Avid Bioservices Inc (CDMO)

[cjgaddy]

ASCO 6-1-09, oral pres. #3005: updated prelim. data from the Ph2 Bavi+Doce/MBC/GA trial ( abstract: http://tinyurl.com/qem2wg ). Obviously, we’re moving from ~24wk data (10-21-08 PR) to a FULL-YR’s DATA on all Stage1 patients (14 evaluables), and probably ~12wk data on the 1st ~16* or so Stage2 patients.

*MY EST. OF ~16 STAGE2’S: Stage2 took approx. 28wks (10-21-08 – 5-4-09) to enroll 31 patients, or about 1.1 per week. Back up 14wks from ASCO-time (~5-26-09), to 2-17-09, when ~16 patients would have been enrolled in S2. Those 16 patients will have received 2 (4wk) Bavi+Doce cycles, had their 8wk/initial & 12wk/confirmation scans, and 2 weeks to assemble data. …Like I said, just an estimate.

Review of this trial’s objectives…

PH.2 BAVI+DOCETAXEL VS. ADV./MET. BREAST CANCER - GA:
http://clinicaltrials.gov/ct2/show/NCT00669591 (15+31=46)
PRIMARY OBJECTIVE:
• Overall response rate (ORR)
SECONDARY OBJECTIVES:
• Time to Tumor Progression (TTP)
• Duration of Response (DOR)
• Overall Survival (OS)
• Safety

1st-DOSED: 2-12-08 => 67.0wks a/o 5-26-09
ALL-15-DOSED-Stage1: 4-29-08 => 56.0wks a/o 5-26-09
1st-Screened-Stage2(31): 10-21-08 => 31.0wks a/o 5-26-09
ALL-31-DOSED-Stage2: 5-4-09 => 3.1wks a/o 5-26-09

Definitions…
OBJECTIVE RESPONSE RATE
The proportion of treated people in whom a complete or partial response is observed.

TTP (TIME TO PROGRESSION) & PFS (PROGRESSION-FREE SURVIVAL)
TTP & PFS have served as primary endpoints for drug approval. TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths. PFS is defined as the time from randomization until objective tumor progression or death. The precise definition of tumor progression is important and should be carefully detailed in the protocol.
TTP vs. PFS:
Compared with TTP, PFS is the preferred regulatory endpoint. PFS includes deaths and thus can be a better correlate to overall survival. In TTP analysis, deaths are censored, either at the time of death or at an earlier visit representing informative censoring (nonrandom pattern of loss from the study). PFS assumes patient deaths are randomly related to tumor progression. However, in situations where the majority of deaths are unrelated to cancer, TTP can be an acceptable endpoint.
http://www.fda.gov/CBER/gdlns/clintrialend.htm

DURATION OF RESPONSE
The length of time after treatment that a patient remains in complete or partial remission.

OVERALL SURVIVAL
Denotes the percentage of individuals in the group who are likely to be alive after a particular duration of time. At a basic level, the overall survival is representative of cure rates.

RECIST Criteria:
1. COMPLETE RESPONSE (CR) = 100% reduction
2. PARTIAL RESPONSE (PR) = 30-99% reduction
. . . [OBJECTIVE RESPONSE (OR) = CR + PR = 30-100% red.]
3. STABLE DISEASE (SD) = 29% reduction – 19% increase
4. PROGRESSIVE DISEASE (PD) = 20% increase or more
**ALSO: "to be assigned to SD or PR, patients cannot have the appearance of any new lesions."
http://ctep.cancer.gov/guidelines/recist.html

RECIST scanning guidelines: everybody gets scanned every 8 weeks, except when a patient goes to PR/CR (at any point), he/she gets a one-time “confirmation” scan 4 weeks later (and then goes back to every 8 weeks).
So, that translates to 4 situations depending on the 1st 8-wk scan:
1. Patient tests SD after 1st 8-week scan, and stays that way: 8, 16, 24, 32. . .
2. Patient tests PR after 1st 8-week scan, and stays that way: 8, 12, 20, 28. . .
3. Patient is SD at 8wks, but upgrades to PR at wk16: 8, 16, 20, 28. . .
4. Patient is PR at 8 weeks, but slides back to SD at wk12: 8, 12, 20, 28. . .

= = = = = = = = = = =
May29-June2: “45th ASCO Annual Meeting”, Orlando http://tinyurl.com/pkbq59
...1) June1 10:30am #3005: Ph.2 Bavi+Doce/MBC/GA updated prelim. data - oral presentation
. . . . . . Abstract #3005, released 5-14-09: http://tinyurl.com/qem2wg
...2) June1 1-5pm #1080: USA Ph.1 Bavi-Monotherapy updated prelim. data (poster)
. . . . . . Abstract #1080, released 5-14-09: http://tinyurl.com/pdpok5

= = = = = = = = = = =
C. Phase II Bavi+Docetaxel vs. Adv./Met. Breast Cancer in E.EUR.(Georgia):
Georgia Ministry of Health protocol (init=1-2008): http://clinicaltrials.gov/ct2/show/NCT00669591
5-4-09: Stage2 Enrollment Complete (15+31=46 total): http://tinyurl.com/cp737p
…”Prelim. data (updated!) accepted for oral-presentation at ASCO’09 May29-June2.”
10-21-08: “10 of 14 (71%) evaluables achieved an objective tumor response.” http://tinyurl.com/6qx4gp
…Mojo’s early comp of Bavi+Doce Ph.2 vs. Avastin+Chemo trials - PFS% chart: http://tinyurl.com/5rergk
9-9-08 SK: “We have now seen addl. patients with tumor responses, with 9 of the 14 evaluables (64%) having achieved PR.” http://tinyurl.com/5q9phf
7-2-08: Ph.2 Bavi+Doce/Breast update. http://tinyurl.com/5tvfhy
…”At 8wks (of 24wk combo regimen), 100% of [1st 14] evaluables showing OR/SD; 7 of 14 (50%) achieving PR”
6-2-08: ASCO/2008 Ph.2 Bavi+Doce/Breast Update: http://tinyurl.com/5xll6f
…”At 8wks (of 24wk combo regimen), 100% of [1st 11] evaluables showing OR/SD; 5 of 11 (45%) achieving PR”
4-29-08: 1st-15 enrolled http://tinyurl.com/47o85x , 2-12-08: 1st-dosed http://tinyurl.com/36c28s , 1-29-08 Enroll. begins http://tinyurl.com/22ecb2
11-16-07: Ph.2 protocol approved. “Patient Enrollment expected by early 2008.” http://tinyurl.com/3aavzh
10-22-07: Protocol Submitted to Ministry of Health, Rep. of Georgia: http://tinyurl.com/2xjjgp
…”15 patients with MBC initially; exp. to 46 if promising results are observed in the 1st cohort; primary obj: assess overall response.”