Transcript DCVAC/LuCa

POSSIBLE SYNERGIES BETWEEN WESTERN
AND TRADITIONAL CHINESE MEDICINES
ACADEMIC ROUNDTABLE ORGANIZED UNDER THE AUSPICES OF
THE CZECH MINISTRY OF HEALTH
ROUNDTABLE 2
- “TCM AS SCIENCE AND EVIDENCE-BASED CLINICAL PRACTICE”
Prof. Radek Špíšek, MD, PhD, Chief Scientist, SOTIO a.s.
FEBRUARY 23, 2017
Cancer immunotherapy- breakthrough of the year
DCVAC/LuCa
1• Patient visits
leukapheretic center
where his blood is used
to…
2• … separate monocytes
and grow immature DCs
3• Tumor cell line1 is
prepared and killed by
immunogenic death
4
4• Immature DCs are mixed
with killed tumor cells
5• Mature DCs are prepared
3
All processes need state of the art scheduling and logistics
1 Acquired from ATTC
6• ~18 doses of
DCVAC/LuCaare
produced and frozen in
liquid nitrogen
7
• Patient receives vaccine
on an ongoing basis
(1 shot per month)
DC- T cell interaction in the lymph nodes
High CRT expression correlates with better overall survival in
NSCLC
•
Heterogenous distribution of CRT expression among different patient´s tumors independent on
the histological origin of the tissue and administered chemotherapy
•
CRT expression is associated with better prognosis – the median of CRTLo group was 28
months compared to CRTHi groups with 100 months
Fucikova, Cancer Research, 2016
Fucikova, Blood 2016
SOTIO DCVAC Ongoing Program Prague / Boston
Product
Technology
DCVAC/PCa
DC
immunotherapy
DCVAC/OvCa
DCVAC/LuCa
DC
immunotherapy
DC
immunotherapy
Company
Pre-clinical
Phase I
Phase II
Phase III
VIABLE study
Multiple trials in different settings
Multiple trials in different settings
One trial in NSCLC Stage IV
6
GMP facility, Beijing: 18 clean boxes
Manufacturing for China
Huilongseng International Enterprise Incubator, Beijing, Yizhuang
Chinese ongoing Hospital Research Projects
Project size
Patients
Enrolled
(2017-JAN-20)
Beijing Tongren Hospital
A Safety Study of DCVAC/PCa in Men
with Metastatic Castration Resistant Metastatic Castration
Prostate Cancer Eligible for 1st Line Resistant Prostate Cancer
Chemotherapy
10
7
China-Japan Friendship
Hospital
A Study on DCVAC/PCa
Immunotherapy in Men with
Asymptomatic or Minimal
Symptomatic Metastatic Castration
Resistant Prostate Cancer
Asymptomatic or Minimal
Symptomatic Metastatic
Castration Resistant
Prostate Cancer
10
8
Metastatic Non-small Cell
Lung Cancer
13
13
Hospital
Project Name
Safety and Efficacy Study of
China-Japan Friendship DCVAC/LuCa Concurrent
Hospital
Chemotherapy in Metastatic Nonsmall Cell Lung Cancer
Indication
8
ILU03: Treatments
• SoC chemotherapy
• Investigators can choose from the following SoC regimens:
• paclitaxel/carboplatin administered on Day 1 q3 weeks
• gemcitabine/cisplatin administered on Day 1 (gem. also on Day 8) q3
•
•
•
weeks
• pemetrexed/cisplatin administered on Day 1 q3 weeks
• pemetrexed/carboplatin on Day 1 q3 weeks
Maintenance treatment possible with pemetrexed monotherapy
DCVAC/LuCa
• Administered from the 2nd cycle of SoC, initially in a 3-week cycle (5 times)
and then in a 6-week cycle schedule (for the remainder of the treatment)
• Up to 15 doses can be administered, but 10 delivered doses would be
acceptable
Shenqi Fuzheng infusion
• Shenqi Fuzheng infusion should be administered 3 days before each
DCVAC/LuCa administration and until a total of 14 daily doses have been
administered
• The Shenqi Fuzheng infusion schedule is applicable during both 3-week
and 6-week DCVAC/LuCa administration schedules.
SOTIO - CONFIDENTIAL
9
ILU03: A single-arm phase II study to evaluate efficacy, safety, and
immune response of first-line treatment with Shenqi Fuzheng
infusion, DCVAC/LuCa, and standard of care chemotherapy in
patients with recurrent metastatic or advanced (stage IIIB or IV)
non-small cell lung cancer
•
•
Combining platinum-based chemotherapy with Chinese medicinal herbs (e.g.,
Shenqi Fuzheng infusion) for the treatment of advanced NSCLC may improve
tumor response and performance status, as well as reduce chemotherapy
toxicity.*
The traditional Chinese medicine (TCM) tested in this study, Shenqi Fuzheng
infusion, is concocted from two kinds of Chinese medicinal herbs: Radix
Astragali (root of Astragalus propinquus; Chinese name: huangqi) and Radix
Codonopsis (root of Codonopsis pilosula; Chinese name: dangshen), approved
by the State Food and Drug Administration of the People’s Republic of China in
1999 primarily as an antitumor injection to be manufactured and marketed in
China.*
* Dong J, Su S-Y, Wang M-Y, Zhan Z. Shenqi fuzheng, an injection concocted from Chinese medicinal herbs, combined with platinum-based
chemotherapy for advanced non-small cell lung cancer: a systematic review. Journal of experimental & clinical cancer research: CR. 2010;29.
SOTIO - CONFIDENTIAL
10
ILU03: A single-arm phase II study to evaluate efficacy, safety, and
immune response of first-line treatment with Shenqi Fuzheng
infusion, DCVAC/LuCa, and standard of care chemotherapy in
patients with recurrent metastatic or advanced (stage IIIB or IV)
non-small cell lung cancer
•
•
We hypothesize that immunization with DCVAC/LuCa might induce the
effector cells of the immune system to infiltrate tumors. The resulting
immune reaction may lead to tumor mass reduction.
Addition of Shenqi Fuzheng infusion to DCVAC/LuCa and SoC
chemotherapy may reduce the toxicity of chemotherapy and enhance
the anti-tumor immune responses
SOTIO - CONFIDENTIAL
11
Patients treated with combination of DCVAC/LuCa, TCM,
and Chemotherapy
•
•
•
Median PFS is 12.6 months
•
[expected median PFS 5.0-6.5 months]
Median survival is not reached with only 3 events and 6
censored pts
•
median follow-up in surviving patients = 18.8 months
•
[expected median survival 9.0-17.0 months]
1 year survival is currently 89% and 18 months survival is
currently 67%
•
[expected 1 year survival 60-65%]
SOTIO - CONFIDENTIAL
12
China Clinical Studies: ILU02 and ILU03
Hospital
Study Name
ID
A randomized phase II study to evaluate
efficacy and safety of DCVAC/LuCa added to
Shanghai
chemotherapy with carboplatin and
ILU02
Chest Hospital pemetrexed vs chemotherapy alone in
patients with stage IV non-small cell lung
cancer
A single-arm phase II study to evaluate
efficacy, safety, and immune response
China-Japan of first-line treatment with Shenqi Fuzheng
Friendship
infusion, DCVAC/LuCa, and standard of care ILU03
Hospital
chemotherapy in patients with recurrent
metastatic or advanced (stage IIIB or IV) nonsmall cell lung cancer
Setup
Indication
Size
Patients
Enrolled
Phase II
stage IV non-small cell
lung cancer
70
36
(2017-JAN-20)
stage IIIB or IV nonPhase II
small cell lung cancer
48
1
(2017-JAN-20)
13