Description:
This is a Phase I, open-label, dose-escalation, single arm study to explore the safety,
tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT
cell therapy, in subjects with relapsed/refractory MM, as well as define the RP2D.
Title
- Brief Title: AGENT-797 in Patients With Relapsed/Refractory Multiple Myeloma
- Official Title: A Phase I Open-Label Study of the Safety, Tolerability and Preliminary Clinical Activity of Allogeneic Invariant Natural Killer (iNKT) Non-transduced Cells (agenT-797) in Patients With Relapsed/Refractory Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
2019-1305
- NCT ID:
NCT04754100
Conditions
- Relapsed/Refractory Multiple Myeloma
Interventions
Drug | Synonyms | Arms |
---|
agenT-797 | | Dosage and Cohorts |
Purpose
This is a Phase I, open-label, dose-escalation, single arm study to explore the safety,
tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT
cell therapy, in subjects with relapsed/refractory MM, as well as define the RP2D.
Detailed Description
This is a Phase I, open-label, dose-escalation, single arm study to explore the safety,
tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT
cell therapy, in subjects with relapsed/refractory MM, as well as define the RP2D.
In Part 1, the study will employ a standard 3+3 dose escalation design, for which 3 to 6
evaluable subjects (maximally 9 if recommended by the Safety Review Committee [SRC]) will be
enrolled at each assigned dose level, per cohort depending on the occurrence of DLTs.
Part 2 will consist of one or more cohorts of in total up to around 6 to 12 subjects with
relapsed/refractory MM who receive agenT-797 at a given dose after lymphodepletion and will
employ a 3+3 dose escalation/de-escalation design depending on the occurrence of DLTs. The
starting dose in Part 2 will be equal to the maximum tolerated dose (MTD) defined in Part 1
in the absence of any DLTs at that dose level. If a DLT is observed at the MTD in Part 1, the
starting dose level in Part 2 will be the dose level below MTD.
Details of the analyses will be described in a statistical analysis plan.
A Safety Monitoring Committee will be established to assess safety and decide on escalation
to next Cohort.
Trial Arms
Name | Type | Description | Interventions |
---|
Dosage and Cohorts | Experimental | Part 1: Dose escalation without lymphodepletion.
Dosage Frequency and Mode of Administration: agenT-797 will be administered to subjects as a single IV infusion.
Part 2: Dose escalation with lymphodepletion (optional)
Dosage Frequency and Mode of Administration: Subjects will receive lymphodepletion before infusion of agenT-797. Starting dose will be defined based on data from Part 1. | |
Eligibility Criteria
Inclusion Criteria:
- Written informed consent obtained prior to any screening procedures and in accordance
with federal, local, and institutional guidelines.
- Age ≥ 18 years.
- Confirmed diagnosis, and evidence of progressive disease or clinical relapse as
defined by International Myeloma Working Group (IMWG) criteria and following prior
therapy for MM:
1. Relapsed or refractory MM requiring current treatment.
2. Previously failed ≥ 3 prior regimens.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.
- Estimated life expectancy ≥ 4 months.
- No other medical, surgical, or psychiatric condition (including active substance
abuse) that would interfere with compliance to the protocol, as determined by the
Principal Investigator.
- Female subjects of childbearing potential must agree to use dual methods of
contraception and have a negative serum pregnancy test at Screening, and male subjects
must use an effective barrier method of contraception if sexually active with a female
of childbearing potential.
- Subjects need a functioning, central venous access in place for the administration of
agenT-797.
Exclusion Criteria:
- Pregnant or nursing women.
- Prior history of invasive malignancy.
- Subjects who had an allogeneic stem cell transplantation and are still on
immunosuppressive medications or corticosteroids above physiological dose.
- New York Heart Association Class III or IV heart failure, unstable angina, or a
history of recent myocardial infarction.
- Adverse events from prior anticancer therapy that have not resolved to NCI CTCAE Grade
≤ 1.
- Receiving any investigational products within 4 weeks or 5 half-lives of cell
infusion.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of AEs |
Time Frame: | Up to day 28 post cell infusion. |
Safety Issue: | |
Description: | Number of participants with treatment-related AEs as determined per NIC CTCAE v5.0 |
Secondary Outcome Measures
Measure: | Persistence of allogeneic iNKT cells. |
Time Frame: | Baseline, 2 hours post cell infusion, and on Days 2, 3, 5, 8, 15, 22, and 29, Weeks 6, 8, and 12, and Months 6, 9, and 12. |
Safety Issue: | |
Description: | Persistence of agenT-797 in peripheral blood (SNP-based assay) |
Measure: | Clinical response evaluation. |
Time Frame: | End of study visit (up to 12 months). |
Safety Issue: | |
Description: | Evaluation using the International Myeloma Working Group (IMWG) consensus criteria. |
Measure: | Evaluation of immune response to donor cells |
Time Frame: | Baseline, Day 22, Week 6 and end of study visit (up to 12 months). |
Safety Issue: | |
Description: | Measurement of serum alloantibodies to MHC Class I and II |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AgenTus Therapeutics, Inc. |
Trial Keywords
Last Updated
May 6, 2021