TumorsPhase 1NCT01409135
A Study of the Safety and Pharmacokinetics of AGS-22M6E in Subjects With Malignant Solid Tumors That Express Nectin-4
A Phase 1 study testing AGS-22M6E and ASG-22CE in people with Tumors and Medical Oncology, run by Astellas Pharma Inc at 9 sites in 2 countries.
Trial summary
A study examining the safety of AGS-22M6E or ASG-22CE administered as monotherapy therapy in subjects with malignant solid tumors that express Nectin-4. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumors, Medical Oncology, Neoplasms
- What is being tested?
- AGS-22M6E and ASG-22CE
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 11 Jul 2011to 27 Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- In addition to the inclusion criteria listed above, the following criteria will also be required for each expansion cohort:
- Expansion Cohort 1: Breast Cancer
- Subjects with Histologically or cytologically diagnosed metastatic breast cancer
- Expansion Cohort 2: Bladder Cancer
- Histologically or cytologically confirmed bladder cancer with visceral metastases
- Expansion Cohort 3: Lung plus other solid tumor cancer
- Histologically or cytologically confirmed metastatic non-small cell lung cancer (NSCLC) or any other solid tumor cancer
Who cannot join
- Preexisting neuropathy Grade ≥ 3 or motor neuropathy Grade ≥ 2
- Uncontrolled brain or epidural spinal metastases
- Use of any investigational drug within 14 days or 5 half-lives prior to first dose of study drug
- Any anticancer therapy including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer within 28 days prior to first dose of study drug
- Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
- Known HIV or AIDS
Show all 13Show fewer
- Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
- History of thromboembolic events and bleeding disorders ≤ 3 months (e.g.,deep vein thrombosis ( DVT) or pulmonary embolism ( PE)) prior to first dose of study drug
- Major surgery within 28 days prior to first dose of study drug
- Active infection requiring treatment ≤7 days prior to first dose of study drug
- Anti-androgen therapy initiated within 28 days of enrollment (for prostate cancer patients only)
- Positive Hepatitis B surface antigen test
- Positive Hepatitis C antibody test
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Emory University
Atlanta, Georgia, 30322
University of Colorado, Denver-Aurora
Aurora, Colorado, 80045
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599
Karmanos Cancer institute
Detroit, Michigan, 48201
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS-22M6E or ASG-22CE Given as Monotherapy Followed by Expansion Cohorts in Subjects With Malignant Solid Tumors That Express Nectin-4
A study examining the safety of AGS-22M6E or ASG-22CE administered as monotherapy therapy in subjects with malignant solid tumors that express Nectin-4.
Read the detailed description
AGS-22M6E and ASG-22CE are fully human monoclonal antibody conjugated to a cytotoxic agent monomethyl auristatin E (MMAE) targeting Nectin-4 (Agensys code name AGS-22). The main difference between AGS-22M6E and ASG-22CE is the change in cell line for antibody production. AGS-22M6E and ASG-22CE will be administered at mg/kg doses based on the subjects weight at baseline and doses will not change unless the subjects weight changes by ≥ 10% from their baseline weight or the investigational product Dosage Assessment criteria is met.
Subjects will be prescreened for Nectin-4 expression prior to undergoing screening procedures for the main study. Subjects with tumors positive for Nectin-4 expression may be screened for eligibility into the main study. The dose escalation period is estimated to take between 12 and 18 months depending on whether 3 or 6 subjects are enrolled in a given dose cohort, and the availability of consenting subjects.
Subjects will be treated in the dose escalation phase of the study until the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) has been determined by the data review team (DRT). After the RDE has been determined, subjects will be enrolled into 1 of 3 expansion cohorts. There will be 3 expansion cohorts, each targeting a specific cancer (i.e.,Breast, Bladder and Lung plus other solid tumor cancers). The DRT may recommend stopping the study, adjusting the dose or amending the trial at any time.
The clinical bridging to the ASG-22CE involves treating the subjects with ASG-22CE, irrespective of cancer type, at the next lowest dose level previously determined to be safe for AGS-22M6E. After the initial subjects are treated at the bridging dose with ASG-22CE and have completed the safety assessment, future subjects will only be treated with ASG-22CE throughout the remainder of the study.
A disease assessment will be performed by the investigator at Week 8 (± 14 days). Subjects without evidence of disease progression may continue to receive treatment until disease progression or intolerability.
- Conditions
- Tumors, Medical Oncology, Neoplasms
- Being tested
- AGS-22M6E, ASG-22CE
- Keywords
- Nectin 4 protein, humans, Cancer, Pharmacokinetics of AGS-22M6E, Pharmacokinetics of ASG-22CE, Safety, Clinical Trial, Phase 1, ASG-22ME, AGS-22M6E, ASG-22CE, ASG-22C3
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGS-22M6EDrug
IV Infusion
ASG-22CEDrug
IV Infusion
| Study group | Role | What they receive |
|---|---|---|
| AGS-22M6E-11-1 Dose Level 1 | Experimental | Not described Receives: Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 2 | Experimental | Not described Receives: Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 3 | Experimental | Not described Receives: Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 4 | Experimental | Not described Receives: Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 5 | Experimental | Not described Receives: Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 6 | Experimental | Not described Receives: Drug: AGS-22M6E |
| ASG-22CE Expansion Cohort 1 | Experimental | Breast Cancer Receives: Drug: ASG-22CE |
| ASG-22CE Expansion Cohort 2 | Experimental | Bladder Cancer Receives: Drug: ASG-22CE |
| ASG-22CE Expansion Cohort 3 | Experimental | Lung plus other solid tumor cancers Receives: Drug: ASG-22CE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: Up to 28 days after the last dose of study drug
Composite of Pharmacokinetics: Ceoi or Cmax, Ctrough, Tmax, AUC0-21, t½, CL, Vss
Concentration at the end of infusion (Ceoi) or Cmax, trough concentration (Ctrough), Tmax, partial AUC after first dose (AUC0-21), terminal or apparent terminal half-life (t1/2), systemic clearance (CL), volume of distribution at steady state (Vss)
Measured: Up to 28 days after the last dose of study drug
Secondary outcomes (3)
Incidence of anti-drug antibody formation
Measured: Up to 28 days after the last dose of study drug
Objective tumor response rate
Incidence of a tumor response is defined as a complete or partial response per Response Criteria for Solid Tumors (RECIST version 1.1)
Measured: Every 8 weeks (± 14 days)
Disease Control Rate
Measured: Every 8 weeks (± 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2011 (estimated)
- Study start11 Jul 2011
- Primary completion27 Apr 2015
- Study completion27 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TumorsStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Agensys, Inc., Seagen Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Agensys, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01409135
- Sponsor's protocol ID
- AGS-22M6E-11-1
- Status last verified
- Feb 2024
- First submitted
- 29 Jul 2011
- Last updated
- 12 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS-22M6E or ASG-22CE Given as Monotherapy Followed by Expansion Cohorts in Subjects With Malignant Solid Tumors That Express Nectin-4
- ClinicalTrials.gov ID
- NCT01409135
- Acronym / sponsor ID
- AGS-22M6E-11-1
- Conditions
- Tumors, Medical Oncology, Neoplasms
- Keywords
- Nectin 4 protein, humans, Cancer, Pharmacokinetics of AGS-22M6E, Pharmacokinetics of ASG-22CE, Safety, Clinical Trial, Phase 1, ASG-22ME, AGS-22M6E
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Astellas Pharma IncIndustry (pharma, biotech, devices)
- Collaborators
- Agensys, Inc., Seagen Inc.
- Study start
- 11 Jul 2011 (actual)
- Primary completion
- 27 Apr 2015 (actual)
- Study completion
- 27 Apr 2015 (actual)
- First posted
- 4 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study examining the safety of AGS-22M6E or ASG-22CE administered as monotherapy therapy in subjects with malignant solid tumors that express Nectin-4.
Detailed description
AGS-22M6E and ASG-22CE are fully human monoclonal antibody conjugated to a cytotoxic agent monomethyl auristatin E (MMAE) targeting Nectin-4 (Agensys code name AGS-22). The main difference between AGS-22M6E and ASG-22CE is the change in cell line for antibody production. AGS-22M6E and ASG-22CE will be administered at mg/kg doses based on the subjects weight at baseline and doses will not change unless the subjects weight changes by ≥ 10% from their baseline weight or the investigational product Dosage Assessment criteria is met.
Subjects will be prescreened for Nectin-4 expression prior to undergoing screening procedures for the main study. Subjects with tumors positive for Nectin-4 expression may be screened for eligibility into the main study. The dose escalation period is estimated to take between 12 and 18 months depending on whether 3 or 6 subjects are enrolled in a given dose cohort, and the availability of consenting subjects.
Subjects will be treated in the dose escalation phase of the study until the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) has been determined by the data review team (DRT). After the RDE has been determined, subjects will be enrolled into 1 of 3 expansion cohorts. There will be 3 expansion cohorts, each targeting a specific cancer (i.e.,Breast, Bladder and Lung plus other solid tumor cancers). The DRT may recommend stopping the study, adjusting the dose or amending the trial at any time.
The clinical bridging to the ASG-22CE involves treating the subjects with ASG-22CE, irrespective of cancer type, at the next lowest dose level previously determined to be safe for AGS-22M6E. After the initial subjects are treated at the bridging dose with ASG-22CE and have completed the safety assessment, future subjects will only be treated with ASG-22CE throughout the remainder of the study.
A disease assessment will be performed by the investigator at Week 8 (± 14 days). Subjects without evidence of disease progression may continue to receive treatment until disease progression or intolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| AGS-22M6E-11-1 Dose Level 1 | Experimental | Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 2 | Experimental | Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 3 | Experimental | Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 4 | Experimental | Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 5 | Experimental | Drug: AGS-22M6E |
| AGS-22M6E-11-1 Dose Level 6 | Experimental | Drug: AGS-22M6E |
| ASG-22CE Expansion Cohort 1 | Experimental | Drug: ASG-22CEBreast Cancer |
| ASG-22CE Expansion Cohort 2 | Experimental | Drug: ASG-22CEBladder Cancer |
| ASG-22CE Expansion Cohort 3 | Experimental | Drug: ASG-22CELung plus other solid tumor cancers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- In addition to the inclusion criteria listed above, the following criteria will also be required for each expansion cohort:
- Expansion Cohort 1: Breast Cancer
- Subjects with Histologically or cytologically diagnosed metastatic breast cancer
- Expansion Cohort 2: Bladder Cancer
- Histologically or cytologically confirmed bladder cancer with visceral metastases
Key exclusion criteria (13 listed)
- Preexisting neuropathy Grade ≥ 3 or motor neuropathy Grade ≥ 2
- Uncontrolled brain or epidural spinal metastases
- Use of any investigational drug within 14 days or 5 half-lives prior to first dose of study drug
- Any anticancer therapy including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer within 28 days prior to first dose of study drug
- Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
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 |
|---|---|---|
| AGS-22M6EIV Infusion | Drug | AGS-22M6E-11-1 Dose Level 1, AGS-22M6E-11-1 Dose Level 2, AGS-22M6E-11-1 Dose Level 3, AGS-22M6E-11-1 Dose Level 4, AGS-22M6E-11-1 Dose Level 5, AGS-22M6E-11-1 Dose Level 6 |
| ASG-22CEIV Infusion | Drug | ASG-22CE Expansion Cohort 1, ASG-22CE Expansion Cohort 2, ASG-22CE Expansion Cohort 3 |
Primary outcome
Incidence of adverse events
Time frame: Up to 28 days after the last dose of study drug
Composite of Pharmacokinetics: Ceoi or Cmax, Ctrough, Tmax, AUC0-21, t½, CL, Vss
Time frame: Up to 28 days after the last dose of study drug
Concentration at the end of infusion (Ceoi) or Cmax, trough concentration (Ctrough), Tmax, partial AUC after first dose (AUC0-21), terminal or apparent terminal half-life (t1/2), systemic clearance (CL), volume of distribution at steady state (Vss)
3 secondary outcomes
Incidence of anti-drug antibody formation
Time frame: Up to 28 days after the last dose of study drug
Objective tumor response rate
Time frame: Every 8 weeks (± 14 days)
Disease Control Rate
Time frame: Every 8 weeks (± 14 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Link to results and other applicable study documents on the Astellas Clinical Trials websiteLink provided by the sponsor.
- Link to plain language summary of the study on the Trial Results Summaries websiteLink provided by the sponsor.
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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.
Medical Monitor study director
Agensys, Inc.
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AGS-22M6E and ASG-22CE in people with Tumors and Medical Oncology, run by Astellas Pharma Inc at 9 sites in 2 countries.
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 7 inclusion and 13 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 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of adverse events (time frame: Up to 28 days after the last dose of study drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Mar 2024.