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
AI
