NCT07045909

Efficacy and Safety of Anitocabtagene Autoleucel in Participants With Newly Diagnosed Multiple Myeloma (GEM-AnitoFIRST)

A Phase 2, Open-label, Multicenter Multi-cohort Study to Evaluate the Efficacy and Safety of Anitocabtagene Autoleucel in Participants With Newly Diagnosed Multiple Myeloma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: PETHEMA Foundation · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if anitocabtagene autoleucel following induction therapy works to treat adult participants with newly diagnosed multiple myeloma. The main objectives of this clinical trial are: * To determine the incidence and severity of all adverse events (AEs). * To determine the proportion of patients achieving undetectable minimal residual disease (uMRD) negative-CR rate (minimum 10 to -5) at 12 months (+/- 3 months) after enrollment. Participants will receive induction therapy with a quadruplet regimen including a proteasome inhibitor (Bortezomib \[V\]), immunomodulatory drug (Lenalidomide \[R\]), dexamethasone \[d\] and anti-CD38 monoclonal antibody (Daratumumab \[D\] or Isatuximab \[Isa\]) followed by anitocabtagene autoleucel. Participants in Cohorts A and B will receive lenalidomide maintenance therapy following infusion with anitocabtagene autoleucel.

Detailed description

Approximately 30 participants will be enrolled to receive induction therapy followed by a single dose of anitocabtagene autoleucel (\~ 10 patients treated at target treatment dose per cohort). Participants will be distributed in 3 cohorts of treatment (A, B and C). Participants of cohort A will be transplant eligible while participants of cohorts B and C will not be planned to receive transplantation: 1. Induction therapy: * Cohort A: will consist of a total of 6 cycles D-VRd (28-day cycles); 3 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 3 additional cycles. * Cohort B: will consist of a total of 4 cycles Isa-VRd (42-day cycles); 2 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 2 additional cycles. * Cohort C: will consist of a total of 4 cycles Isa-VRd (42-day cycles); 2 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 2 additional cycles. 2. Bridging Therapy: Bridging therapy will not be required because the leukapheresis and manufacturing will be planned during the induction phase to allow the availability of anitocabtagene autoleucel at the end of the induction therapy. 3. Lymphodepleting Chemotherapy: Chemotherapy regimen consisting of cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day will be administered intravenously (IV) daily for 3 days (Days -5 through -3) before administration of anitocabtagene autoleucel. The fludarabine dose may be adjusted for renal function. Initiation of the 3-day lymphodepleting chemotherapy regimen on Day -7 or Day -6 prior to the anitocabtagene autoleucel infusion on Day +1 is permitted. 4. Anitocabtagene Autoleucel: Treatment consists of a single infusion of anitocabtagene autoleucel administered intravenous (IV) on Day 1 at a target dose of 115 x 10e6 (± 10 x 10e6) CAR+ viable T cells. 5. Maintenance Therapy: Cohorts A and B will receive maintenance therapy which will consist of lenalidomide 10 mg daily (days 1 to 28 of repeated 28-day cycle) for 2 years or until unacceptable toxicity, progression as per IMWG criteria, participant withdrawal of consent, death, or study completion, whichever occurs first. If any of these circumstances occur participant maintenance will end. After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated.

Conditions

• De Novo Multiple Myeloma
• Anitocabtagene Autoleucel

Interventions

Type	Name	Description
DRUG	Daratumumab	Daratumumab will be administered by subcutaneous (SC) injection.
DRUG	Isatuximab	Isatuximab will be administered IV.
DRUG	Bortezomib	Bortezomib dose will be calculated using the patient's actual body surface area at baseline and will be administered by SC injection.
DRUG	Lenalidomide	Lenalidomide will be administered by oral route (all cohorts at induction, and cohorts A and B at maintenance).
DRUG	Cyclophosphamide	As part of lymphodepleting therapy before CAR-T manufacture, administered IV.
DRUG	Fludarabine	As part of lymphodepleting therapy before CAR-T manufacture, administered IV
DRUG	Anitocabtagene Autoleucel	Single infusion IV

Timeline

• Start date: 2025-06-30
• Primary completion: 2028-03-31
• Completion: 2030-03-31
• First posted: 2025-07-01
• Last updated: 2025-08-01

Locations

10 sites across 1 country: Spain

Regulatory

• FDA-regulated drug study