Antigen-specific T Cell Therapy for Patients With Relapsed Refractory Multiple Myeloma

NCT04505813 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: NEXI-002-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

This Research study is being done to characterize the safety, tolerability, and preliminary antitumor activity of the NEXI-002 T cell product (a new experimental therapy), which contains populations of CD8+ T cells targeting multiple Myeloma associated antigen peptides in patients with relapsed refractory multiple myeloma (MM). The study will enroll patients with MM who have relapsed or are refractory to standard lines of treatment. The enrolled patients will undergo bridging therapy for the purposes of disease control while the NEXI-002 T cell product is being manufactured. Choice of bridging therapy administered will be per the Investigator's discretion, but is limited to acceptable agents as specified in the protocol. Bridging therapy will be administered prior to lymphodepleting (LD) therapy, with the last dose of the bridging therapy administered ≥ 14 days prior to initiation of LD therapy. Within 72 hours after completing LD therapy, patients will receive a single IV infusion of the NEXI-002 T cell product.

Conditions

Relapsed Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (9)

• Adverse Events of Special Interest (AESIs) events

  1\) Dose Limiting Toxicities (DLTs).

  1 year

• Progressive Free Survival

  Median Progressive free Survival (PFS)

  At 12 months

• Overall Response Survival (Rate)

  Overall Response Rate (ORR)

  At 12 months

• Survival

  Overall Survival (OS)

  At 12 months

• Adverse events (AEs) Reporting

  Incidence of TEAEs leading to study withdrawal

  At year 1

• Adverse Events of Special Interest (AESIs) events (AEs) Reporting

  Cytokine Release Syndrome (CRS)

  at year 1

• Adverse Events of Special Interest (AESIs)events (AEs) Reporting (ICANS)

  Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)

  at year 1

• Adverse Events of Special Interest (AESIs)events (AEs) Reporting-TEAEs

  For Incidence of TEAEs and serious TEAEs (Treatment-emergent adverse events (TEAEs) are defined as those AEs that started on or after LD therapy or that worsened after LD therapy.

  At year 1

• Adverse Events of Special Interest (AESIs)events (AEs) Reporting-Infusion Reactions

  Infusion Related Reactions (IRR)

  At year 1

Study Arms (2)

Safety Evaluation Phase

EXPERIMENTAL

Treatment with NEXI-002 T cells, derived from PBMCs of the patient

Biological: NEXI-002 T Cells

Dose Expansion Phase

EXPERIMENTAL

Dose Expansion Phase to further define the safety, tolerability and initial anti-tumor efficacy of the NEXI- 002 T cell product at the dose established from the Safety Evaluation Phase.

Biological: NEXI-002 T Cells

Interventions

NEXI-002 T Cells BIOLOGICAL

The NEXI-001 T cell product will be administered as a single IV infusion to patients within 72 hours after completing LD therapy.

Dose Expansion Phase; Safety Evaluation Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease. Patients must also be willing and able to comply with study procedures, including the acquisition of specified research specimens
• Age ≥ 18 years old \& life expectancy \> 3 months
• Expression of HLA-A\*0201 as determined by high resolution sequence-based typing method
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with exception of ECOG \> 1 if related to recent bone fracture
• Patients must have confirmed diagnosis of MM
• Have identified relapsed/refractory disease which includes:
• Previous therapy consisting of at least three (3) standard regimens, including a proteasome inhibitor, IMiD, or anti-CD38 targeting therapy.
• Note: Induction therapy, autologous stem cell transplantation (ASCT) \& maintenance therapy if given sequentially without intervening progressive disease (PD) are considered one 'regimen'
• Refractory MM may be defined as disease that is refractory to treatment while on therapy or that shows progression within 60 days of the last therapy.
• Have measurable disease as defined by:
• Serum M protein ≥ 0.5 g/dL
• Urine M protein ≥ 200 mg/24hr
• Serum free light chains (FLC) ≥ 10 mg/dL with abnormal FLC ratio Note: Patients with IgA MM in whom serum protein electrophoresis (sPEP) is deemed unreliable, due to co-migration of normal serum proteins with the paraprotein in the β region, may be considered eligible as long as total serum IgA level is \> normal range.
• Acceptable laboratory parameters as follows:
• AST/ALT ≤ 2.5 × ULN

You may not qualify if:

• Have active cerebral or meningeal disease related to the underlying malignancy
• Have hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, amyloidosis, plasmacytoma, significant autoimmune or other malignant disease
• History of allogeneic hematopoietic stem cell transplantation
• Have active or uncontrolled infections with positive cultures and/or requiring treatment with IV anti-infective agents
• Echocardiogram or MUGA with left ventricular ejection fraction \< 45%
• History of clinically significant cardiovascular disease including but not limited to:
• Myocardial infarction or unstable angina within the 6 months prior to the initiation of study
• Stroke or transient ischemic attack within 6 months prior to initiation of study
• Clinically significant cardiac arrhythmia
• Uncontrolled hypertension: systolic blood pressure (SBP) \> 180 mmHg, diastolic blood pressure (DBP) \> 100 mmHg
• Congestive heart failure (New York Heart Association \[NYHA\] class III-IV)
• Pericarditis or clinically significant pericardial effusion
• Myocarditis
• Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation
• Eligible patients will not be on any steroids ≥10 mg per day prednisone or equivalent or other immunosuppressants such as tacrolimus, cyclosporine, etc.

Sponsors & Collaborators

• NexImmune Inc.: lead

Study Sites (6)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Advent Health Medical Group Blood & Marrow Transplant

Orlando, Florida, 32804, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Kristi Jones

  NexImmune

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 10, 2020
• Study Start: August 17, 2020
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2025
• Last Updated: January 16, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)