Détails de l'étude

MagnetisMM-30 Étude ouverte de phase 1b visant à évaluer l’elranatamab en association avec l’iberdomide chez des participants atteints d’un myélome multiple en rechute ou réfractaire.

Phase 1b

Type de maladie :
Traitement :
Population :
Rechute et réfractaire : Part 1 – 3e à 5e lignes et Part 2 : 2e à 4e lignes
Immunomodulateur IMiD, Anticorps bispécifique anti-BCMA et anti-CD3
Adultes
  1. Participant age ≥18 years at the time of informed consent.
  2. Prior diagnosis of MM as defined according to IMWG criteria as defined by at least 1 of the following:
    1. Serum M-protein ≥0.5 g/dL by SPEP
    2. Urinary M-protein excretion ≥200 mg/24 hours by UPEP
    3. Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FL ratio (0.26 or >1.65)
  3. PART 1: Participants who have received at least 2 and not more than 4 prior lines of therapy for MM including:
  • At least 1 IMiD (lenalidomide or pomalidomide)
  • At least 1 PI
  • All participants in PART 1 must have received prior treatment with at least 2 consecutive cycles of a lenalidomide or pomalidomide-containing regimen and at least 2 consecutive cycles of a PI or a PI-containing regimen
  1. PART 2: Participants who have received at least 1 but not more than 3 prior lines of therapy for MM including:
    • At least IMiD (lenalidomide or pomalidomide)
    • At least 1 PI
    • All participants in PART 2 must have received prior treatment with at least 2 consecutive cycles of a lenalidomide or pomalidomide-containing regimen and at least 2 consecutive cycles of a PI or a PI-containing regimen (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy)
  2. Relapsed or Refractory to the last anti-MM regimen according to IMWG criteria.
    1. Refractory MM is defined as having disease progression while on therapy or within 60 days of last dose in any line. Relapsed MM is the recurrence of disease after a prior response, as defined by the IMWG criteria for clinical relapse evidenced by markers of increasing disease burden and/or end-organ dysfunction.
    2. Primary refractory MM defined as participants who have never achieved at least a MR with any treatment during the disease course are not eligible
  3. LVEF ≥40% as determined by a MUGA scan or ECHO
  4. ECOG performance status 0-1.
  5. Adequate hepatic function defined by the following:
    1. Total bilirubin ≤1.5 × ULN (≤3 × ULN if documented Gilbert’s syndrome)
    2. AST ≤2.5 × ULN
    3. ALT ≤2.5 × ULN
  6. Adequate renal function defined by 24-hour urine collection for creatinine clearance ≥30 mL/min, or according to local institutional standard method: de-indexed eGFR ≥30 mL/min using CKD-EPI 2021 (serum creatinine only) equation or estimated creatinine clearance ≥30 ml/min using Cockcroft Gault formula, whichever is higher.
  7. Adequate bone marrow function characterized by the following:
    1. ANC ≥1000/mm3 (use of G-CSFs is permitted if completed at least 7 days prior to planned start of dosing)
    2. Platelets ≥75 × 109/L (≥50 × 109/L if myeloma involvement in the bone marrow is ≥50%) (transfusion support is permitted if completed at least 7 days prior to planned start of dosing)
    3. Hemoglobin ≥8 g/dL (transfusion support is permitted if completed at least 14 days prior to planned start of dosing).
  8. Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L).
  9. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.

. Participants with any of the following medical conditions:

  • Plasma cell leukemia, Smoldering MM, Waldenström’s macroglobulinemia, Amyloidosis, POEMS Syndrome.
  • Known CNS involvement or clinical signs of myelomatous meningeal involvement.
  • Active GVHD, history of stem cell transplant within 12 weeks prior to enrollment.
  1. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment:
  • Acute myocardial infarction, acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, pericardial effusion);
  • Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
  • Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism);
  • Prolonged QT syndrome (or QTcF >470 msec at screening).
  1. Ongoing Grade ≥2 peripheral sensory or motor neuropathy
  2. History of GBS or GBS variants, or history of anyGrade ≥3 peripheral motor polyneuropathy.
  3. Participants with active HBV, HCV, COVID-19/SARS-CoV-2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 21 days prior to enrollment. Treatment with systemic anti-infective agents must have completed at least 28 days prior to enrollment. Prophylactic use of systemic agents is permitted.
  4. COVID-19/SARS-CoV-2: COVID-19/SARS-CoV-2 PCR testing is mandated within 5 days prior to enrollment. Participants with a positive PCR test result for COVID-19/SARS-CoV-2 within 5 days prior to enrollment or those suspected of having COVID-19/SARS-CoV-2 should be excluded from study enrollment.
  5. HIV: In equivocal cases, participants whose viral load is negative may be eligible. HIV seropositive participants who are otherwise healthy and at low risk for AIDS-related outcomes could be considered eligible. Potential eligibility for a specific HIV positive protocol candidate should be evaluated and discussed with the Sponsor prior to any screening, based on current and past CD4 and T-cell counts, history (if any) of AIDS defining conditions (eg, opportunistic infections), and status of HIV treatment. Also, the potential for drug-drug interactions will be taken into consideration.
  6. HBV/HCV: Relevant laboratory tests should be performed at screening.
  7. HBV:
    • This criterion excludes participants with a positive HBsAg (ie, either acute or chronic active hepatitis).
    • However, participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are eligible.
    • Participants with positive anti-HBcAb but negative HBsAg and anti-HBsAb profile are eligible if HBV DNA is not detected.
  8. HCV: Positive HCV antibody is indicative of infection but may not necessarily render a potential participant ineligible, depending on clinical circumstances. If exposure to HCV is recent, HCV antibody may not have yet turned positive. In this circumstance it is recommended to test HCVRNA.
  9. Lung imaging (eg., chest x-ray or lung CT) is required within 7 days prior to enrollment. Participants with evidence of active respiratory infection are excluded.
  10. Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ or Stage 0/1 malignancy with minimal risk of recurrence per investigator.
  11. Gastrointestinal disease that may significantly alter the absorption of iberdomide.
  12. Other surgical (including major surgery within 14 days prior to 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 participant inappropriate for the study.
  13. Previous treatment with either:
  • BCMA-directed or CD3 redirecting therapy
  • Iberdomide (CC-220) or Mezigdomide
  1. Bridging treatment prior to the first dose of study intervention
  2. Participants with:
  • Known or suspected hypersensitivity to the study drug intervention(s) or any of its excipients.
  • History of anaphylaxis or severe hypersensitivity to thalidomide, lenalidomide, or pomalidomide.
  • Intolerance to or participants who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or therapeutic proteins.
  1. Strong inhibitor or inducer of CYP3A4/5 including grapefruit, St John’s Wort or related products within 2 weeks prior to dosing and during the course of study
  2. Live attenuated vaccines within 4 weeks of the first dose of study intervention.
  3. Participant receives a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study intervention.
  4. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). A participant may be eligible even if they are in the follow-up phase of an investigational study if they meet the criterion for time elapsed from previous administration of investigational product. Cases must be discussed with sponsor’s medical monitor to judge eligibility.
  5. Participant unable or unwilling to undergo protocol required thromboembolism prophylaxis.
  6. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

CIUSSS de l’Estrie – CHUS

CIUSSS de l’Est-de-L’Île-de-Montréal – Hôpital Maisonneuve-Rosemont

Autres études

MonumenTAL-6 :Étude de phase 3 avec répartition aléatoire comparant le talquétamab en association avec la pomalidomide (Tal-P), le talquétamab en association avec le téclistamab (Tal-Tec) et une association choisie par l’investigateur composée d’élotuzumab, de pomalidomide et de dexaméthasone (EPd) ou de pomalidomide, de bortézomib et de dexaméthasone (PVd), chez des participants atteints d’un myélome récidivant ou réfractaire ayant déjà reçu de 1 à 4 traitements comprenant un anticorps anti-CD38 et de la lénalidomide