Détails de l'étude

Projet de recherche de phase 3 portant sur l’association du téclistamab au lénalidomide et du téclistamab seul par rapport au lénalidomide seul chez des participants atteints d’un myélome multiple nouvellement diagnostiqué en tant que traitement d’entretien après une greffe autologue de cellules souches. MajesTEC-4

Phase III

Disease Type:
Treatment:
Population:
Première ligne
Immunomodulateur IMiD, Anticorps bispécifique anti-BCMA et anti-CD3
Adultes
  1. ≥18 years of age (and the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
  2. Must have a new diagnosis of symptomatic multiple myeloma according to IMWG criteria (Appendix 4) and have received 4 to 6 cycles of 3- or 4-drug induction therapy that includes a proteasome inhibitor and/or an IMiD with or without anti-CD38 monoclonal antibody and a single or tandem ASCT. Post‑ASCT consolidation is permitted for up to 2 cycles as long as the total number of induction plus consolidation cycles does not exceed 6. Participants must complete all previous treatment prior to screening and at least 7 days prior to randomization (C1D1 for the safety run-in) except for cytotoxic therapy, which must be completed at least 21 days prior to randomization (C1D1 for the safety run-in).
  3. Must have received only one line of therapy and achieved at least a partial response (≥PR) as per IMWG 2016 response criteria based on the investigator’s assessment. Participants with plasmacytomas at the time of diagnosis must meet IMWG 2016 response criteria for ≥PR based on repeat imaging utilizing the same modality
  4. Must not be intolerant to the starting dose of lenalidomide.
  5. Must have received high-dose chemotherapy and ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT (7 months for participants who received consolidation) at the time of randomization or at the time of Sponsor approval for participants in safety run-in.
  6. Must not have received any maintenance therapy.
  7. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 at screening and immediately prior to the start of administration of study treatment.
  8. Have clinical laboratory values meeting the following criteria.

Hematology:

  1. Hemoglobin : ≥8.0 g/dL (≥5 mmol/L; without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted)
  2. Platelets : ≥75×109/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test)
  3. Absolute neutrophil count : ≥0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF or 14 days for pegylated-G-CSF)

Chemistry :

  1. AST and ALT : ≤2.5× upper limit of normal (ULN)
  2. Total bilirubin : ≤1.5×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required)
  3. CrCl : ≥30 mL/min based on Cockcroft-Gault formula calculation (Appendix 8) or a 24‑hour urine collection
  4. Serum calcium corrected for albumin : ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L)
  5. A woman of childbearing potential must have a negative serum pregnancy test within 10‑14 days prior to the start of study treatment and again either a serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
  6. A woman must be:
    1. Not of childbearing potential, or
    2. Of childbearing potential practicing 2 reliable methods of contraception simultaneously including one highly effective method of contraception and one other effective method of contraception starting 4 weeks prior to dosing, throughout the study including during dose interruptions and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 6 months after the last dose of teclistamab, whichever occurs later. For participants who are of childbearing potential, see Section 11.3 for details regarding concomitant use of estrogen-containing products and lenalidomide.

NOTE: If a woman becomes of childbearing potential after start of the study the woman must comply with point (b) as described above.

NOTE: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.

  1. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 6 months after the last dose of teclistamab, whichever occurs later.
  2. A man must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of minimum of 3 months after the last dose of teclistamab, whichever occurs later. If his female partner is of childbearing potential, the male participant must use condom (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception.

NOTE: If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception.

  1. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 3 months after receiving the last dose of teclistamab, whichever occurs later.
  2. Must be willing and able to adhere to the lifestyle restrictions specified in the protocol.
  3. Must sign an informed consent form (ICF) (in accordance with the local requirements) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
  1. Any previous therapy with an immune cell redirecting agent or gene modified adoptive cell therapy (e.g., chimeric antigen receptor modified T cells, NK cells).
  2. Discontinued treatment due to any AE related to lenalidomide as determined by the investigator.
  3. History of allogeneic stem cell transplantation or prior organ transplant.
  4. Progressive disease as per IMWG 2016 response criteria at any time prior to randomization or C1D1 for participants in the safety run‑in.
  5. Radiotherapy within 14 days or focal radiation within 7 days of C1D1.
  6. Received a cumulative dose of corticosteroids equivalent to >40 mg of dexamethasone within the 14 days prior to C1D1.
  7. Received a live, attenuated vaccine within 4 weeks before C1D1. Non-live vaccines or non‑replicating authorized for emergency use (e.g., COVID-19) are allowed.
  8. Excluded for any of the following:
    1. Any ongoing myelodysplastic syndrome or B cell malignancy (other than multiple myeloma)
    2. Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy
    3. Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured:
  • Non-muscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, <3 cm, no CIS)
  • Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone
  • Non-invasive cervical cancer
  • Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer (anti-antihormonal therapy is permitted)
  • Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment)
  • Other malignancy that is considered cured with minimal risk of recurrence in consultation with the Sponsor’s medical monitor.

NOTE: In the event of any questions, consult with the sponsor’s medical monitor prior to enrolling a participant.

  1. Plasma cell leukemia, smoldering multiple myeloma, Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary light chain amyloidosis.
  2. Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required.
  3. Stroke, transient ischemic attack, or seizure within 6 months of C1D1.
  4. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients (refer to IB and most recent applicable RSI).
  5. Participant is pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug.
  6. Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.
  7. Presence of the following cardiac conditions:
    1. New York Heart Association stage III or IV congestive heart failure
    2. Myocardial infarction or coronary artery bypass graft ≤6 months prior to C1D1
    3. History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
    4. Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities.
  8. Any of the following:
  • Human immunodeficiency (HIV) virus-positive participants with 1 or more of the following:
  • History of acquired immune deficiency syndrome (AIDS)-defining conditions
  • CD4 count <350 cells/mm3 at screening
  • Detectable viral load during screening or within 6 months prior to screening
  • Not receiving highly active antiretroviral therapy (ART)
  • Had a change in antiretroviral therapy within 6 months of the start of screening
  • Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Medical Monitor.
  1. Hepatitis B infection (ie, HBsAg or HBV-DNA positive): In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status.
  2. Active hepatitis C infection as measured by positive hepatitis C virus (HCV)- ribonucleic acid (RNA) testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic HCV infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.
  3. Concurrent medical or psychiatric condition or disease, that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study, such as:
    1. Grade 3 or greater peripheral neuropathy
    2. Acute diffuse infiltrative pulmonary disease
    3. Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy
    4. History of autoimmune disease with the exception of:
  1. vitiligo not on systemic therapy
  2. type I diabetes
  • prior autoimmune thyroid disease that is currently euthyroid based on clinical symptoms and laboratory testing
    1. Disabling psychiatric conditions (e.g., alcohol or drug abuse), severe dementia, or altered mental status
    2. Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
    3. History of noncompliance with recommended medical treatments.
  1. Participant had major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or has not fully recovered from an earlier surgery, or has major surgery planned during the time the participant is expected to participate in the study or within 2 weeks after administration of the last dose of study treatment.

NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is a question about whether a procedure is considered a major surgery, the investigator must consult with the sponsor and resolve any issues before enrolling a participant in the study.

  1. Have received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks or 5 PK half-lives, whichever is longer, before C1D1 or is currently enrolled in an interventional investigational study except if only long-term survival data is collected and after Sponsor approval is obtained.

CIUSSS de l’Estrie – CHUS

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