Malignant Pleural MesotheliomaPhase 2NCT03175172

Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)

A Phase 2 study testing CRS-207 and Pembrolizumab in people with Malignant Pleural Mesothelioma, run by Aduro Biotech, Inc. at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

The purpose of this study is to evaluate whether CRS-207 with pembrolizumab is safe and effective in adults with MPM who have failed prior anti-cancer therapy. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Malignant Pleural Mesothelioma
What is being tested?: CRS-207 and Pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 8 sitesUnited States
Study dates: 31 May 2017to 31 Jan 2018
Phase: Phase 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
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (≥50%) epithelial component
No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Adequate organ and marrow function
Adequate lung function; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air

Who cannot join

Pleurodesis within 14 days prior to first dose of study drug
Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Active secondary malignancy
Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or not recovered from adverse effects due to agents administered more than 4 weeks earlier
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug
History of (non-infectious) pneumonitis that required steroids or current pneumonitis

Show all 9Show fewer

Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)
Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy
Implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g., artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)) if infection occurs. Other common devices such as venous access devices (e.g., Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and breast implants that were placed more than 3 months prior to first dose of study drug.

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

NIH National Cancer Institute
Bethesda, Maryland, 20892
University of Chicago Medical Center
Chicago, Illinois, 60637
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Laura & Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
UCSF Comprehensive Cancer Center
San Francisco, California, 94115
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma

The purpose of this study is to evaluate whether CRS-207 with pembrolizumab is safe and effective in adults with MPM who have failed prior anti-cancer therapy.

Read the detailed description

The population for this study will consist of approximately 35 adults with histologically-confirmed MPM (epithelial or biphasic) whose disease has progressed after 1-2 prior anti-cancer therapies.

Conditions: Malignant Pleural Mesothelioma
Being tested: CRS-207, Pembrolizumab
Medical subject headings: Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CRS-207Biological
Administered by IV infusion over approximately 1 hour.
PembrolizumabBiological
Also called MK-3475
Administered by IV infusion over approximately 30 minutes.

Study groups in NCT03175172
Study group	Role	What they receive
Experimental	Experimental	CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit. Receives: Biological: CRS-207; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Response Rate (ORR)
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (modified RECIST) for MPM (Byrne and Nowak, 2004) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure.
Measured: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.

Secondary outcomes (4)

Disease Control Rate (DCR)
The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.
Measured: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Progression-Free Survival (PFS)
Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) (per modified RECIST for MPM) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CI). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last tumor assessment or data cut-off date, whichever is earlier.
Measured: Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 9 weeks.
Improvement in Pulmonary Function
Percentage of subjects with improvement in forced vital capacity (FVC), defined as an increase from baseline of either ≥400 mL or ≥20% assessed using spirometry
Measured: Subjects tested by spirometry at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 until 4 weeks post final dose, assessed up to 16 weeks.
Overall Survival (OS)
Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier.
Measured: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 May 201731 Jan 2018

First posted5 Jun 2017
Study start31 May 2017
Primary completion9 Jan 2018
Study completion31 Jan 2018

Why it stopped: Study was stopped due to low enrollment and lack of clinical activity.

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 Malignant Pleural MesotheliomaStudies 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03175172
Sponsor's protocol ID: ADU-CL-13
Other IDs: KEYNOTE KN-701
Status last verified: Mar 2019
First submitted: 1 Jun 2017
Last updated: 4 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004 Feb;15(2):257-60. doi: 10.1093/annonc/mdh059.
PubMed 14760119

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Efficacy and Safety of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma, Advanced
RecruitingPhase 2
The Diagnostic Accuracy and Clinical Value of FAPI PET in Pleural Mesothelioma
Pleural Mesothelioma, Pleural Diseases
Active, not recruitingPhase 1
Safety and Preliminary Antitumor Activity of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma, Advanced
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
SW-682 in Advanced Solid Tumors
Advanced Solid Tumor, Mesothelioma, Malignant

All Malignant Pleural Mesothelioma trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma
ClinicalTrials.gov ID: NCT03175172
Acronym / sponsor ID: ADU-CL-13
Conditions: Malignant Pleural Mesothelioma
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study was stopped due to low enrollment and lack of clinical activity.
Enrolment: 10 participants (actual)
Lead sponsor: Aduro Biotech, Inc.Industry (pharma, biotech, devices)
Collaborators: Merck Sharp & Dohme LLC
Study start: 31 May 2017 (actual)
Primary completion: 9 Jan 2018 (actual)
Study completion: 31 Jan 2018 (actual)
First posted: 5 Jun 2017 (actual)
Results: Posted 19 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate whether CRS-207 with pembrolizumab is safe and effective in adults with MPM who have failed prior anti-cancer therapy.

Detailed description

The population for this study will consist of approximately 35 adults with histologically-confirmed MPM (epithelial or biphasic) whose disease has progressed after 1-2 prior anti-cancer therapies.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental	Experimental	Biological: CRS-207, Biological: PembrolizumabCRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (≥50%) epithelial component
No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Adequate organ and marrow function
Adequate lung function; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air

Key exclusion criteria (9 listed)

Pleurodesis within 14 days prior to first dose of study drug
Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Active secondary malignancy
Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or not recovered from adverse effects due to agents administered more than 4 weeks earlier
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug

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
CRS-207Administered by IV infusion over approximately 1 hour.	Biological	Experimental
PembrolizumabAlso: MK-3475Administered by IV infusion over approximately 30 minutes.	Biological	Experimental

Primary outcome

Overall Response Rate (ORR)
Time frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (modified RECIST) for MPM (Byrne and Nowak, 2004) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure.

4 secondary outcomes

Disease Control Rate (DCR)
Time frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Progression-Free Survival (PFS)
Time frame: Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 9 weeks.
Improvement in Pulmonary Function
Time frame: Subjects tested by spirometry at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 until 4 weeks post final dose, assessed up to 16 weeks.
Overall Survival (OS)
Time frame: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.

Results and safety

Results posted to the registry on 19 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Experimental	10	0

Primary outcome: Overall Response Rate (ORR)

Time frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.. Count of participants. Unit: Participants

Measure	Experimental n = 9
Complete Response	0
Partial Response	0
Stable Disease	1
Progressive Disease	8
Not Evaluable	0

Population analysed: Analysis based on subjects who received ≥1 dose of study treatment and had ≥1 evaluable post-baseline modified RECIST for MPM tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set \[EAS\]). 1 subject did not have post-baseline tumor response assessments and could not be evaluated for this outcome measure.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Subjects were followed for serious and non-serious adverse events (AEs) from the beginning of any study drug until 28 days following the last dose of study drug or initiation of a subsequent cancer-related therapy, whichever is earlier, an average of 3 months. Subjects were followed for survival for 12 months after end-of-treatment (EOT) or until study termination on 31 January 2018, whichever is earlier, an average of 14 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Experimental	4 of 10 (40%)	10 of 10 (100%)	3 of 10

Limitations and caveats (from the sponsor): Study was terminated early and included a small number of subjects, and insufficient data were available to evaluate the clinical activity of the study treatment. Due to low enrollment, some protocol-specified outcome measures were not evaluated.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 14760119Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004 Feb;15(2):257-60. doi: 10.1093/annonc/mdh059.
Individual participant dataSharing planned: No

Related trials for Malignant Pleural Mesothelioma

RecruitingPhase 1/2
Efficacy and Safety of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma, Advanced
RecruitingPhase 2
The Diagnostic Accuracy and Clinical Value of FAPI PET in Pleural Mesothelioma
Pleural Mesothelioma, Pleural Diseases
Active, not recruitingPhase 1
Safety and Preliminary Antitumor Activity of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma, Advanced
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
SW-682 in Advanced Solid Tumors
Advanced Solid Tumor, Mesothelioma, Malignant

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 2 study testing CRS-207 and Pembrolizumab in people with Malignant Pleural Mesothelioma, run by Aduro Biotech, 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 5 inclusion and 9 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: stopped early, as of the sponsor's last update on 4 Apr 2019. 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 phase mean?

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 19 Feb 2019). 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?

Overall Response Rate (ORR) (time frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 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 NCT03175172, 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 4 Apr 2019.