Gastric AdenocarcinomaPhase 2NCT03122548

Safety and Efficacy of CRS-207 With Pembrolizumab in Gastric, Gastroesophageal Junction or Esophageal Cancers

A Phase 2 study testing CRS-207 and Pembrolizumab in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, 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

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Trial summary

The purpose of this study is to determine whether CRS-207 in combination with pembrolizumab is safe and effective in adults with recurrent or metastatic gastric, gastroesophageal junction, or esophageal cancer who have received one or two prior chemotherapy regimens for advanced disease. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
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: 5 participants
Where: 8 sitesUnited States
Study dates: 14 Aug 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

Diagnosis with confirmed histology of one or more of the following:
Histologically-confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma (Siewert type II/III classification), or
Histologically-confirmed inoperable superior, medial, or distal third esophageal adenocarcinoma (Siewert type I classification may be included, provided there is no mixed histology)
Confirmed recurrent or metastatic disease
Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease.
HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab; prior treatment must have included a platinum and a fluoropyrimidine.

Show all 9Show fewer

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Can provide tissue for PD-L1 and mesothelin biomarker analysis
Adequate organ and marrow function at screening

Who cannot join

Diagnosis of squamous or undifferentiated gastric cancer
Individuals with inaccessible tumors or for whom biopsy is contraindicated
Participated in any other study in which receipt of an investigational new drug or investigational device occurred within 28 days of 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
Clinical evidence of ascites by physical exam
Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug or has 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, or has not recovered from adverse effects due to a previously-administered agent
Subjects who have 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

University of Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287
University of Chicago Medical Center
Chicago, Illinois, 60637
Mary Crowley Cancer Research
Dallas, Texas, 75230
Henry Ford Hospital
Detroit, Michigan, 48202
UCLA Medical Center
Los Angeles, California, 90095
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Virginia Mason Medical Center
Seattle, Washington, 98101

Other trials in United States

About this study

Official title: A Phase 2, Open-label Evaluation of CRS-207 and Pembrolizumab in Adults With Recurrent or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinomas

Conditions: Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
Being tested: CRS-207, Pembrolizumab
Keywords: stomach cancer, gastric cancer, esophageal cancer, digestive system diseases, gastrointestinal diseases, stomach diseases
Medical subject headings: Adenocarcinoma Of Esophagus, Stomach Neoplasms, Esophageal Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Stomach Diseases

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

Study groups in NCT03122548
Study group	Role	What they receive
CRS-207 + Pembrolizumab	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.

Objective 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 evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) 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 post-baseline tumor assessment until documented disease progression, starting of a 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 RECIST v1.1.
Measured: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a 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) according to RECIST v1.1 or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). 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 evaluable 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 15 weeks.
Duration of Response (DOR)
Number of weeks from the first date a study subject achieved an objective disease response of CR or PR according to RECIST v1.1 to the date a study subject exhibited PD or death due to any cause, estimated using KM methods with 95% CIs. Subjects who do not experience PD or death at the time of analysis will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Measured: DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 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 15 weeks.

Timeline

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

14 Aug 201731 Jan 2018

First posted21 Apr 2017
Study start14 Aug 2017
Primary completion27 Dec 2017
Study completion31 Jan 2018

Why it stopped: Low enrollment and lack of clinical activity in other CRS-207 studies.

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.
Other trials for Gastric AdenocarcinomaStudies 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: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03122548
Sponsor's protocol ID: ADU-CL-14
Other IDs: KEYNOTE KN-463
Status last verified: Mar 2019
First submitted: 4 Apr 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

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

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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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Oesophageal Cancer, Gastric Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingPhase 2
Perioperative Chemotherapy With Low-Dose Radiotherapy and Tislelizumab for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
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RecruitingPhase 2
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All Gastric Adenocarcinoma 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, Open-label Evaluation of CRS-207 and Pembrolizumab in Adults With Recurrent or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinomas
ClinicalTrials.gov ID: NCT03122548
Acronym / sponsor ID: ADU-CL-14
Conditions: Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
Keywords: stomach cancer, gastric cancer, esophageal cancer, digestive system diseases, gastrointestinal diseases, stomach diseases
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Low enrollment and lack of clinical activity in other CRS-207 studies.
Enrolment: 5 participants (actual)
Lead sponsor: Aduro Biotech, Inc.Industry (pharma, biotech, devices)
Collaborators: Merck Sharp & Dohme LLC
Study start: 14 Aug 2017 (actual)
Primary completion: 27 Dec 2017 (actual)
Study completion: 31 Jan 2018 (actual)
First posted: 21 Apr 2017 (actual)
Results: Posted 20 Feb 2019

Clinical summary

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

Study design

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

Arm	Type	Receives
CRS-207 + Pembrolizumab	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 (9 listed)

Diagnosis with confirmed histology of one or more of the following:
Confirmed recurrent or metastatic disease
Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease.
HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab; prior treatment must have included a platinum and a fluoropyrimidine.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Key exclusion criteria (8 listed)

Diagnosis of squamous or undifferentiated gastric cancer
Individuals with inaccessible tumors or for whom biopsy is contraindicated
Participated in any other study in which receipt of an investigational new drug or investigational device occurred within 28 days of 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
Clinical evidence of ascites by physical exam

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

Primary outcome

Objective Response Rate (ORR)
Time frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a 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 evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) 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 post-baseline tumor assessment until documented disease progression, starting of a 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 15 weeks.
Duration of Response (DOR)
Time frame: DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 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 15 weeks.

Results and safety

Results posted to the registry on 20 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
CRS-207 + Pembrolizumab	5	0

Primary outcome: Objective Response Rate (ORR)

Time frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.. Count of participants. Unit: Participants

Measure	CRS-207 + Pembrolizumab n = 3
Complete Response	0
Partial Response	0
Stable Disease	0
Progressive Disease	3
Not Evaluable	0

Population analysed: Analysis based upon subjects who received at least 1 dose of CRS-207 and had at least 1 evaluable post-baseline RECIST v1.1 tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set \[EAS\]). 2 subjects 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 treatment until 28 days following the last dose of study drug or until the subject initiates a new cancer therapy, whichever is earlier, an average of 3 months. Subjects were followed for survival for at least 12 months after end-of-treatment (EOT), or until death, loss to follow-up, or study termination, whichever is earlier, an average of 10 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CRS-207 + Pembrolizumab	4 of 5 (80%)	5 of 5 (100%)	3 of 5

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.
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 2 study testing CRS-207 and Pembrolizumab in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, 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 9 inclusion and 8 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 20 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?

Objective Response Rate (ORR) (time frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a 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 NCT03122548.

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.