Safety and Efficacy of ALLO-715 and ALLO-647 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)

Overview

About this study

The purpose of this research study is to find out if the experimental treatment, ALLO-715 in combination with ALLO-647, is safe and effective in treating multiple myeloma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Documented diagnosis of relapsed/refractory multiple myeloma (MM) with measurable
disease (serum, urine, or free light chain [FLC]) per International Myeloma Working
Group (IMWG) criteria

- At least 3 prior lines of MM therapy, including a proteasome inhibitor,
immunomodulatory agent, and anti-CD38 antibody (unless contraindicated), and
refractory to the last treatment line.

- Eastern Cooperative Oncology Group (ECOG) 0 or 1

- Absence of donor (product)-specific anti-HLA antibodies

- Adequate hematologic, renal, hepatic, pulmonary, and cardiac function

Exclusion Criteria:

- Current or history of Central Nervous System (CNS) involvement of myeloma or plasma
cell leukemia

- Clinically significant CNS disorder

- Current or history of thyroid disorder

- Autologous stem cell transplant within the last 6 weeks, or any allogeneic stem cell
transplant

- Prior treatment with anti-BCMA therapy, any gene therapy, any genetically modified
cell therapy, or adoptive T cell therapy

- History of HIV infection or acute or chronic active hepatitis B or C infection

- Patients unwilling to participate in an extended safety monitoring period

Additional Exclusion Criteria for Nirogacestat plus ALLO-715 Cohorts

- Inability to swallow tablets

- Subject has known malabsorption syndrome or preexisting gastrointestinal conditions
that may impair absorption of nirogacestat

- Use of strong/moderate CYP3A4 inhibitors, and strong CYP3A4 inducers within 14 days
before starting nirogacestat.

- Use of concomitant medications that are known to prolong the QT/QTcF interval

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 3/8/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Rochester, Minn. Mayo Clinic principal investigator Shaji Kumar, M.D.	Closed for enrollment	Contact information: Cancer Center Clinical Trials Referral Office 855-776-0015

Mayo Clinic Location

Status

Contact

Rochester, Minn.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen. Key secondary endpoints were response rate and duration of response. Grade ≥3 adverse events were reported in 38 (88.0%) of patients. Cytokine release syndrome was observed in 24 patients (55.8%), with 1 grade ≥3 event (2.3%) and neurotoxicity in 6 patients (14%), with no grade ≥3 events. Infections occurred in 23 patients (53.5%), with 10 (23.3%) of grade ≥3. Overall, 24 patients (55.8%) had a response. Among patients treated with 320 × 10 CAR T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n = 24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma. Read More on PubMed

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