Clinical Trial 23321

• Overview

  Study Title:

  A Phase 3, Randomized, Open-Label Study to Compare the Efficacy and Safety of Anitocabtagene Autoleucel versus Standard of Care Therapy in Participants with Relapsed/Refractory Multiple Myeloma

  Objective:

  Primary Objective: To compare the efficacy of anitocabtagene autoleucel versus SOCT in participants with RRMM as measured by PFS per blinded IRC Secondary Objectives: To further characterize the efficacy profile of anitocabtagene autoleucel To further characterize the safety profile of anitocabtagene autoleucel To assess patient-reported outcomes associated with anitocabtagene autoleucel compared with SOCT To measure healthcare resource utilization Exploratory Objectives: To characterize the pharmacokinetic profile of anitocabtagene autoleucel in participants with RRMM To characterize anitocabtagene autoleucel pharmacodynamic profiles To determine product characteristics of anitocabtagene autoleucel preinfusion product To evaluate mechanisms of disease response and resistance in RRMM To evaluate efficacy after subsequent line of therapy To evaluate patient-reported treatment tolerability over time To evaluate patient-reported overall disease-related symptoms over time

• Treatments

  Therapies:

  Cell Therapy; Immunomodulators; Therapy (NOS)

  Medications:

  Anitocabtagene autoleucel (); Bortezomib (); CC-4047 (Pomalidomide); Daratumumab (Darzalex); Dexamethasone (); PS-341 (Bortezomib); Pomalidomide (); Velcade (Bortezomib); carfilzomib (Kyprolis); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Documented historical diagnosis of MM.
  • Received 1 to 3 prior lines of antimyeloma therapy, including an IMiD and an anti-CD38 mAb. A minimum of 2 consecutive cycles of an IMiD and an anti-CD38 mAb in any prior line of therapy is required. The IMiD and anti-CD38 mAb do not need to be from the same regimen in the prior line(s) of therapy.
  • Documented evidence of progressive disease by IMWG criteria based on the investigator’s determination on or within 12 months of the last dose of the last regimen.
  • Measurable disease at screening per IMWG, defined as any of the following: Serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio.
  • Only participants who are candidates to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd), as determined by the investigator, should be considered for this study.
  • Male or female aged 18 years or older and who have provided written informed consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate hematological function defined as the following: Hemoglobin count ≥ 7.5 g/dL (without any red blood cell [RBC] transfusion within 7 days prior to the test result; use of recombinant human erythropoietin is permitted). Absolute neutrophil count (ANC) ≥ 500/μL (without non-PEGylated myeloid growth factor support within 7 days or PEGylated myeloid growth factor support within 14 days prior to the test result). Platelet count ≥ 75,000/μL (unless secondary to bone marrow or spleen involvement of MM, in which platelet count ≥ 50,000/μL is permitted) without any platelet cell transfusion within 7 days prior to the test result. Bone marrow involvement by MM is demonstrated by bone marrow aspiration or biopsy. Spleen involvement by MM is demonstrated by splenomegaly. Absolute lymphocyte count (ALC) ≥ 100/μL
  • Adequate renal, hepatic, pulmonary, and cardiac function defined as the following: Estimated glomerular filtration rate (eGFR) (as estimated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation [Section 12.10]) ≥ 45 mL/min. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN. Total bilirubin ≤ 1.5 mg/dL, except in participants with Gilbert’s syndrome or documented MM liver or pancreatic involvement where ≤ 3 x ULN is permitted. Cardiac ejection fraction ≥ 45% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO). Multigated acquisition (MUGA) scan may be used if an ECHO is not available at the site. No evidence of Grade 2 or higher (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) pleural effusion or ascites (participants with Grade 1 pleural effusion or ascites are eligible). Baseline oxygen saturation > 92% on room air.
  • Toxicities due to prior therapy must be stable and recovered to Grade 1 or lower (except for clinically nonsignificant toxicities, such as alopecia and Grade 2 or lower peripheral neuropathy [as per Exclusion Criterion 19)])
  • Females of childbearing potential must have a medically supervised negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential; refer to Section 12.3).
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Prior BCMA-targeted therapy.
  • Prior T-cell engager therapy.
  • Prior CAR therapy or other genetically modified T-cell therapy.
  • Active or prior history of central nervous system (CNS) or meningeal involvement of MM.
  • Cardiac atrial or cardiac ventricular MM involvement.
  • History of or active plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis.
  • Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted.
  • Prior auto-SCT within 12 weeks before randomization.
  • Prior allogeneic stem cell transplant (allo-SCT).
  • Any prior systemic treatment or radiotherapy (even for MM plasmacytoma[s]) for any cancer within 14 days before randomization. mAb treatment is not permitted within 21 days before randomization. Investigational treatments or medical devices are not permitted within 28 days before randomization. Palliative focal radiation for lytic lesions or fractures for pain control of MM is permitted at any time.
  • High-dose (eg, cumulative > 70 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days before randomization.
  • Live vaccine ≤ 4 weeks before randomization.
  • Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if the participant is responding to active treatment and satisfies the criteria of being afebrile (ie, temperature > Acute or chronic active hepatitis A, B, or C infection. Participants with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines.
  • HIV-seropositive.
  • Participants with history or presence of chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) > History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months before randomization.
  • History or presence of intracranial or CNS disorder, such as hemorrhage, dementia, altered mental status, cerebellar disease, or any autoimmune disease with CNS involvement, PRES, or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months before randomization, or seizure disorders requiring active anticonvulsive medication.
  • Peripheral neuropathy of Grade 3 or higher (per CTCAE v5.0; participants with Grade 2 peripheral neuropathy are eligible).
  • History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in or requiring systemic immunosuppression or systemic disease-modifying agents within 2 years.
  • History of concomitant genetic syndrome associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome.
  • Other exclusion criteria may apply.

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