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TITAN: apalutamide + ADT versus placebo plus
ADT in mHSPC
§
The original study protocol in June 2015 included only low volume patients. The protocol was amended in
April 2016 to now include both low-volume and high-volume mHSPC patients.
TITAN clinical trial design
Patient Characteristics
•
All-comers mHSPC
•
All subjects could have received ≤6
months of ADT prior to
randomization.
•
For localized prostate cancer,
subjects may have received ≤3
years total of ADT and all other
forms of prior therapies including
radiation therapy, prostatectomy,
lymph node dissection, and
systemic therapies as long as all
such therapies were completed ≥1
year prior to randomization.
R
A
N
D
O
M
I
Z
E
D
1:1
(N=1000)
Apalutamide
240 mg/d
+
ADT
Placebo
+
ADT
Primary End Point
•
rPFS
•
OS
Secondary End Points
•
Time to skeletal-related event
•
Time to chronic opioid use
•
Time to initiation of cytotoxic
chemotherapy
•
Time to pain progression
28-day treatment cycles until disease progression or toxicity
Key inclusion criteria:
Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion
must have confirmation of bone metastasis by CT or MRI. Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of
6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable
disease or better, by investigator assessment of imaging and PSA, prior to randomization
Phase 3, randomised, double-blind, placebo-controlled registration trial
TITAN: apalutamide + ADT versus placebo plus
ADT in mHSPC
§
The original study protocol in June 2015 included only low volume patients. The protocol was amended in
April 2016 to now include both low-volume and high-volume mHSPC patients.
TITAN clinical trial design
Patient Characteristics
•
All-comers mHSPC
•
All subjects could have received ≤6
months of ADT prior to
randomization.
•
For localized prostate cancer,
subjects may have received ≤3
years total of ADT and all other
forms of prior therapies including
radiation therapy, prostatectomy,
lymph node dissection, and
systemic therapies as long as all
such therapies were completed ≥1
year prior to randomization.
R
A
N
D
O
M
I
Z
E
D
1:1
(N=1000)
Apalutamide
240 mg/d
+
ADT
Placebo
+
ADT
Primary End Point
•
rPFS
•
OS
Secondary End Points
•
Time to skeletal-related event
•
Time to chronic opioid use
•
Time to initiation of cytotoxic
chemotherapy
•
Time to pain progression
28-day treatment cycles until disease progression or toxicity
FPI Dec 2015 and first approval (US) expected Nov 2021. Exploratory biomarkers predictive of apalutamide response
and resistance (e.g. AR
F876L
) will also be studied
Key inclusion criteria:
Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion
must have confirmation of bone metastasis by CT or MRI. Participants who received doc taxel t eatment must m et he following criteria: a) Received a maximum of
6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable
disease or better, by investigator assessment of imaging and PSA, prior to randomization
Phase 3, randomised, double-blind, placebo-controlled registration trial
Clinicaltrials.gov: NCT02489318; TITAN Clinical Study Protoc