Trial Outcomes & Findings for ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC) (NCT NCT02325557)

Last Updated: 2024-04-02

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Adverse events with onset dates on or after the first dose of study medication and within 30 days following the last dose of study medication were considered "treatment emergent".

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

50 participants

Primary outcome timeframe

From first dose up to 30 days after last dose (maximum duration: 108 weeks)

Results posted on

2024-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	Part A: ADXS31-142 1x10^9 CFU Participants received ADXS31-142 1 × 10\^9 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU Participants received ADXS31-142 5 × 10\^9 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 1×10^10 CFU Participants received ADXS31-142 1 × 10\^10 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 1×10^9 CFU + Pembrolizumab Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Overall Study STARTED	10	1	2	37
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	10	1	2	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: ADXS31-142 1x10^9 CFU Participants received ADXS31-142 1 × 10\^9 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU Participants received ADXS31-142 5 × 10\^9 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 1×10^10 CFU Participants received ADXS31-142 1 × 10\^10 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 1×10^9 CFU + Pembrolizumab Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Overall Study Progressive disease	1	0	0	0
Overall Study Withdrawal by Subject	4	0	0	15
Overall Study Death	5	1	1	16
Overall Study Lost to Follow-up	0	0	1	1
Overall Study Other	0	0	0	5

Baseline Characteristics

ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: ADXS31-142 1×10^9 CFU n=10 Participants Participants received ADXS31-142 1 × 10\^9 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU n=1 Participants Participants received ADXS31-142 5 × 10\^9 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 1×10^10 CFU n=2 Participants Participants received ADXS31-142 1 × 10\^10 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 + Pembrolizumab n=37 Participants Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.	Total n=50 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	0 Participants n=7 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	11 Participants n=7 Participants	14 Participants n=31 Participants
Age, Categorical >=65 years	7 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	26 Participants n=7 Participants	36 Participants n=31 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Sex: Female, Male Male	10 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	37 Participants n=7 Participants	50 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	36 Participants n=7 Participants	49 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 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	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	7 Participants n=7 Participants	7 Participants n=31 Participants
Race (NIH/OMB) White	9 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	30 Participants n=7 Participants	42 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants

PRIMARY outcome

Timeframe: From first dose up to 30 days after last dose (maximum duration: 108 weeks)

Population: The All Treated Population included all participants who received at least one dose of ADXS31-142 or pembrolizumab.

Outcome measures

Outcome measures
Measure	Part A: ADXS31-142 1×10^9 CFU n=10 Participants Participants received ADXS31-142 1 × 10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU n=1 Participants Participants received ADXS31-142 5×10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	ADXS31-142 1×10^10 CFU n=2 Participants Participants received ADXS31-142 1×10\^10 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 + Pembrolizumab n=37 Participants Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Number of Participants With Treatment-Emergent Adverse Events	10 Participants	1 Participants	2 Participants	37 Participants

SECONDARY outcome

Timeframe: From screening until progression or death (maximum duration: 104 weeks)

Population: The ORR Evaluable Population included all participants who received at least one dose of ADXS31-142 or pembrolizumab and who had at least one post-baseline radiologic tumor response assessment (CR, PR, stable disease \[SD\], or progressive disease \[PD\]) with evaluable results.

The objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 was defined as the number of participants with objective evidence of radiologic complete response (CR: disappearance of all target lesions) and partial response (PR: at least a 30% decrease in the sum of the longest diameters of target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions) as determined from investigator response assessments. Disease Control Rates are based upon confirmed events only.

Outcome measures

Outcome measures
Measure	Part A: ADXS31-142 1×10^9 CFU n=7 Participants Participants received ADXS31-142 1 × 10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU n=1 Participants Participants received ADXS31-142 5×10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	ADXS31-142 1×10^10 CFU Participants received ADXS31-142 1×10\^10 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 + Pembrolizumab n=29 Participants Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Objective Response Rate (ORR)	0 participants	0 participants	—	0 participants

SECONDARY outcome

Timeframe: From screening until progression or death (maximum duration: 104 weeks)

Population: Participants in the ORR Evaluable Population were analyzed. The ORR Evaluable Population included all participants who received at least one dose of ADXS31-142 or pembrolizumab and who had at least one post-baseline radiologic tumor response assessment (CR, PR, stable disease \[SD\], or progressive disease \[PD\]) with evaluable results.

The ORR according to irRECIST was defined as the number of participants with objective evidence of radiologic immune-related CR (irCR: Disappearance of all target lesions) and immune-related PR (irPR: At least 30% decrease in tumor burden compared with baseline) as determined from investigator response assessments.

Outcome measures

Outcome measures
Measure	Part A: ADXS31-142 1×10^9 CFU n=7 Participants Participants received ADXS31-142 1 × 10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU n=1 Participants Participants received ADXS31-142 5×10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	ADXS31-142 1×10^10 CFU Participants received ADXS31-142 1×10\^10 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 + Pembrolizumab n=28 Participants Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Objective Response Rate According to Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)	0 participants	0 participants	—	0 participants

SECONDARY outcome

Timeframe: From screening until progression or death (maximum duration: 104 weeks)

Population: All treated patients population

Progression-free survival (PFS) was defined as the time from randomization until objective tumor progression based on response evaluation criteria in solid tumors (RECIST) version 1.1 or death. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions. Participants who had not experienced disease progression or who were still alive at the time of evaluation were censored for the analysis. The PFS was estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Part A: ADXS31-142 1×10^9 CFU n=10 Participants Participants received ADXS31-142 1 × 10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU n=1 Participants Participants received ADXS31-142 5×10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	ADXS31-142 1×10^10 CFU n=2 Participants Participants received ADXS31-142 1×10\^10 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 + Pembrolizumab n=37 Participants Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Progression-free Survival, Assessed by RECIST Version 1.1	2.2 Months Interval 0.8 to lack of events due to censoring	NA Months lack of events due to censoring	NA Months lack of events due to censoring	5.3 Months Interval 2.1 to 7.9

SECONDARY outcome

Timeframe: From screening until progression or death (maximum duration: 104 weeks)

Overall survival is defined as the time from the date of start of study treatment until death due to any cause. Any participant not died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The OS was estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Part A: ADXS31-142 1×10^9 CFU n=10 Participants Participants received ADXS31-142 1 × 10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part A: ADXS31-142 5×10^9 CFU n=1 Participants Participants received ADXS31-142 5×10\^9 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	ADXS31-142 1×10^10 CFU n=2 Participants Participants received ADXS31-142 1×10\^10 CFU, IV Q3W in a 12-week cycle for up to 24 months or until disease progression or discontinuation.	Part B: ADXS31-142 + Pembrolizumab n=37 Participants Participants received ADXS31-142 1 × 10\^9 CFU IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.
Overall Survival	7.8 Months Interval 1.3 to Sample size is too small. Lack of events due to censoring	18.5 Months Sample size too small	7.8 Months Sample size is too small. Lack of events due to censoring	33.7 Months Interval 15.4 to The upper 95% CI cannot be calculated due to insufficient number of events in the tested time frame

Adverse Events

Part A: ADXS31-142 1×10^9 CFU

Serious events: 4 serious events

Other events: 10 other events

Deaths: 5 deaths

Part A: ADXS31-142 5×10^9 CFU

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Part A: ADXS31-142 1×10^10 CFU

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

Part B: ADXS31-142 + Pembrolizumab

Serious events: 22 serious events

Other events: 37 other events

Deaths: 16 deaths

Serious adverse events

Other adverse events

Additional Information

Sumitra Sheeri

Advaxis, Inc.

Phone: 609-423-2528

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator shall seek the Sponsor's written approval for study results publication which shall not be unreasonably withheld. Such publication by Institution and/or Investigator may be no earlier than after a cooperative publication has been published with Sponsor or 1 year from date of completion or termination of the Study \& only after review and comment by Sponsor. Institution agrees to provide Sponsor a copy of proposed publication at least 60 days prior to submission to a publisher.
Publication restrictions are in place

Restriction type: OTHER