Ensayos clínicos

Inclusion Criteria:

• Male or female age ≥ 18 years.
• Prior diagnosis of multiple myeloma according to IMWG criteriaa , and measurable disease.
• Relapsed MM refractory to at least one IMiD, PI, and anti-CD38 antibody; patient does not need to be refractory to all three classes of treatment in the same LOT in order to be eligible.
  • Note: Refractory is defined as having progressive disease (PD) while on therapy or within 60 days following treatment.
  • Note: PD will be defined as one or more of the following based on the 2016 IMWG consensus criteria for response and minimal residual disease assessment in MM:
    • Increase of 25% from lowest confirmed response value in one or more of the following criteria:
    • Serum M-protein (absolute increase must be ≥ 0.5 g/dL);
    • Serum M-protein increase ≥ 1 g/dL, if the lowest M component was ≥ 5 g/dL;
    • Urine M-protein (absolute increase must be ≥ 200 mg/24 h);
    • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be > 10 mg/dL);
    • In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥ 10%);
    • Appearance of a new lesion(s), ≥ 50% increase from nadir in the sum of the products of the maximal perpendicular diameters of measured lesions of > 1 lesion, or ≥ 50% increase in the longest diameter of a previous lesion > 1 cm in short axis; ≥ 50% increase in circulating plasma cells (minimum of 200 cells per µL) if this is the only measure of disease.
• Relapsed or refractory to last anti-MM regimen.
• ECOG performance status ≤ 2.
• Receiving subsequent treatment after becoming TCR (but not necessarily the first subsequent treatment), where initiation of this treatment will define the index date.
• Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
• * If application of International Myeloma Working Group (IMWG) criteria for diagnosis of MM or assessment of response is not available as part of regular clinical practice, clinician assessment may be used. The specific criteria used will be documented in the case report form.

Exclusion Criteria:

• Diagnosis of current smoldering MM, active plasma cell leukemia, amyloidosis, and Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome.
• Prior stem cell transplant within 12 weeks prior to study enrollment or active graft-versus-host-disease (GVHD).
• Any other active malignancy within 3 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• No investigational drug within 30 days or 5 half-lives preceding the index date, and throughout course of the study.
• Prior or concomitant treatment with an anti-BCMA bispecific antibody, including PF-06863135.
• Currently pregnant or breastfeeding.
  • Note: Additional inclusion/exclusion criteria may be applied in a sensitivity analysis to more closely match the Phase 2 MagnetisMM-3 (study C1071003) trial population depending on available data.
• The following information will be collected at the time of enrollment to the extent data are available. Laboratory measurements will be based on the most recent reading at the time of enrollment:
  • Left ventricular ejection fraction (LVEF) > 40% by a multigated acquisition (MUGA) scan or echocardiogram (ECHO);
  • Adequate hepatic function;
  • Total bilirubin < 2 x upper limit of normal (ULN) (< 3 x ULN if documented Gilbert’s syndrome);
  • Aspartate transaminase (AST) < 2.5 x ULN; and
  • Alanine aminotransferase (ALT) < 2.5 x ULN;
  • Adequate renal function;
  • Creatinine clearance > 30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method;
  • Adequate bone marrow function o Absolute neutrophil count (ANC) > 1.0 x 10^9 /L;
  • Platelets > 25 x 10^9 /L; and
  • Hemoglobin > 8 g/dL;
  • Resolved acute effects of any prior therapy to baseline severity or Common Terminology Criteria for Adverse Events (CTCAE) Grade < 1.
• History of impaired cardiovascular function or clinically significant cardiovascular diseases (CVD), defined as any of the following within 6 months prior to study enrollment:
  • Acute myocardial infarction (AMI) or acute coronary syndromes (e.g., unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion);
  • Clinically significant cardiac arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
  • Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism);
  • Prolonged QT syndrome (or triplicate average QTc corrected using Fridericia’s formula [QTcF] > 470 msec at screening);
  • Presence of ongoing Grade > 2 peripheral sensory or motor neuropathy;
  • History of any grade peripheral sensory or motor neuropathy, collected among patients with prior BCMA-directed therapy;
  • History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade > 3 peripheral motor polyneuropathy.
• Presence of surgical (including major surgery within 14 days prior to study enrollment), medical or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the individual inappropriate for the study.
• Presence of active hepatitis B virus (HBV), hepatitis C virus (HCV), SARS-CoV-2, human immunodeficiency virus (HIV), or uncontrolled infection. Active infections must be resolved at least 14 days prior to study enrollment.
• Prior treatment with investigational drug within 30 days or 5 half-lives preceding the index date.

Eligibility last updated 2/14/22. Questions regarding updates should be directed to the study team contact.