Transcript CytRx (CYTR) Corporate Presentation

Randomized phase 2b trial
comparing first-line treatment with
aldoxorubicin versus doxorubicin in
patients with advanced soft tissue
sarcomas
Sant Chawla, M.D.
Principal Investigator
Director, Sarcoma Oncology Center
Santa Monica, California
Targeting Tumors Using Endogenous
Albumin
Acid-sensitive linker coupled to doxorubicin
binds covalently to circulating albumin in < 5
minutes
Drug
Linker
Albumin
Predetermined
Breaking point


After infusion, linker
forms covalent bond
to cysteine-34 on
albumin
Able to deliver several times more drug because drug is
inactive until released at the tumor
Linker can be used with many types of cancer drugs:
anthracyclines, taxanes, camptothecins, platinums, etc.
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Aldoxorubicin First-line STS Phase 2b
Trial Design
Screened
N=140
14 screen failures
2:1 Randomization
N=123
Aldoxorubicin
350mg/m2
(260mg/m2 dox equiv.)
Every 3wk up to 6 cycles
N=83
3 subjects
randomized but not
dosed
Doxorubicin
75mg/m2
Every 3wk up to 6 cycles
N=40
CT Scans every 6 weeks
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Patient Characteristics
Characteristics
Aldoxorubicin
Doxorubicin
83
40
Age, median (range)
54.0 (21-77)
54.0 (23-77)
Male / Female, n (%)
46 / 54
45 / 55
74
80
1
2.5
Asian
19
15
Other
6
2.5
96
92
4
8
6 (1-6)
4 (1-6)
N
Race, n (%)
Caucasian
Black or African American
ECOG, n (%)
0-1
2
Completed Cycles, median (range)
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Disease Characteristics
Histopathology
Aldoxorubicin
N = 83
Doxorubicin
N = 40
Leiomyosarcoma, (%)
34
35
Liposarcoma, (%)
16
15
Fibrosarcoma, (%)
14
10
6
10
30
30
(as determined by investigator)
Synovial sarcoma, (%)
Others, (%)
Presented by: Sant Chawla, M.D.
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Primary Endpoint: PFS
All Subjects
Intent-to-treat
P Value
Scans Read by Investigator
Aldoxorubicin
8.4 months
Doxorubicin
4.7 months
Improvement over dox
Hazard ratio
P=0.0004
3.7 mos. (79%)
0.419 (0.25-0.69)
P=0.0007
Scans Read by Blinded Central Lab
Aldoxorubicin
5.7 months
Doxorubicin
2.8 months
Improvement over dox
Hazard ratio
P=0.014
2.9 mos. (104%)
0.584 (0.37-0.93)
P=0.024
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K-M Curve - Investigator Assessment
3.7 month improvement
HR: 0.419, p=0.0007
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K-M Curve – Central Lab Assessment
2.9 month improvement
HR: 0.584, p=0.024
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PFS at 6 Months Results
All Subjects
Intent-to-Treat
P Value
Scans Read by Investigator
Aldoxorubicin
68.1%
Doxorubicin
36.6%
Improvement over dox
P=0.002
86.1%
Scans Read by Blinded Central Lab
Aldoxorubicin
45.7%
Doxorubicin
22.9%
Improvement over dox
P=0.02
99.6%
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Overall Response Rate Results
Aldoxorubicin
Doxorubicin
2.4%
0%
Partial Response
19.3%
5.0%
Overall Response Rate
21.7%
5.0%
0%
0%
Partial Response
23.8%
0%
Overall Response Rate
23.8%
0%
Scans Read by Investigator
Complete Response
Scans Read by Central Lab
Complete Response
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Waterfall Plot - Investigator
Aldoxorubicin
64.5% had tumor shrinkage
Doxorubicin
41.2% had tumor shrinkage
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Waterfall Plot – Blinded Central Lab
Aldoxorubicin
60.8% had tumor shrinkage
Doxorubicin
39.4% had tumor shrinkage
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Overall Survival - Preliminary
 Too early to determine OS due to prolonged survival of patients
in study.
 As of September 15, 2014:
% Deaths
% Lost to
F/U
% Still
Followed
Aldoxorubicin
42
19
39
Doxorubicin
55
18
27
 Higher % deaths and lower % still being followed in doxorubicintreated subjects.
 Lower % deaths and higher % still being followed in
aldoxorubicin-treated subjects.
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Comparison to Current STS
Treatments
CytRx
Phase 2b
Investigator assessed
N
Age
PFS (months)
Aldox
Dox
Dox+ ifos
Dox
83
40
215
217
54 (21-77)
54 (23-77)
48 (18-60)
47 (18-63)
8.4
4.7
7.4
4.6
P value
OS (months)
EORTC
Phase 3
Dox vs. dox+ ifosfamide
0.0004
NA
0.003
NA
14.3
P value
ORR
12.8
0.076
21.7%
5.0%
26.5%
13.6%
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Comparison to TH-302 + Doxorubicin
CytRx
Phase 2b
Investigator assessed
Phase 2
TH-302 + Doxorubicin
Investigator assessed
Aldoxorubicin
(max. 6 doses)
TH-302 + Doxorubicin
N
83
91
Median PFS
(months)
8.4
6.5
68%
58%
21.7%
36%
(30% without maintenance)
PFS-6 months
ORR
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Grade 3/4 TEAEs
Aldoxorubicin
Doxorubicin
N=83
N=40
(%)
(%)
40
20
Neutropenic fever
15.7
17.5
Thrombocytopenia
6
5
13.2
20
7.2
0
10.8
2.5
6.0
5.0
Event
Neutropenia
Anemia
Nausea/vomiting
Mucositis
Fatigue/weakness
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Minimal Alopecia Even After 8 Cycles
of Aldoxorubicin
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Cardiac Evaluation
Aldoxorubicin
Doxorubicin
Median Cumulative Dose (mg/m2)
[range]
2,100*
[350-2,800]
300*
[75-450]
% subjects with ≥15% decrease in
LVEF
8%
34%
% subjects with ≥15% increase in
LVEF
15%
3%
% subjects with ≤45% of expected
value
0%
5.7%
*Maximum of 6 cycles allowed per protocol
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Conclusions
 Aldoxorubicin significantly increases PFS, PFS at 6 months and
ORR compared to doxorubicin therapy for first line STS.
 Grade 3 or 4 neutropenia, mucositis and nausea/vomiting are
higher in aldoxorubicin-treated patients but are not treatment
limiting.
 The aldoxorubicin patients received more than 5 times the
cumulative amount of doxorubicin in this study than the
doxorubicin patients without any evidence of clinically relevant
decreased LVEF, and in more instances an increase in LVEF,
either by MUGA or echocardiogram.
 A phase 3 pivotal trial under a SPA is ongoing for
relapsed/refractory STS.
Presented by: Sant Chawla, M.D.
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Phase 3 Trial Design: 2nd-line STS
Soft tissue sarcoma patients that have relapsed or are
refractory to prior chemotherapy
1:1 Randomization
N=400
Aldoxorubicin
350mg/m2
(260mg/m2 dox equiv.)
Every 3weeks until
disease progression
N=200
Physicians Choice:
Doxorubicin
Dacarbazine
Ifosfamide
Gemcitabine+docetaxel
Pazopanib
N=200
Primary Endpoint: PFS
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Aldoxorubicin + Ifosfamide Study
 A Single Center, Open-Label Phase 1b/2 Study to Investigate the
Preliminary Safety and Activity of Aldoxorubicin plus Ifosfamide/Mesna
in Subjects with Metastatic, Locally Advanced, or Unresectable Soft
Tissue Sarcoma
 Aldoxorubicin administered at either 170, 250 or 350 mg/m2 (125, 185
and 260 mg/m2 doxorubicin equivalents) intravenously on Day 1 every
28 days plus 1 gm/m2 ifosfamide by continuous intravenous infusion for
14 days via a portable/ambulatory infusion pump every 28 days until
disease progression, unacceptable toxicity or withdrawal of consent.
 Tumor response will be monitored every 8 weeks from Cycle 1-Day 1
through week 33, and then every 12 weeks until disease progression
using the RECIST 1.1 criteria.
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