Avid Bioservices Inc (CDMO): Comparisons of PPHM’s Completed Ph.2 Bav...

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cjgaddy

Re: cjgaddy post# 68124

Friday, 11/25/2011 4:26:44 PM

Friday, November 25, 2011 4:26:44 PM

Comparisons of PPHM’s Completed Ph.2 Bavi Single-Arm, “Signal-Seeking” Cancer Trial Data [3 Ph2’s: Breast(2) & NSCLC] vs. Avastin & Chemo-Only – updated with MOS data reported June/Aug/Nov 2011.
• If you see any errors, let me know & I’ll correct & re-post.
• All ORR%’s shown on ‘intent-to-treat’ basis, not ‘evaluables-only’.
• Spelling lesson: Avastin=Bevacizumab

= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
I. 2ND-LINE ADV/MET BREAST CANCER (Rep.GA.): BAVI + DOCETAXEL:
http://clinicaltrials.gov/ct2/show/NCT00669591 (15+31=46)
Ph.2 Bavi+Doce n=46: ORR=61%, CR=11% MedPFS=7.4mos, MOS=20.7mos ( http://tinyurl.com/2eoz96r & http://tinyurl.com/3rxqqtk )
. . .Plus, ASCO’10 Bavi poster shows: 19.5%@100%RED, 30.4%@>75%RED, Her2+ 6/7=86% ORR.
Ph.2 Avastin+Doce n=27: ORR=52%, MedPFS=7.5mos, MOS=NotRept. (B. Ramaswamy 2006 http://tinyurl.com/dnfk4y )
HISTORICAL COMP. VS. CHEMO ALONE:
…Ph.3 DOCE/ALONE n=203: ORR=30%, CR=3.4%, MOS=11.4mos (Nabholtz/JCO1999 http://tinyurl.com/3hx3e6o )
- - - - - - - - -
ORR% UPDATE HISTORY FOR PH.2/BAVI+DOCE/BREAST/GA:
6-2-08 PR: “5 of 11 (45%) achieving PR” (1st 11 evaluables, 8wk-scans)
=> 7-2-08 PR: “7 of 15 (47%) achieving PR” (9wks after all S1 enrolled, 8wk-scans)
==> 9-9-08 CC/SK: “9 of 15 (60%) achieving PR” (19wks after all S1 enrolled, ~12/16wk-scans)
===> 10-21-08 PR: “10 of 15 (67%) achieved ORR.” (after 6 of 6 4wk cycles)
====> 10-21-09 PR: “28 of 46 treated (61%) achieved OTR.” (after 6 of 6 4wk cycles)
=====> 6-5-10 ASCO: “ORR=61% (28/46), 11% CR’s (5/46), Med.PFS=7.4mos”
======> 8-24-11 PR: “ORR=61% (28/46), 11% CR’s (5/46), Med.PFS=7.4mos, MOS=20.7mos”
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MBC/RepGA 1st-DOSED: 2-12-08 => 120.0wks a/o 6-1-10
ALL-15-DOSED-Stage1: 4-29-08 => 109.0wks a/o 6-1-10 (1.3/wk)
1st-Screened-Stage2(31): 10-21-08 => 82.0wks a/o 6-1-10
ALL-31-DOSED-Stage2: 5-4-09 => 55.1wks a/o 6-1-10 (1.1/wk)

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II. FRONTLINE ADV/MET BREAST CANCER (India)” BAVI + PACLITAXEL-CARBOPLATIN:
http://clinicaltrials.gov/ct2/show/NCT00669591 (15+31=46) [CP=paclitaxel+carboplatin]
Ph.2 Bavi+PC n=46: ORR=74%, CR=24%, MedPFS=6.9mos, MOS=23.2mos ( http://tinyurl.com/28af5ee & http://tinyurl.com/6wazs9p )
. . .Plus, ASCO’10 Bavi poster shows: 21.7%@100%RED, 39.1%@>75%RED, Her2+ 8/8=100% ORR.
Ph.x Avastin+PC <=I cannot find a MBC trial using Avastin+PC, except this one still recruiting a/o 11-2011: http://clinicaltrials.gov/ct2/show/NCT00654836
HISTORICAL COMP. VS. CHEMO ALONE:
…Ph.2 PC/ALONE n=95: ORR=62%, CR=8%, MedPFS=4.8mos, MOS=16.0mos (Loesch/JCO2002 http://tinyurl.com/6osaeth )
…Ph.2 PC/ALONE n=53: ORR=62%, CR=16%, MOS=NotRept. (Perez/Cancer2000 http://tinyurl.com/7uex7nv )
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ORR% UPDATE HISTORY FOR PH.2/BAVI+PC/BREAST/INDIA:
2-11-09 PR: “7 of 15 (47%) achieving PR” (after 2 of 6 4wk cycles)
=> 4-27-09 PR: “9 of 15 (60%) achieving PR” (after 6 of 6 4wk cycles)
==> 6-5-10 ASCO: “34 of 46 (74%) ORR%, 4/46=9% CR’s” (includes 2 non-evaluables)
===> 11-22-11 PR: “34 of 46 (74%) ORR%, 11/46=24% CR’s, MOS=23.2mos”
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MBC/India 1st-DOSED: 8-11-08 => 94.1wks a/o 6-1-10
ALL-15-DOSED-Stage1: 10-7-08 => 85.0wks a/o 6-1-10 (1.8/wk)
1st-DOSED-Stage2(31): 4-27-09 => 57.1wks a/o 6-1-10
ALL-31-DOSED-Stage2: 9-8-09 => 38.0wks a/o 6-1-10 (1.6/wk)

“Approx. 30% of breast cancers have an amplification of the HER2 gene or overexpression of its protein product. Her2+ breast cancer is associated with increased disease recurrence & worse prognosis.”
NOTE: Her2+ results for both completed Bavi+Chemo single-arm Ph.2 ABC trials: 14/15=93% ORR (n=15)

= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
III. FRONTLINE ADV./MET. NSCLC CANCER (India): BAVI + PACLITAXEL-CARBOPLATIN:
http://clinicaltrials.gov/ct2/show/NCT00687817 (21+28=49)
Ph.2 Bavi+PC n=49: ORR=43%, MedPFS=6.1mos, MOS=12.4mos (http://tinyurl.com/2g5cqof & http://tinyurl.com/3fcz5ok )
. . .Plus, ASCO’10 Bavi poster shows: 4.1%@100%RED, 22.4%@>50%RED.
Ph.3 Avastin+PC n=417: ORR=35%, MedPFS=6.2mos, MOS=12.3mos (Sandler/E4599/2006 http://www.nejm.org/doi/pdf/10.1056/NEJMoa061884 )
HISTORICAL COMP. VS. CHEMO ALONE:
…Ph.3 PC/ALONE n=433: ORR=15%, MedPFS=4.5mos, MOS=10.3mos (Sandler/E4599/2006 http://www.nejm.org/doi/pdf/10.1056/NEJMoa061884 )
…Note: The BAVI+PC results above were achieved using less Chemo (175-v-200 & AUC5-v-AUC6), treating 16% (8/49) more-difficult Squamous in Bavi trial (excluded totally from E4599), and treating higher % of sicker ECOG1 patients than in E4599 (96%-v-60%). See 6-15-11/PR http://tinyurl.com/3fcz5ok , ASCO'10 http://tinyurl.com/2g5cqof , and a discussion of differentiating factors between patient demographics and baselines treated in the 2 trials: http://tinyurl.com/6k5uuf7 .
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*Note: “In prev. clinical experience with Avastin+PC in NSCLC, patients with ‘squamous’ cancer had a higher risk of experiencing life-threatening or fatal pulmonary bleeding. Squamous cells are a kind of cell that form in the lining of the air ducts in the lung. Because of the risk of bleeding attributed to this population, patients with NSCLC classified as predominantly squamous histology were not `included in the E4599 trial.” http://tinyurl.com/cfk9ao
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ORR% UPDATE HISTORY FOR PH.2/BAVI+PC/NSCLC/INDIA:
2-4-09 PR: “7 of 21 (33%) achieving PR (CR=1)” (after 4 of 6 3wk cycles)
=> 6-3-09 PR: “11 of 21 (52%) achieving PR” (after 6 of 6 3wk cycles)
==> 6-4-10 PR: “21 of 49 (43%) ORR%” (includes 9 non-evaluables)
===> 6-15-11 PR: “21 of 49 (43%) ORR%, MOS=12.4mos”
- - - - - - - - -
NSCLC/India 1st-DOSED: 6-30-08 => 100.1wks a/o 6-1-10
ALL-21-ENROLLED-Stage1: 10-20-08 => 84.1wks a/o 6-1-10 (1.3/wk)
1st-DOSED-Stage2(28): 4-20-09 => 58.1wks a/o 6-1-10
ALL-28-DOSED-Stage2: 10-5-09 => 34.1wks a/o 6-1-10 (1.2/wk)

= = = = = = = = = = = = = PH.2 BAVI DOSING:
Bavi+Doce-2ndLine-BREAST/GA: 6 4wk-cycles of chemo, weekly-bavi (1 prior chemo, but no Doce)
. . . http://clinicaltrials.gov/ct2/show/NCT00669591
Bavi+PC-Frontline-BREAST/India: 6 4wk-cycles of chemo, weekly-bavi (no prior chemo/immuno/rad)
. . . http://clinicaltrials.gov/ct2/show/NCT00669565
Bavi+PC-Frontline-LUNG/India: 6 3wk-cycles of chemo, weekly-bavi (no prior chemo/immuno/rad)
. . . http://clinicaltrials.gov/ct2/show/NCT00687817

ANALYSIS OF RECIST DATA:
• CR (Complete Response), all lesions have disappeared
• PR (Partial Response), shrinkage >30% compared to baseline
• PD (Progressive Disease), >20% increase compared to any assessment
• SD (Stable Disease), an evaluable assessment that is neither CR, PR or PD
• NE (Non-Evaluable), generally study specific

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Sept. 27, 2011 - JMP Securities Healthcare Conf. (NYC)
Peregrine’s CEO Steve King – Slide Capture: http://tinyurl.com/3qqslkb
Webcast replay (14:21): http://www.wsw.com/webcast/jmp14/pphm

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FYI, here are Peregrine’s 3 Currently-Running Ph.2 Bavi+Chemo Randomized Cancer Trials:

G. Phase IIb Bavi+CP vs. Front-Line NSCLC (randomized, unblinded, 'confirmatory')
Protocol: http://clinicaltrials.gov/ct2/show/NCT01160601 (17 U.S. + 9 India + 2 RepGA + 7 RussianFED + 5 Ukraine = 40 as of 8-12-11)
...Also listed in: India's CTRI registry ctri.in#2190 and WHO's registry who.int#1402
...9-8-11: Enrollment complete. http://tinyurl.com/3vv9zfx
...7-14-11/CC: Enrollment was taking longer than expected; have amended protocol; expanding to 30+ sites, expect enroll. comp. "in coming weeks", interim data by Yr-end'11. http://tinyurl.com/6k6y2as
…7-14-10/CC, J.Shan (VP/Clin+RegAffairs): ”This trial is intended to confirm in a randomized setting the results from our Ph.2 signal-seeking NSCLC trial which showed 43% ORR, more than double the generally accepted chemo ORR of under 20% in numerous publications. Favorable results could then lead to an end of Ph.2 meeting with the FDA, with possibly a pivotal Ph/3 trial for front-line lung cancer, our 2nd potential regulatory pathway for bavituximab."

F. Phase IIb Bavi+Doce vs. Refractory NSCLC (randomized, double-blinded, placebo-controlled, n=120, 'registrational')
Protocol: http://clinicaltrials.gov/ct2/show/NCT01138163 (24 U.S. + 15 India + 2 RepGA + 7 RussianFED + 5 Ukraine = 53 as of 8-12-11)
...Also listed in: India's CTRI registry ctri.in#2191 (12 sites a/o 3-20-11)
...10-6-11: Enrollment complete. http://tinyurl.com/3m9re39
...7-14-11/CC: Enrollment was taking longer than expected; have amended protocol; expanding to ~45 sites, expect enroll. comp. "early in Q4/2011", data unblinding 1H'12. http://tinyurl.com/6k6y2as
…3-17-10/Roth, CEO S.King: "We refer to this trial as a Registrational Phase II Study, because we believe that if we have results anywhere near approaching what we saw in the earlier [India] study, it could be a conduit for Accelerated Approval."
...6-4-10: Ph.2b randomized reg. trial Open for enrollment: http://tinyurl.com/25v22qk
……"up to 120 refractory patients at ~30 clinical sites; goal: fully-enroll by mid'11, topline data by y/e'11."

I. Phase II Bavi+GEM vs. Front-Line PANCREATIC (randomized, unblinded)
Protocol: http://www.clinicaltrials.gov/ct2/show/NCT01272791 (21 U.S. Sites as of 10-13-11)
...1-5-11: U.S. Ph.2 randomized trial initiated http://tinyurl.com/26hnuzv