CancerPhase 1/2NCT02325557
ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC)
A Phase 1/2 study testing ADXS31-142 and Pembrolizumab in people with Cancer and Prostate Cancer, run by Advaxis, Inc. at 8 sites in United States.
Trial summary
A Phase 1/2 multicenter, dose determining, open-label study of ADXS31-142 monotherapy and a combination of ADXS31-142 and pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer. Part A will be dose-determining part of ADXS31-142 monotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Cancer, Prostate Cancer
- What is being tested?
- ADXS31-142 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 8 sitesUnited States
- Study dates
- 4 Jun 2015to 22 Jan 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have progressive mCRPC, on androgen deprivation therapy, based on at least one of the following criteria:
- Prostate-specific antigen (PSA) progression, defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval with a minimum PSA of 2 ng/mL.
- Progression of bi-dimensionally measurable soft tissue (nodal metastasis) assessed within 1 month prior to registration by computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis.
- Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan.
- Has discontinued antiandrogens (bicalutamide, nilutamide) >6 weeks and enzalutamide >4 weeks prior to Day 1 of trial treatment
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
Who cannot join
- Received more than 3 prior systemic treatment regimens with chemotherapy, hormonal, or immunotherapy in the metastatic setting or received more than 1 prior chemotherapeutic regimen in the metastatic setting
- Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., Grade ≤1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., Grade ≤1 or at baseline) from adverse events due to a previously administered agent.
- Has received prior therapy with an anti-programmed cell death protein-1 (PD-1), anti-programmed death-ligand-1 (PD-L1), or anti-Programmed death-ligand-2 (PD-L2) agent or if the participant has previously participated in a Merck MK-3475 clinical trial.
- Has a contraindication to administration of ampicillin or trimethoprim/ sulfamethoxazole.
- Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants, and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Colorado Health Sciences Center (UCHSC)
Aurora, Colorado
Study site
New Brunswick, New Jersey
Recrutiing
Philadelphia, Pennsylvania
Site
Philadelphia, Pennsylvania
Recruiting
Providence, Rhode Island
Recruiting
Rockville, Maryland
Recruiting
San Francisco, California
Recruiting
Towson, Maryland
About this study
Official title: A Phase 1-2 Dose-Escalation and Safety Study of ADXS31-142 Alone and of ADXS31-142 in Combination With Pembrolizumab (MK-3475) in Patients With Previously Treated Metastatic Castration-Resistant Prostate Cancer
A Phase 1/2 multicenter, dose determining, open-label study of ADXS31-142 monotherapy and a combination of ADXS31-142 and pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer. Part A will be dose-determining part of ADXS31-142 monotherapy. Part B will be dose-determining part of ADXS31-142 and pembrolizumab (MK-3475) in combination. Part B expansion will treat additional participants with the recommended dose from Part B.
Read the detailed description
Part A of the study will be an open-label, Phase 1, multicenter, non-randomized, dose-determining trial of ADXS31-142 monotherapy in participants with mCRPC. The dose determining phase is intended to select a recommended Phase 2 dose (RP2D) for Part B.
Part B of the study will be an open-label, Phase 1-2, multicenter, non-randomized dose-determining trial of ADXS31-142 in combination with pembrolizumab (MK-3475) in participants with mCRPC. Part B will consist of a dose-determination phase followed by an expansion cohort phase. The dose-determining phase is intended to select an RP2D for the combination.
Dose escalation/de-escalation for this study will be explored by applying the modified toxicity probability interval design.
- Conditions
- Cancer, Prostate Cancer
- Being tested
- ADXS31-142, Pembrolizumab
- Medical subject headings
- Neoplasms, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADXS31-142Drug
ADXS31-142 IV infusion
PembrolizumabDrug
Also called MK-3475
Pembrolizumab IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part A: ADXS31-142 | Experimental | Participants received ADXS31-142 1 × 10^9 colony-forming units (CFU), 5 × 10^9 CFU, or
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. Receives: Drug: ADXS31-142 |
| Part B: ADXS31-142 + Pembrolizumab | Experimental | 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. Receives: Drug: ADXS31-142; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events
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".
Measured: From first dose up to 30 days after last dose (maximum duration: 108 weeks)
Secondary outcomes (4)
Objective Response Rate (ORR)
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.
Measured: From screening until progression or death (maximum duration: 104 weeks)
Objective Response Rate According to Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
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.
Measured: From screening until progression or death (maximum duration: 104 weeks)
Progression-free Survival, Assessed by RECIST Version 1.1
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.
Measured: From screening until progression or death (maximum duration: 104 weeks)
Overall Survival
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.
Measured: From screening until progression or death (maximum duration: 104 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study start4 Jun 2015
- Primary completion30 Aug 2019
- Study completion22 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advaxis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325557
- Sponsor's protocol ID
- ADXS142-03
- Other IDs
- KEYNOTE-046
- Status last verified
- Mar 2024
- First submitted
- 22 Dec 2014
- Last updated
- 2 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stein MN, Fong L, Tutrone R, Mega A, Lam ET, Parsi M, Vangala S, Gutierrez AA, Haas NB. ADXS31142 Immunotherapy +/- Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study. Oncologist. 2022 Jun 8;27(6):453-461. doi: 10.1093/oncolo/oyac048.
PubMed 35373299
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2 Dose-Escalation and Safety Study of ADXS31-142 Alone and of ADXS31-142 in Combination With Pembrolizumab (MK-3475) in Patients With Previously Treated Metastatic Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02325557
- Acronym / sponsor ID
- ADXS142-03
- Conditions
- Cancer, Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Advaxis, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 4 Jun 2015 (actual)
- Primary completion
- 30 Aug 2019 (actual)
- Study completion
- 22 Jan 2020 (actual)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Posted 20 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 1/2 multicenter, dose determining, open-label study of ADXS31-142 monotherapy and a combination of ADXS31-142 and pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer. Part A will be dose-determining part of ADXS31-142 monotherapy. Part B will be dose-determining part of ADXS31-142 and pembrolizumab (MK-3475) in combination. Part B expansion will treat additional participants with the recommended dose from Part B.
Detailed description
Part A of the study will be an open-label, Phase 1, multicenter, non-randomized, dose-determining trial of ADXS31-142 monotherapy in participants with mCRPC. The dose determining phase is intended to select a recommended Phase 2 dose (RP2D) for Part B.
Part B of the study will be an open-label, Phase 1-2, multicenter, non-randomized dose-determining trial of ADXS31-142 in combination with pembrolizumab (MK-3475) in participants with mCRPC. Part B will consist of a dose-determination phase followed by an expansion cohort phase. The dose-determining phase is intended to select an RP2D for the combination.
Dose escalation/de-escalation for this study will be explored by applying the modified toxicity probability interval design.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: ADXS31-142 | Experimental | Drug: ADXS31-142Participants received ADXS31-142 1 × 10^9 colony-forming units (CFU), 5 × 10^9 CFU, or 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 | Experimental | Drug: ADXS31-142, Drug: PembrolizumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have progressive mCRPC, on androgen deprivation therapy, based on at least one of the following criteria:
- Has discontinued antiandrogens (bicalutamide, nilutamide) >6 weeks and enzalutamide >4 weeks prior to Day 1 of trial treatment
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
Key exclusion criteria (7 listed)
- Received more than 3 prior systemic treatment regimens with chemotherapy, hormonal, or immunotherapy in the metastatic setting or received more than 1 prior chemotherapeutic regimen in the metastatic setting
- Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., Grade ≤1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., Grade ≤1 or at baseline) from adverse events due to a previously administered agent.
- Has received prior therapy with an anti-programmed cell death protein-1 (PD-1), anti-programmed death-ligand-1 (PD-L1), or anti-Programmed death-ligand-2 (PD-L2) agent or if the participant has previously participated in a Merck MK-3475 clinical trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADXS31-142ADXS31-142 IV infusion | Drug | Part A: ADXS31-142, Part B: ADXS31-142 + Pembrolizumab |
| PembrolizumabAlso: MK-3475Pembrolizumab IV infusion | Drug | Part B: ADXS31-142 + Pembrolizumab |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events
Time frame: From first dose up to 30 days after last dose (maximum duration: 108 weeks)
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".
4 secondary outcomes
Objective Response Rate (ORR)
Time frame: From screening until progression or death (maximum duration: 104 weeks)
Objective Response Rate According to Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time frame: From screening until progression or death (maximum duration: 104 weeks)
Progression-free Survival, Assessed by RECIST Version 1.1
Time frame: From screening until progression or death (maximum duration: 104 weeks)
Overall Survival
Time frame: From screening until progression or death (maximum duration: 104 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35373299Stein MN, Fong L, Tutrone R, Mega A, Lam ET, Parsi M, Vangala S, Gutierrez AA, Haas NB. ADXS31142 Immunotherapy +/- Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study. Oncologist. 2022 Jun 8;27(6):453-461. doi: 10.1093/oncolo/oyac048.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ADXS31-142 and Pembrolizumab in people with Cancer and Prostate Cancer, run by Advaxis, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (time frame: From first dose up to 30 days after last dose (maximum duration: 108 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02325557, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.