of the allegation of misconduct and the internal probe it inspired has been bubbling around the industry over the past few days, with reports in Pharmalot and other industry pubs. Nature reported that GlaxoSmithKline spokesperson Melinda Stubbee confirmed that Jingwu Zhang at the GlaxoSmithKline Research and Development Center's department of neuroimmunology in Shanghai "originally claimed to have found data suggesting that the signaling molecule interleukin-7 caused a subset of T cells known as T helper 17 (TH17) cells taken from people with multiple sclerosis to multiply. The finding complemented other research in the field suggesting that genetic differences in the cell receptor for interleukin-7 might put some individuals at risk for developing multiple sclerosis--an autoimmune disease thought to involve helper T cells."
Zhang was fired, another unidentified employee resigned and three others were suspended from their jobs pending a final review by the company.
"Regretfully, our investigation has established that certain data in the paper were indeed misrepresented," GlaxoSmithKline said in a statement. "We've shared our conclusion that the paper should be retracted and are in the process of asking all of the authors to sign a statement to that effect, according to Nature Medicine's procedure."
Getting a reputation for employing researchers who play fast and loose with data can have damaging repercussions, especially for a major pharma company like GSK. Incidents like these can undermine the integrity of all its research in China, a growing hub for drug development work. And Derek Lowe, an investigator and prominent industry blogger at In The Pipeline, notes that it's the kind of scandal that raises plenty of additional questions that need to be answered.
"How, for one thing, did this happen in the first place?" asks Lowe. "On whose initiative were results faked? Who was supposed to check up on these results, and was there anything that could have been done to catch this problem earlier? Even more worrying--and you can bet that plenty of people inside GSK are thinking this, too--how many more things have been faked as well? You'd hope that this was an isolated incident, but if someone is willing to whip up a batch of lies like this, they might well be willing to do much more besides."
Nothing new here. The abstract for the Soares et al Nature Medicine paper is here:
http://www.nature.com/nm/journal/v14/n12/abs/nm.1885.html
I posted this image of a poster from the 2011 CBDST meeting a while back.
There was also this poster from the 2010 CBDST meeting.
Thurly, I saw that the squamous patients in the first NSCLC trial had the lowest response rate.
However, that was based on 8 patients so I don't think you can make too much from that number.
Also, we don't know the survival numbers for those 8, it could be that their survival rate
did not reflect their response rate. In that same poster the info is given about the safety
and what prompted the suspension of enrollment for squamous patients. That event may
have been particular to that one patient because of the location of the tumor. Based on the MOA
for bavi I don't see why squamous patients would not benefit just as well as non-squamous patients.
Something for the future.
The ASCO 2010 poster is here:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=51223631
Fire Fox,
I believe the reason the squamous patients were excluded in both the Avastin and Bavi first-line trials
was due to a concern for adverse events. In the Bavi case I don't think there is any reason to think
it would not work as well in the squamous cell type. If I remember correctly, this was a question put
to Steve King at the annual shareholders meeting and he said that it would be something worth doing.
You have to give me more to go on than that, or just look through my posts.
http://investorshub.advfn.com/boards/profile.aspx?user=93643
The big news from ASCO is not about any individual drug, or company, it is the change in attitude about cancer immunotherapy.
Now that big pharma has endorsed cancer immunotherapy in a big way with their anti-CTLA-4 (Yervoy [BMS]), and anti-PD-1 (nivolumab [BMS], lambrolizumab [Merck]), and anti-PD-L1 (BMS and Roche) drugs the news is getting out. Check out this article in today's NY Times, which mentions my hero Dr. William B. Coley,
http://www.nytimes.com/2013/06/04/health/promising-new-cancer-drugs-empower-the-bodys-own-defense-system.html?ref=health&_r=0
Asian patients, as in Japanese and Chinese, do live longer. But, these were from India, AND you can see on the
subgroup analysis table that the Asian subgroup had a higher HR number (closer to 1) than the European and
United States patients. If the Asian patients were a factor then their HR number would be smaller, not larger.
In other words, bavi + docetaxel was of more benefit to the US and European patients than to the Asian patients,
contrary to your claim.
Sorry, I posted this by mistake on the Biotech Values board in response to
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=88598114
I won't do that again!
Asian patients, as in Japanese and Chinese, do live longer. But, these were from India, AND you can see on the
subgroup analysis table that the Asian subgroup had a higher HR number (closer to 1) than the European and
United States patients. If the Asian patients were a factor then their HR number would be smaller, not larger.
In other words, bavi + docetaxel was of more benefit to the US and European patients than to the Asian patients,
contrary to your claim.
It is approved for two of the big four cancers.
http://www.gene.com/patients/medicines/avastin
Avastin is approved, in combination with intravenous 5-fluorouracil-based chemotherapy, for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum; in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen; in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC); and for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.
Avastin did extend PFS, but not OS, in newly diagnosed glioblastoma. This is the same situation as in metastatic breast cancer.
The PFS result is not a predictor of OS result.
Chicago -- June 1, 2013 -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced final results from the Phase III AVAglio study in people with newly diagnosed glioblastoma, the most common and aggressive form of primary brain cancer. Final results confirmed people who received Avastin® (bevacizumab) plus radiotherapy and temozolomide chemotherapy benefited from a significant improvement in progression-free survival (PFS) compared to those who received placebo plus radiotherapy and temozolomide chemotherapy. Overall survival (OS) was not significantly improved in the study.
As previously announced, Avastin plus radiotherapy and temozolomide chemotherapy significantly reduced the risk of the glioblastoma worsening or death by 36 percent compared to radiotherapy and temozolomide chemotherapy plus placebo (PFS as assessed by trial investigators, a co-primary endpoint: HR=0.64; p<0.0001, median PFS 10.6 months vs. 6.2 months, respectively). People who received Avastin plus radiotherapy and temozolomide chemotherapy did not have a statistically significant improvement in OS (the other co-primary endpoint), compared to those who received radiotherapy and temozolomide chemotherapy plus placebo (HR=0.88; [95% CI 0.76, 1.02], p=0.0987). Median survival was similar in both arms (16.8 months vs. 16.7 months, respectively). No new safety findings were observed in the AVAglio study and adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications.
http://www.gene.com/media/press-releases/14447/2013-06-01/genentech-announces-final-phase-iii-stud
Interview with Dr Wolchok about PD-1/PD-L1 from the ASCO meeting.
http://chicago2013.asco.org/dr-jedd-d-wolchok-immunotherapy-drugs-and-cancer-treatment
Sorry, this is a reply to
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=88410900
As exwannabe noted, the patients had not progressed after their initial radiochemotherapy treatment.
This is totally different than the bavi second-line trial, or any second-line trial, that enrolls
patients who have progressed after their initial treatment. The patients enrolled also had
locally advanced stage III disease, and not metastatic disease. The subgroup is interesting in
that it was prespecified, and the MOS was statistically significant (p=0.0160). The number of
patients in that subgroup was quite large (n=806).
http://www.4-traders.com/ONCOTHYREON-INC-1411129/news/Oncothyreon-Inc-Oncothyreon-Announces-Data-for-L-BLP25-and-PX-866-to-be-Presented-at-American-Soci-16866805/
The ASCO abstract, which stated that a patient discontinued with Bavi, but still remains in the trial
receiving paclitaxel, was written months ago. I do not believe they would "replace" her, it is all part of
the trial to see what safety issues arise, including "infusion related reactions". So when it was announced
on April 29th that the trial had completed enrollment with 14 patients I believe that patient was probably
still enrolled in the trial and receiving paclitaxel.
You can't really compare this with anything else. The number of patients involved is way too small.
Also, as the abstract shows the prior treatments received by the enrolled patients varies quite a bit.
That makes any possible comparison difficult. If this was a first-line trial it would be easier.
The point of this phase I trial is to see if the combination of paclitxel and bavi has activity in
HER2-negative MBC, and is safe. Both of which seem to be true so far.
No, no one was dropped. Read what I wrote.
The phase 1 HER2-negative breast cancer trial.
At last year's AACR annual meeting a poster was presented on this trial.
http://www.peregrineinc.com/images/stories/pdfs/aacr_2012_mbc_ist.pdf
At the time the "best response" results were given as:
CR 2
PR 1
SD 0
PD 2
not yet assessed 1
of the 5 patients assessed the ORR was 3/5, or 60%. Note the objective response rate = complete response (CR)
+ partial response (PR), it does not include stable disease (SD). Also note that this was the "best response"
observed at the time of assessment, and is not the best overall response determined when the trial has been completed.
Because of that, the "best repsonse" can change from the first assessment to later assessments.
This is shown in this table from the RECIST guidelines (v1.1)
Now the abstract from this year's ASCO annual meeting lists these as the "best response to date"
CR 1
PR 6
SD 1
PD 2
not yet assessed 4
so, all 14 patients have been enrolled, and 10 have been assessed at least once. This gives an ORR of 7/10 = 70%.
Note that one of the CR from the first assessment has become something else, but we can't be sure what (PR,SD, or PD).
This means that the cancer came back at the later assessment time.
It is interesting that 7/14 patients have triple-negative metastatic breast cancer. This is a
particularly hard type of MBC to treat so it will be of interest to see the final results for them.
While Peregrine needs money....
Strapped Texas cancer centre built pricey office suite for president’s wife
24 May 2013 | 16:27 BST | Posted by Meredith Wadman | Category: Biology & Biotechnology, Health and medicine, Industry, Lab life, Science communication
The financially stressed MD Anderson Cancer Center in Houston, Texas, seems to have invested at least US$1.5 million in capital funds in a new ‘corporate’ office suite that will be home to Lynda Chin, the wife of MD Anderson president Ronald DePinho. The revelations come in an article published today in The Cancer Letter.
CANCER LETTER
The Letter used the Texas Public Information Act to obtain 680 pages of documents that describe the project as “Dr. Chin Office Renovation”. However, the article argues:
A renovation it was not. The 25,000-square-foot suite, much of it south-facing, is new, located on the sixth floor of the just-constructed South Campus Research Building III.
Chin, who moved to MD Anderson when DePinho became the cancer centre’s president in 2011, is the scientific director of the fledgling Institute for Applied Cancer Science (IACS), a drug-discovery centre, and chair of the cancer centre’s department of genomic medicine. The office was built to house the genomic medicine department and the IACS, which aims to enlist drug companies in promising collaborations. For instance, the IACS in December announced a partnership with drug-maker GlaxoSmithKline, with the goal of producing cancer-fighting antibodies.
Among the itemized expenses reported in The Cancer Letter article are nearly $28,000 for settees, lounge chairs and occasional tables for the IACS, and about $210,000 for translucent walls in the 2,323-square-metre space. The spending on the walls required a variance, or special permission, from the University of Texas system’s executive vice-chancellor for health affairs, Kenneth Shine. (An architect’s rendering of some of the translucent panels is pictured above.)
In a statement to Nature, MD Anderson defended its actions, noting that IACS has raised $15 million in donations:
The renovations of space for the Institute for Applied Cancer Science and Department of Genomic Medicine — both new entities for MD Anderson — transformed a traditional academic office suite to a work environment and meeting area for a science/business enterprise, a concept new not only to MD Anderson, but most of academic medicine….The existing space was not configured to support this new concept.
The “redesigned” space, it added, would “create an open environment of communication, provide an appropriate meeting space with high-level industry decision makers and support a new suite in computational biology”.
This is not the first time that Chin has landed in the public spotlight since she arrived at the huge, high-profile centre. Last year, there was an outcry after an IACS team headed by Chin was awarded an $18-million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) that bypassed scientific peer review.
The 17 May issue of The Cancer Letter (available only to subscribers) reported that DePinho announced austerity measures — such as suspension of merit raises and slowing of hiring — in an e-mail to MD Anderson employees on 15 May. It read, in part:
For most of Fiscal Year 2013 (FY13), our operating expense has exceeded our operating revenue — meaning that we’ve spent more than we’ve made from providing our patient care services. What we’re facing today is much like what you’d face with your own checkbook if you spent more than you were paid each month for several months.
Updated with new comments from MD Anderson.
Cj,It is very encouraging for me to see that all the Thorpe lab personnel have been combined with the Brekken lab.
Hopefully this bodes well for the continuation of Thorpe's research.
When Prolonged PFS Is Not Enough
From Cancer Discovery, May 23, 2013
Progression-free survival (PFS) is well-established as a potential endpoint in clinical trials, but judging its predictive ability for cancer drug approvals can raise some tricky questions.
Such questions, along with concerns about the design of a pivotal phase III trial, were center stage in April when the U.S. Food and Drug Administration's (FDA) Oncologic Drug Advisory Committee (ODAC) recommended against approving the VEGF inhibitor tivozanib (Aveo Oncology) for the treatment of renal cell carcinoma (RCC).
The trial of tivozanib, performed primarily with patients in Eastern Europe, revealed that the drug provided a statistically significant improvement in PFS. Patients who received tivozanib had an average PFS of 11.9 months, compared with 9.1 months among control patients treated with sorafenib (Nexavar; Onyx Pharmaceuticals), which, along with sunitinib (Sutent; Pfizer), is 1 of 2 standard therapies for RCC.
However, overall survival (OS) showed the opposite trend: patients in the control arm lived an average of 29.3 months, compared with 28.8 months among patients in the tivozanib arm.
Based on those results, and on questions about how well treatment protocols for the patients mirrored standard practice in the United States, ODAC recommended rejecting the drug by a vote of 13-1. The FDA itself is generally expected to follow suit, especially since agency officials provided a harsh analysis of the trial data at the hearing.
The worrisome OS data simplified ODAC's decision, but the application raised familiar questions about when PFS findings should justify drug approvals, as they did for sunitinib and a number of other drugs approved in recent years.
Regulators “have good reason to be skeptical about PFS,” says Mario Eisenberger, MD, a professor of oncology and urology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, MD. “There's precedence now showing that drug approvals based on PFS have had to be recalled later,” he says, such as the withdrawal of bevacizumab (Avastin; Genentech) in metastatic breast cancer.
Among the potential limitations of PFS data, its measurements not only are of shorter duration than OS, but also may vary depending on the specific schedule of tumor assessments, notes a May 2013 review in Clinical Cancer Research. Issues also can crop up in how the tumor images are acquired and how tumor progression is assessed, particularly since assessment may be done locally or by a central review group. Additionally, data censoring (for example, removing data for patients who drop out of a study) can be more prevalent on one arm of the trial than the other, potentially distorting PFS results.
Such factors can obscure the connection between treatment-related PFS improvements and extended lives, says Susan Bates, MD, a senior investigator at the National Cancer Institute's Center for Cancer Research. For that reason, regulators are looking for a substantial difference in PFS—for instance, a doubling of the measure compared to controls—that might better predict a clear OS advantage, she says.
Regulators also look for trial protocols that match those in the United States, emphasizes Mikkael Sekeres, MD, ODAC committee chair and a staff physician at Ohio's Cleveland Clinic Taussig Cancer Institute.
During the tivozanib trial, patients on the control arm could cross over to the experimental arm as second-line therapy, but not vice-versa. “Crossover should have been allowed on both arms,” as is standard practice in the United States, says Sekeres. “In our view, the treatment rationale was disingenuous. There is nothing wrong with conducting clinical trials in Eastern Europe, or elsewhere, as long as the sponsor ensures the conduct of the study is the same as it would be here.”
©2013 American Association for Cancer Research.
Yes, it does. We don't know if including them in the phase 2a trial had any effect on the MOS.
Neither the bavi phase 2a first-line NSCLC, or the other trial I used for control comparison (TLF),
excluded patients with squamous cell cancer. The bavi trial had 8/49 (16%) patients with
squamous cell NSCLC, as seen in the patient demographics in my post. The other trial did not
list the cell types. The Avastin first-line NSCLC trial excluded patients with squamous cell cancer
I wrote an e-mail previously in which I had presented a much better comparison trial for
the old phase 2a first-line NSCLC trial instead of using the Avastin + CP first-line trial,
as done by Peregrine in their PR. This shows that an increase in MOS of 40-50% is reasonable
for the current phase 2b first-line NSCLC, assuming the control and treatment arms are balanced.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=83747030
Entdoc, hopefully the presented posters will tell us more about subgroups etc.
Here they are. Not much we didn't already know.
4054 General Poster Session (Board #17H), Sun, 8:00 AM-11:45 AM
Randomized, open-label, phase II trial of gemcitabine with or without bavituximab
in patients with nonresectable stage IV pancreatic adenocarcinoma.
Shuchi Sumant Pandya, Lucas Wong, Andrea J. Bullock, Stephen A. Grabelsky, Merrill Kingman Shum,
Joseph Shan, Kerstin B. Menander, Tony R. Reid; Beth Israel Deaconess Medical Center/Harvard Medical
School, Boston, MA; Scott & White Cancer Research Institute, Temple, TX; Beth Israel Deaconess Medical
Center, Boston, MA; Center for Hem Onc, Boca Raton, FL; Oncology Institute of Hope and Innovation,
Whittier, CA; Peregrine Pharmaceuticals, Inc., Tustin, CA; UC San Diego Moores Cancer Center, La Jolla,
CA
Background: Despite advances in the treatment of metastatic pancreatic cancer (PC), there is critical need
to develop novel therapies.Median survival with combination chemotherapy is limited to less than one year
and only the optimally conditioned patients can tolerate these therapies. Bavituximab (B) is a monoclonal
antibody (mAB) directed againstphosphatidylserine (PS) that causes vascular shutdown and reactivation of
the innate and adaptive immunity in animal models. Preclinical data in mouse PC models indicate that
gemcitabine (G) increases PS exposure and the addition of a mAb targeting PS reduces tumor burden, visible
liver metastases, microvessel density, and increases tumor macrophage infiltration compared to G alone
(Beck et al. 2006). The purpose of this trial is to evaluate and compare the efficacy and safety of the
combination of G+B vs. G alone as first line therapy in pts. with nonresectable Stage IV PC. Methods:
Seventy patients were randomized (1:1) to receive G 1000 mg/m2 on days 1, 8, and 15 every 28Edays with
or without weekly B 3mg/kg IV until disease progression or unacceptable toxicities. Key eligibility criteria
were Stage IV PC, ECOG <=2, measurable disease, age >=18 years, total bilirubin <=1.5xULN, and adequate
renal, hematologic, and hepatic function. The primary efficacy endpoint was overall survival (OS) and
secondary endpoints included overall response rate (ORR) and progression free survival (PFS). Results: Of
the 70 (G/G+B 34/36) patients randomized, 67 (G/G+B 33/34) received study treatment and 63 (G/G+B
31/32) were evaluable. No significant difference was seen in age, gender, race or ECOG. At analysis 87%
deaths had been reported in G and 72% in G+B group. Median OS estimate is 5.2 months for G and 5.6
months for G+B. No difference between groups was observed in PFS (median 3.9 months for G and 3.7
months for G+B). ORR was 13% for G and 28% for G+B. Most AEs were grade 1-2 and typical of
exposure to G. Conclusions: In this patient population with extensive disease burdens and limited treatment
options, G+B was well tolerated and demonstrated moderate activity in tumor response and survival.
Clinical trial information: NCT01272791.
567 General Poster Session (Board #4F), Sat, 1:15 PM-5:00 PM
Phase I clinical trial of bavituximab (Bavi) and paclitaxel (P) in patients (pts) with
HER2-negative metastatic breast cancer (MBC).
Pavani Chalasani, Marilyn Marron, Kathryn Clarke, Kathy Schmidt, Alisa Powell, Maria Iannone,
Alison Stopeck; University of Arizona Cancer Center, Tucson, AZ
Background: Bavituximab is a novel tumor vascular targeting agent. It is an unconjugated, chimeric
immunoglobulin G1 monoclonal antibody directed against phosphatidylserine (PS). PS is externally
expressed on endothelial cells when exposed to hypoxia and/or other physiological stressors frequently
observed in tumor-associated vasculature. On attaching to PS, Bavi triggers antitumor effects by inducing
antibody-dependent cellular cytotoxicity and promoting antitumor immunity. Methods: We conducted a
phase I clinical trial of Bavi in combination with P in pts with HER-2 negative MBC. Pts were treated with
weekly P (80mg/m2 for 3/ 4 weeks) and weekly Bavi (3mg/kg for 4/ 4 wks). Microparticle generation,
activation and circulating endothelial cell apoptotic markers were measured by flow cytometry. Results: 14
pts with MBC were enrolled. Median age at MBC diagnosis was 50yrs. Seven pts had triple negative MBC;
4 pts presented with de-novo metastatic disease. Prior treatments included chemotherapy in the adjuvant/
neoadjuvant setting (8); metastatic setting (2); adjuvant hormonal therapy (3). Best responses to date include
complete response (1), partial response (6), stable disease (1), progressive disease (2) and too early to
evaluate (4). Bavi related toxicities include grade2/3 infusion related reactions in 2 pts (1 discontinued
Bavi). Bone pain, fatigue, headache and neutropenia were the most common adverse effects. 1 pt had a
catheter associated upper extremity thrombosis requiring anticoagulation. Laboratory correlative studies
revealed no evidence of platelet activation of PAC-1 or P-Selectin. Median platelet and endothelial
microparticles decreased from baseline in response to therapy. Conclusions: Bavi is a novel vascular
targeting agent that is well tolerated in combination with P. Early results show promise in terms of clinical
responses with 8 of 10 evaluable patients having clinical benefit. Early biomarker results suggest no effect
of therapy on platelet activation but decreases in circulating microparticles is observed. Clinical trial
information: NCT01288261.
8095 General Poster Session (Board #39C), Sat, 8:00 AM-11:45 AM
Randomized, blinded, placebo-controlled phase II trial of docetaxel and bavituximab
as second-line therapy in locally advanced or metastatic non-squamous non-small
cell lung cancer.
Mikhail Shtivelband, David R. Spigel, David E. Gerber, Minish Mahendra Jain, Olga V. Ponomarova,
Davit Giorgadze, Joseph Shan, Kerstin B. Menander, Chandra Prakash Belani; Ironwood Cancer and
Research Centers, Chandler, AZ; Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN;
UT Southwestern Medical Center, Dallas, TX; Ruby Hall Clinic, Pune, India; R.E. Kavetsky Institute of
Experimental Pathology, Oncology and Radiobiology, Kiev, Ukraine; Chemotherapy and Immunotherapy
Clinic, Tbilisi, Georgia; Peregrine Pharmaceuticals, Inc., Tustin, CA; Penn State Hershey Cancer Institute,
Hershey, PA
Background: Bavituximab (B) is a monoclonal antibody against phosphatidylserine (PS) with a selective
tumor vascular-directed immune response. The purpose of this trial is to evaluate the efficacy and safety of
B or placebo (P) combined with docetaxel (D) in patients with locally advanced or metastatic non-squamous
NSCLC. Methods: Patients were randomized 1:1:1 to receive 75 mg/m2 of D every 21 days for up to 6
cycles combined with weekly blinded infusions of P, 1mg/kg B or 3 mg/kg B until disease progression or
unacceptable toxicity. Primary efficacy endpoint was overall response rate (ORR). Secondary endpoints
included progression free survival (PFS) and overall survival (OS). Safety was evaluated by adverse events
(AEs), vital signs, CBC, biochemistry, urinalysis, coagulation, ECG. Post study unblinding, a PK substudy
revealed vial coding discrepancies in the P and 1 mg/kg vials. As a result, data from these two groups were
pooled to form the control (C) arm in the analysis. Results: Forty-one patients were entered into the 3mg/kg
B+D arm and 80 into the control arm. No significant differences were seen in age, gender, ethnicity or
disease stage. ECOG 2 was 13% in C and 24% in 3 mg/kg B+D arms. At this analysis, 54% death events
have been reported in 3 mg/kg B+D and 71% in C arm. ORR is 17.1%/13.8% and median PFS is 4.5/3.3
months for 3 mg/kg B+D/C. Median OS is 11.7 months for 3 mg/kg B+D and 7.3 months for C. The safety
profile for 3 mg/kg B+D was similar to that of C in severity and frequency. No other safety signal was
identified. Conclusions: This randomized, placebo-controlled phase 2 trial demonstrated a positive trend
favoring 3 mg/kg B+D in ORR, PFS and OS. 3 mg/kg B in combination with D was well tolerated and is
the planned dose for Phase 3. Clinical trial information: NCT01138163
I would be surprised to get all that today. These are abstracts, nothing more, and were written months ago.
The posters will have more, and more up-to-date, info on them. Jay should post the posters to Peregrine's
website after they are presented at the meeting on June 1st and 2nd.