ELRANATAMAB for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Male or female subjects, 18 years of age or older\n- Men must agree to not father a child and agree to use a latex condom during therapy and for 6 months after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential\n- Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care\n- Subject must have documented multiple myeloma according to International Myeloma Working Group (IMWG) criteria and have received 4 to 6 cycles of quadruplet-based therapy including proteasome inhibitor, IMID and anti CD38 monoclonal antibody\n- Subject must have received only one line of therapy and achieved at least a partial response as per IMWG 2016 criteria.\n- Subject must have received high-dose melphalan and ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT at the time of first treatment dose.\n- Subject must have NGS analysis performed at time of MM diagnosis and/or adequate stored bone marrow material allowing NGS analysis (IUCT-Oncopole, Toulouse, France) in order to calibrate MRD analysis\n- Karnofsky performance status score ≥ 50% (eastern cooperative oncology group performance status ECOG score ≤ 2)\n- Subject must have clinical laboratory values meeting the following criteria during the Screening Phase : Hematology \t•\tHemoglobin >8.0 g/dL without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted) \t•\tPlatelets ≥75×109/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) \t•\tAbsolute neutrophil count ≥1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or 14 days for pegylated-G-CSF) Chemistry \t•\tAST and ALT ≤2.5× upper limit of normal (ULN) \t•\tCrCl ≥30 mL/min based on Cockroft-Gault formula calculation or a 24-hour urine collection \t•\tTotal bilirubin ≤1.5×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤2×ULN is required) \t•\tSerum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L)\n- Women of childbearing potential must have a negative serum or urine pregnancy test within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (One highly effective method and one additional effective method) used at the same time, beginning at least 4 weeks before initiation of lenalidomide treatment and continuing for at least 6 months after the last dose of Lenalidomideor Elranatamab depending on the last treatment taken. Highly effective contraceptive methods are defined as any of the following methods: combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral, intravaginal, transdermal), progestin-only hormonal contraception combined with ovulation inhibition (oral, injectable, implantable), intrauterine device (IUD), hormone-releasing intrauterine system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence. Women must also agree to notify pregnancy during the study."}

Exclusion criteria

• {"criterion_text":"- Subjects have received any prior anti BCMA therapy\n- Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort within 14 days before the first dose of study treatment.\n- Known intolerance to steroid therapy.\n- History of allergy to any of the study medications, their analogues, or excipients in the various formulations.\n- Subject has had major surgery within 2 weeks before randomization or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study. Kyphoplasty or Vertebroplasty are not considered major surgery.\n- Clinically relevant active infection or serious co-morbid medical conditions.\n- Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer free of disease since 5 years.\n- Female subject who is pregnant or breast-feeding.\n- Serious medical or psychiatric illness likely to interfere with participation in study.\n- Uncontrolled diabetes mellitus.\n- Active HBV, HCV, 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. •\tCOVID-19/SARS-CoV-2: SARS-CoV-2 PCR testing is mandated within 5 days prior to enrollment. Participants with positive PCR test result for SARS-CoV-2 within 5 days prior to enrollment, or suspected of having SARS-CoV-2, are excluded. •\tHIV: 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 screening, considering current and past CD4+ and T-cell counts, history (if any) of AIDS defining conditions (eg, opportunistic infections), status of HIV treatment and the potential for drug-drug interactions. •\tHBV: - Participants with a positive HBsAg test (ie, either acute or chronic active hepatitis) are excluded. - 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 negative anti-HBsAb profile are eligible if HBV DNA is not detected. •\tHCV: Positive HCV antibody is indicative of infection but may not necessarily render a potential candidate ineligible, depending on clinical circumstances. If exposure to HCV is recent, HCV antibody may not have yet turned positive. In these circumstances it is recommended to test for HCV RNA. If HCV RNA is detected, the patient is not eligible.\n- Subject have received post transplantation maintenance therapy\n- Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.\n- Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.\n- Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision.\n- Subject intolerant to lenalidomide or having discontinued treatment due to any AE related to lenalidomide\n- Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.\n- Myocardial infarction within 6 months prior to enrollment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.\n- Uncontrolled hypertension\n- Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 < 50% of predicted normal.\n- Subjects with a history of moderate or severe persistent asthma within the past 2 years, or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).\n- Subject has plasma cell leukemia (according to WHO criterion: ≥ 20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the MRD negativity rate (10-6, NGS) status at one year (+/- 1 month) after randomization .","definition_or_measurement_approach":"MRD negativity measured by NGS at 10^-6 sensitivity assessed at one year (+/- 1 month) after randomization."}

Secondary endpoints

• {"endpoint_text":"- rate of MRD [-] status at one year (+/-1month) after randomisation","definition_or_measurement_approach":"MRD status assessed at one year (+/-1 month) after randomization."}
• {"endpoint_text":"- Presence and severity of TEAEs defined by NCI CTCAE Version 5.0 (Number of TEAEs), except for CRS and ICANS, which will be assessed based on ASTCT guidelines. Time frame : Throughout study","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v5.0; CRS and ICANS assessed per ASTCT guidelines; time frame throughout study."}
• {"endpoint_text":"- Rate of MRD [-] status at two years (+/-1month) after randomization. Time frame: MRD assessment at 2 years (+/-1month) after completion","definition_or_measurement_approach":"MRD status assessed by NGS at two years (+/-1 month)."}
• {"endpoint_text":"- Rate of patients with MRD [-] status during at least 12 months (at least two consecutive times) Time frame : 1 year, 2 years","definition_or_measurement_approach":"Sustained MRD negativity defined as MRD [-] for at least 12 months (minimum two consecutive assessments); assessed at 1 and 2 years."}
• {"endpoint_text":"- The rate of complete response or better as defined by IMWG 2016 Time frame : at any time during the study","definition_or_measurement_approach":"Complete response (CR) or better per IMWG 2016 criteria assessed at any time during study."}
• {"endpoint_text":"- OS: time from randomisation to the date of death due to any cause. Subjects alive will be censored at the last date of follow-up.","definition_or_measurement_approach":"Overall survival measured from randomization to death from any cause; censoring at last follow-up for survivors."}
• {"endpoint_text":"- Progression-free survival, defined as the time from randomization to the first occurrence of PD, or death from any cause, whichever occurs first. Subjects alive and for whom disease progression has not been observed will be censored at the last date of follow-up.","definition_or_measurement_approach":"PFS measured from randomization to first PD or death; censoring at last follow-up."}
• {"endpoint_text":"- PFS2: time from randomization to either second line PD (assessed by investigator on the first subsequent line of antimyeloma therapy) or death, whichever occurs first. Subjects alive and for whom a second disease progression has not been observed will be censored at the last date of follow-up.","definition_or_measurement_approach":"PFS2 measured from randomization to second-line progression or death; investigator-assessed."}
• {"endpoint_text":"- Ability of return to work assessed by a specific questionnaire Time frame: At the end of follow-up","definition_or_measurement_approach":"Return-to-work assessed via a specific questionnaire at end of follow-up."}
• {"endpoint_text":"- •\tOutcome: MRD status at 1 year post-randomisation •\tResponse: Complete response at any time during study •\tValue of biological prognostic factors (at diagnosis), such as: •\tISS stage •\tCytogenetics as del(17p), t(4;14), t(14;16), t(14;20), gain(1q), TP53 and del(1p32) •\tTime frame : at diagnosis","definition_or_measurement_approach":"Assess MRD status at 1 year, response status any time, and prognostic biological factors (ISS stage, listed cytogenetic abnormalities) measured at diagnosis."}
• {"endpoint_text":"- Change in EQ-5D-5L and EORTC QC30 score over time Time frame : Screening, Maintenance C1D1, D1 every 3rd cycle, EOT, FU before PD)","definition_or_measurement_approach":"Quality-of-life measured by EQ-5D-5L and EORTC QLQ-C30 at specified timepoints (screening, maintenance cycles, EOT, follow-up before PD)."}

France

Earliest CTIS Part Ii Submission Date

20-02-2025

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

340

Number Of Sites

39

Number Of Participants

176

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Nantes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France