Phase 3 Randomized Study of Elranatamab Versus Lenalidomide in Patients with Newly Diagnosed Multiple Myeloma Post-Autologous Stem-Cell Transplantation
- Trial ID
- 2023-508897-27-00
- Protocol
- C1071007
- Sponsor
- Pfizer Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 study is to compare the **efficacy** of **elranatamab** versus **lenalidomide** in patients with newly diagnosed **multiple myeloma** following autologous stem-cell transplantation. This comparison is clinically relevant as it aims to determine the most effective treatment option for improving patient outcomes in this specific population.
Secondary objectives include:
- Comparing the efficacy of elranatamab versus lenalidomide.
- Determining the safety and tolerability of elranatamab.
- Evaluating the pharmacokinetics (PK) of elranatamab.
- Assessing the immunogenicity of elranatamab.
- Evaluating the impact of the study intervention on participants' health-related quality of life (HRQoL).
Participants
The clinical trial involves a total of **383 participants** diagnosed with **Multiple Myeloma**, a hematological malignancy. The study population includes both male and female subjects, aged 18 years and older, who are capable of providing informed consent. Participants were selected based on their ability to comply with the study's requirements, including scheduled visits and treatment plans. The trial population is characterized by adequate recovery of bone marrow function post-autologous stem cell transplantation, as well as sufficient hepatic and renal function. Lifestyle considerations such as diet and physical activity are not specified. The trial includes a vulnerable population, indicating that additional ethical considerations are in place to protect these participants. Key inclusion criteria ensure that participants have a measurable disease and meet specific health status requirements, such as an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a left ventricular ejection fraction of at least 40%. The trial aims to compare the efficacy of elranatamab versus lenalidomide in this patient population.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy of **elranatamab** versus **lenalidomide** in patients with newly diagnosed **multiple myeloma** following autologous stem-cell transplantation. The trial is a Phase III therapeutic confirmatory study, with an estimated duration extending until October 31, 2029. Participants will be randomly assigned to receive either elranatamab via subcutaneous injection or lenalidomide in the form of oral hard capsules. The primary endpoint is progression-free survival as assessed by a blinded independent central review, while secondary endpoints include overall survival.
The study involves a sequence of visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, adequate post-transplant recovery, and measurable disease according to International Myeloma Working Group criteria. Following randomization, participants will undergo regular follow-up visits to monitor treatment response, safety, and adherence to the protocol. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and any long-term effects of the treatment.
Participant involvement is expected to last up to six months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or failure to comply with study procedures. The trial aims to provide robust data on the comparative efficacy of the investigational product versus the control, contributing to the understanding of treatment options for multiple myeloma.
Treatment
The clinical trial involves the administration of several treatments, including **elranatamab**, **lenalidomide**, and **human normal immunoglobulin**. **Elranatamab** is provided as a solution for injection, with a maximum daily dose of 76 mg and a total dose limit of 3980 mg over a treatment period of up to 6 months. It is administered via subcutaneous injection. This investigational drug, identified by the sponsor product code PF-06863135, is of biological/biotechnological origin and is designated as an orphan drug. The product is manufactured by Pfizer Inc.
**Lenalidomide** is available in three different dosages: 5 mg, 10 mg, and 15 mg, all in the form of hard capsules. The maximum daily dose for lenalidomide is 15 mg, with a total dose limit of 8400 mg over a 6-month treatment period. The capsules are administered orally. The product is chemically synthesized and is provided by Adalvo Limited. The lenalidomide capsules are used as a comparator in the study.
**Human normal immunoglobulin** is administered as a solution for infusion, with a concentration of 100 mg/ml. The maximum daily and total dose is 4.8 ml, administered via intravenous infusion. This product is derived from blood and is manufactured by CSL Behring GmbH. It serves as an auxiliary treatment in the trial.
Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed treatment regimens. The trial aims to compare the efficacy of elranatamab versus lenalidomide in patients with newly diagnosed multiple myeloma following autologous stem-cell transplantation.
Efficacy
The efficacy of the clinical trial comparing **elranatamab** versus **lenalidomide** in patients with newly diagnosed multiple myeloma post-autologous stem-cell transplantation will be assessed using specific endpoints. The primary endpoint for evaluating efficacy is Progression-Free Survival (PFS), which will be determined by Blinded Independent Central Review (BICR) according to the International Myeloma Working Group (IMWG) criteria. Additionally, the secondary endpoint includes Overall Survival (OS).
Data collection and analysis will be conducted at predetermined intervals throughout the trial duration, which is estimated to conclude by October 31, 2029. The trial commenced recruitment on April 28, 2022. The efficacy parameters will be measured using validated scales and laboratory tests, ensuring adherence to the IMWG criteria for consistency and reliability in the assessment of disease progression and survival outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant’s age ≥18 years (or the minimum country specific age of consent if >18) at Visit 1 (Screening), or at the pre-screening visit, as applicable. - Male participants and female participants of childbearing potential must agree to use contraception
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- Diagnosis of MM as defined according to IMWG criteria1 with measurable disease at diagnosis as defined by serum M-protein ≥0.5 g/dL (5 g/L), by urine M-protein ≥200 mg/24 hours, or by serum free light chain (FLC) assay with involved FLC level ≥10 mg/dL, provided serum FLC ratio is abnormal.
- PR or better according to IMWG criteria at the time of randomization.
- Identification of the dominant malignant (index) clone as assessed by central laboratory NGS test (Adaptive Biotechnologies clonoSEQ® assay.
- ECOG performance status ≤1.
- Left ventricular ejection fraction (LVEF) ≥40% as determined by a multigated acquisition (MUGA) scan or echocardiogram (ECHO).
- Adequate hepatic function characterized by the following: - Total bilirubin ≤2 × upper limit of normal (≤3 × ULN if documented Gilbert’s syndrome and direct bilirubin ≤ ULN); - Aspartate aminotransferase (AST) ≤2.5 × ULN; and - Alanine aminotransferase (ALT) ≤2.5 × ULN.
- Adequate renal function defined according to local institutional standard method: estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation or estimated creatinine clearance (CrCl) ≥30 mL/min using Cockcroft Gault formula. If both formulae are calculated, the higher of the 2 values may be used. A 24-hour urine collection for CrCl may also be used in equivocal cases where amyloidosis is suspected.
- Adequate post-ASCT recovery of BM function at screening and randomization as characterized by the following: - Absolute neutrophil count (ANC) ≥1.0 × 109/L (use of granulocyte colonystimulating factor [G-CSF] is permitted if completed at least 7 days prior to planned start of dosing; G-CSF should not be used to reach this level); - Platelets ≥75 × 109/L (transfusion support is permitted if completed 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 planned start of dosing).
- Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L).
- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
Exclusion Criteria
- Plasma cell leukemia defined as more than 20% circulating plasma cells and an absolute count >2 × 109/L plasma cells in peripheral blood)
- Amyloidosis, Waldenström’s macroglobulinemia, or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome.
- Known active central nervous system (CNS) involvement or clinical signs of myelomatous meningeal involvement
- Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment: - Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic 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 time from the beginning of the Q wave to the end of the T wave (QT) syndrome or QT corrected using Friderica’s formula (QTcF) >470 msec at screening.
- Ongoing Grade ≥3 peripheral sensory or motor neuropathy.
- History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- Live attenuated vaccine within 4 weeks of the first dose.
- Known or suspected hypersensitivity to the study interventions or any of its excipients.
- 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 with minimal risk of recurrence per the investigator.
- Other 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 28 Apr 2022 | 2 |
 Belgium | Not Recruiting | 28 Apr 2022 | 22 |
 Czechia | Not Recruiting | 28 Apr 2022 | 55 |
 Finland | Not Recruiting | 28 Apr 2022 | 18 |
 France | Not Recruiting | 28 Apr 2022 | 33 |
 Germany | Not Recruiting | 28 Apr 2022 | 25 |
 Greece | Not Recruiting | 28 Apr 2022 | 24 |
 Hungary | Not Recruiting | 28 Apr 2022 | 20 |
 Italy | Not Recruiting | 28 Apr 2022 | 35 |
 The Netherlands | Not Recruiting | 28 Apr 2022 | — |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Zelvina 15 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 15 | 6 | PRD8721724 |
Privigen 100 mg/ml solution for infusion | Other | SOLUTION FOR INFUSION | IV INFUSION | 4.8 | 6 | PRD339233 |
ELRANATAMAB | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 76 | 6 | PRD10297333 |
Zelvina 5 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 15 | 6 | PRD8721745 |
Zelvina 10 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 15 | 6 | PRD8721704 |