IRB Study Number 24-098
Status Recruiting
Phase Phase 3
Institute Taussig Cancer Institute
Description
Primary Objectives
To compare the efficacy of elranatamab (Arm A) vs EPd or PVd or Kd (Arm B)
Secondary Objectives
To compare the efficacy of elranatamab (Arm A) vs EPd or PVd or Kd (Arm B)
To compare the efficacy of elranatamab (Arm A) vs EPd or PVd or Kd (Arm B)
To determine the safety and tolerability of elranatamab monotherapy
To assess the safety and efficacy of elranatamab in US racial and ethnic minority participants
To evaluate the PK of elranatamab
To evaluate immunogenicity of elranatamab
To evaluate the impact of treatment on participant HRQoL
Inclusion Criteria
Age and Sex:
- Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations if ≥18) at screening.
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.
Disease Characteristics:
- Prior diagnosis of MM per IMWG criteria (Rajkumar et al, 2014) and previously received at least 1 but not more than 4 prior lines of therapy for MM including:
(2a) At least 2 consecutive cycles of an anti-CD38 antibody-containing regimen in any prior line AND
(2b) At least 2 consecutive cycles of a lenalidomide-containing regimen in any prior line
See Appendix 16 for quantifying the number of prior lines of therapy.
Documented evidence of progressive disease or failure to achieve a response to last line of MM therapy based on investigator's determination of response by IMWG criteria.
Measurable disease based on IMWG criteria as defined by at least 1 of the following (assessed by central laboratory):
Serum M-protein ≥0.5 g/dL;
Urinary M-protein excretion ≥200 mg/24 hours;
Serum involved immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
- Have clinical laboratory values within the specified range:
Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L), or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L);
ANC ≥1,000/mm3 (use of G-CSFs is permitted if completed at least 7 days prior to eligibility sample collection and at least 7 days prior to planned start of dosing);
Platelet count ≥75,000/mm3 if <50% of BM nucleated cells are plasma cells, or ≥50,000/mm3 if ≥50% of BM nucleated cells are plasma cells (transfusion support is permitted if completed at least 7 days prior to eligibility sample collection and at least 7 days prior to planned start of dosing); and
Hemoglobin ≥8 g/dL (transfusion support is permitted if completed at least 14 days prior to eligibility sample collection and at least 14 days prior to planned start of dosing). Note: ANC, platelets and hemoglobin must meet eligibility criteria on C1D1 prior to proceeding with study treatment.
Other Inclusion criteria:
- ECOG performance status <2.
Exclusion Criteria
Medical Conditions:
- Any surgical (including major surgery within 14 days prior to enrollment), medical or psychiatric condition 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.
- Plasma cell leukemia, Smoldering MM, Waldenström’s macroglobulinemia, Amyloidosis, POEMS Syndrome, known CNS involvement or clinical signs of myelomatous meningeal involvement, stem cell transplant within 12 weeks prior to enrollment, active GVHD (other than Grade 1 skin involvement) or GVHD requiring treatment.
- 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 anti-infective agents is permitted.
(3a) COVID-19/SAR-CoV-2: SARS-CoV-2 PCR testing is mandated within 5 days prior to enrollment. Participants with positive PCR test result for SARSCoV-2 within 5 days prior to enrollment, or suspected of having SARS-CoV-2, are excluded.
(3b) 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 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.
(3c) HBV:
Participants with a positive HBsAg test (eg, 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.
For additional details, refer to CDC website (https://www.cdc.gov/hepatitis-b/hcp/diagnosis-testing/?CDC_AAref_Val=https://www.cdc.gov/hepatitis/hbv/interpretationOfHepBSerologicResults.htm).
See Section 10.18 (HBV screening guide)
(3d) HCV: 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. Refer to CDC website for further details (https://www.cdc.gov/hepatitis/hcv/pdfs/hcv\_graph.pdf).
(3e) Lung imaging is required within 7 days prior to enrollment. Participants with evidence of active respiratory infection are excluded.
- Ongoing Grade ≥ 3 peripheral sensory or motor neuropathy; history of GBS or GBS variants; history of any Grade ≥ 3 peripheral motor polyneuropathy.
- 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);
Known Prolonged QT syndrome (inherited long QT syndrome or QTcF > 470 msec at screening).
LVEF <40% as determined by a MUGA scan or ECHO at screening.
- 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.
- Known or suspected hypersensitivity to the study interventions or any of their excipients.
- Unresolved acute effects (excluding alopecia) of any prior therapy (not resolved to
baseline severity or CTCAE Grade ≤ 1).
Prior/Concomitant Therapy:
- Previous treatment with a BCMA-directed or CD3 redirecting therapy.
- Individuals who have never achieved a response (PR or better) with any treatment during the disease course.
- Unable to receive a control therapy [must be able and willing to adhere to any applicable requirements per SRSD (Section 2.3) for at least one choice of control therapy, including contraceptive requirements, and must not meet the exclusions listed below for the choice of control therapy]:
unable to receive PVd if any of the following are present:
Received prior pomalidomide therapy,
Does not meet criteria for bortezomib retreatment (ie, must not have progressive disease during treatment or within 60 days of the last dose of a bortezomib-containing regimen)
Contraindications or life-threatening allergies, or hypersensitivity to pomalidomide or bortezomib, or intolerance to bortezomib,
Grade 1 peripheral neuropathy with pain or Grade ≥2 peripheral neuropathy as defined by NCI-CTCAE v5,
Received a strong cytochrome P (CYP) 3A4 inducer within 5 half-lives prior to enrollment,
Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery (gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed, assuming no drug interaction potential).
unable to receive Kd if any of the following are present:
Received prior carfilzomib therapy,
Uncontrolled hypertension, defined as an average systolic BP >159 mmHg or diastolic BP >99 mmHg despite optimal treatment,
Grade ≥3 peripheral neuropathy as defined by NCI-CTCAE v5.0,
Contraindications or life-threatening allergies, or hypersensitivity to carfilzomib.
unable to receive EPd if any of the following are present:
Received prior pomalidomide therapy.
Received prior elotuzumab therapy.
Contraindications or life-threatening allergies, or hypersensitivity to elotuzumab /pomalidomide,
Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery (gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed, assuming no drug interaction potential).
- Current use of any prohibited concomitant medication(s) or participants unwilling or unable to use a required concomitant medication(s). Refer to Section 6.9.
Live attenuated vaccines within 4 weeks of the first dose of study intervention;
Cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study intervention;
Anti-myeloma drug therapy, within 14 days of the initiation of study intervention (includes dexamethasone). Bisphosphonate use permitted.
Prior/Concurrent Clinical Study Experience:
- 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). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study. Participants may be eligible 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.
Diagnostic Assessments:
- Hepatic and renal function characterized by the following:
Total bilirubin >1.5 × ULN (> 3 × ULN if documented Gilbert’s syndrome);
AST >2.5 × ULN;
ALT >2.5 × ULN.
24-hour urine collection for creatinine clearance <30 mL/min, or according to local institutional standard method: eGFR <30 mL/min/1.73 m2 using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2021 (serum creatinine only) equation or estimated creatinine clearance <30 mL/min using Cockcroft Gault formula. (If both formulae are calculated, the higher of the two values may be used for eligibility).
Other Exclusion Criteria:
- Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
