Trial Outcomes & Findings for Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer (NCT NCT02362451)

Last Updated: 2022-03-18

Results Overview

PSA Doubling Time (PSADT) and slope log (PSA) were calculated at every study visit using the PSADT Memorial Sloane Kettering nomogram. The values were calculated to demonstrate the rate of rise of PSA, expressed as the velocity in nanograms/mL/year, or the PSA doubling time, in months or years. PSA is a tumor marker for prostate cancer and after surgery (undetectable - e.g. \<0.2 ng/mL) or radiation PSA should fall to a very low level when the disease is effectively treated. When PSA increases (\>2.0 ng/mL) after surgery or radiation that could mean recurrence of the disease. If prostate cancer is growing slower or shrinking after the treatment, PSADT can be longer while PSA slope log is shorter as tumor will make less PSA.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

One year pre-enrollment; weeks 3-24, and 3 - 48 post vaccine

Results posted on

2022-03-18

Participant Flow

No participants were enrolled to the Arm 3 placebo group.

Participant milestones

Participant milestones
Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24
Overall Study STARTED	6	1
Overall Study COMPLETED	2	0
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24
Overall Study Withdrawal by Subject	0	1
Overall Study Lack of Efficacy	2	0
Overall Study Progression	1	0
Overall Study Participant chose other therapy.	1	0

Baseline Characteristics

Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=6 Participants Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=1 Participants Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Age, Categorical >=65 years	5 Participants n=99 Participants	0 Participants n=107 Participants	5 Participants n=206 Participants
Age, Continuous	68.73 years STANDARD_DEVIATION 3.5 • n=99 Participants	57.2 years STANDARD_DEVIATION 0 • n=107 Participants	67.09 years STANDARD_DEVIATION 5.41 • n=206 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	1 Participants n=107 Participants	7 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=99 Participants	1 Participants n=107 Participants	7 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	6 Participants n=99 Participants	1 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	6 participants n=99 Participants	1 participants n=107 Participants	7 participants n=206 Participants

PRIMARY outcome

Timeframe: One year pre-enrollment; weeks 3-24, and 3 - 48 post vaccine

Population: One participant in the lead in group had no data for week 48 due to other treatment, thus data could not be used. And one participant in the active group had no data for week 3-24 and 3-48 due to other treatment, thus data could not be used.

Outcome measures

Outcome measures
Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=6 Participants Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=1 Participants Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24
Change in the Slope Log of Prostate-specific Antigen Pre vs Post Treatment Pre treatment	0.07 slope log Interval 0.05 to 0.19	0.05 slope log Interval 0.0 to 0.05
Change in the Slope Log of Prostate-specific Antigen Pre vs Post Treatment Weeks 3-24	0.08 slope log Interval -0.01 to 0.21	—
Change in the Slope Log of Prostate-specific Antigen Pre vs Post Treatment Weeks 3-48	0.06 slope log Interval 0.01 to 0.07	—

SECONDARY outcome

Timeframe: Week 96 after initial vaccination

PFS is defined as the duration of time from start of vaccine treatment to time of progression or death. Given the study population in biochemically recurrent prostate cancer, progression is defined as 1)"radiographic progression" by computed tomography (CT) or bone scan, 2) prostate-specific antigen doubling time (PSADT) that is 3 month or shorter, 3) PSADT decrease 50% or more compared to enrollment PSADT.

Outcome measures

Outcome measures
Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=6 Participants Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=1 Participants Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24
Progression Free Survival (PFS)	96 Weeks Interval 48.0 to 96.0	NA Weeks The median and full range is not available for the 1 participant in the Active group. The participant was censored at that time point because he came off study, not that he progressed.\]

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.

Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=6 Participants Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=1 Participants Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24
Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	6 Participants	1 Participants

Adverse Events

1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Hoyoung Maeng

National Cancer Institute

Phone: 240-781-3253

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=6 participants at risk Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24	2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment n=1 participants at risk Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Musculoskeletal and connective tissue disorders Bone pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Eye disorders Cataract	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Gastrointestinal disorders Chills	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Investigations Creatinine increased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
General disorders Edema limbs	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Injury, poisoning and procedural complications Fall	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
General disorders Fatigue	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
General disorders Flu like symptoms	33.3% 2/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Nervous system disorders Headache	33.3% 2/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Vascular disorders Hot flashes	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Vascular disorders Hypertension	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
General disorders Injection site reaction	100.0% 6/6 • Number of events 71 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Blood and lymphatic system disorders Lymph node pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Investigations Lymphocyte count decreased	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
General disorders Malaise	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, Muscle aches/ left thigh	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Gastrointestinal disorders Nausea	0.00% 0/6 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Respiratory, thoracic and mediastinal disorders Postnasal drip	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, lesion on scalp	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, small nodule behind right ear	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Infections and infestations Upper respiratory infection	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Infections and infestations Urinary tract infection	0.00% 0/6 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 54 months and 13 days for cohort 1 and 5 months and 9 days for cohort 2.