Phase 3 Open-Label Study of Elranatamab vs. Elotuzumab, Pomalidomide, Dexamethasone, or Carfilzomib in Relapsed/Refractory Multiple Myeloma Post Anti-CD38 Therapy
- Trial ID
- 2023-507871-23-00
- Protocol
- C1071032
- Sponsor
- Pfizer Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of **elranatamab** monotherapy (Arm A) against the combination therapies of elotuzumab, pomalidomide, dexamethasone (EPd), pomalidomide, bortezomib, dexamethasone (PVd), or carfilzomib, dexamethasone (Kd) (Arm B) in participants with **relapsed/refractory multiple myeloma** who have previously received anti-CD38 directed therapy. This comparison is clinically relevant as it aims to determine the most effective treatment regimen for this patient population, potentially improving outcomes and guiding future therapeutic strategies.
Secondary objectives include:
- Comparing the efficacy of elranatamab (Arm A) versus EPd, PVd, or Kd (Arm B).
- Determining the safety and tolerability of elranatamab monotherapy.
- Assessing the safety and efficacy of elranatamab in US racial and ethnic minority participants.
- Evaluating the pharmacokinetics (PK) of elranatamab.
- Evaluating the immunogenicity of elranatamab.
- Evaluating the impact of treatment on participant health-related quality of life (HRQoL).
Participants
The clinical trial involves a total of **79 participants** diagnosed with **relapsed/refractory multiple myeloma**. The study population includes both male and female subjects aged 18 years or older, with no upper age limit specified. Participants were selected based on their prior diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) criteria and must have received at least one but not more than four prior lines of therapy, including specific regimens. The trial includes individuals with documented evidence of progressive disease or failure to respond to the last line of therapy. Participants are required to have measurable disease as defined by IMWG criteria and adequate bone marrow function. The trial population is characterized by an **ECOG performance status** of less than 2, indicating a relatively stable general health status. The study does not specify particular lifestyle considerations such as diet or physical activity. The selection process ensures the inclusion of a vulnerable population, reflecting the trial's comprehensive approach to understanding the efficacy of the treatment across diverse patient demographics.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **elranatamab** monotherapy compared to combination therapies in participants with **relapsed/refractory multiple myeloma** who have previously received anti-CD38 directed therapy. This is a Phase 3, open-label study with a randomized, controlled design. The trial is expected to commence recruitment on May 29, 2024, and is estimated to conclude by January 18, 2029. Participants will be randomly assigned to receive either elranatamab or one of the comparator regimens, which include combinations of **elotuzumab**, **pomalidomide**, **dexamethasone**, **bortezomib**, and **carfilzomib**.
The study will involve several key visits, starting with an inclusion (screening) visit to assess eligibility based on criteria such as age, prior treatment history, and disease status. Participants must have a documented diagnosis of multiple myeloma and meet specific laboratory and clinical criteria. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments of progression-free survival (PFS), overall survival (OS), and other secondary endpoints such as objective response rate (ORR) and duration of response (DOR). The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Participant involvement is expected to last up to 55 weeks, depending on the treatment arm and individual response. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. The trial will be conducted under strict adherence to ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.
Treatment
The clinical trial involves the administration of several experimental and non-experimental treatments to participants with **relapsed refractory multiple myeloma**. The primary experimental medication is **ELRANATAMAB**, a solution for injection of biological/biotechnological origin, administered subcutaneously. The maximum daily dose is 76 mg, with a total maximum dose of 5972 mg over a treatment period of 55 days. Participant compliance will be monitored throughout the trial to ensure adherence to the dosing schedule.
Another experimental treatment is **ELOTUZUMAB**, provided as a solution for infusion. This biological medicinal product is administered intravenously, with a maximum daily dose of 20 mg/kg and a total maximum dose of 1120 mg/kg over 55 days. The administration schedule will be closely monitored to ensure participant compliance.
**POMALIDOMIDE** is administered in the form of hard capsules, with available dosages of 1 mg, 2 mg, 3 mg, and 4 mg. This chemical medicinal product is taken orally, with a maximum daily dose of 4 mg and a total maximum dose of 4620 mg over 55 days. Compliance with the oral administration schedule will be monitored.
**DEXAMETHASONE** is provided in tablet form, with dosages of 0.5 mg, 4 mg, and 20 mg. This chemical medicinal product is administered orally, with a maximum daily dose of 40 mg and a total maximum dose of 8800 mg over 55 days. Participant adherence to the dosing schedule will be monitored.
**BORTEZOMIB** is administered as a solution for injection, either subcutaneously or intravenously. This chemical medicinal product has a maximum daily dose of 1.3 mg/m² and a total maximum dose of 211 mg/m² over 55 days. Compliance with the administration route and schedule will be monitored.
**CARFILZOMIB** is provided as a powder for solution for infusion, administered intravenously. This chemical medicinal product has a maximum daily dose of 123 mg and a total maximum dose of 40432 mg over 55 days. Participant adherence to the infusion schedule will be monitored.
**HUMAN NORMAL IMMUNOGLOBULIN** is administered as a solution for infusion, with a maximum daily dose of 2000 mg/kg and a total maximum dose of 110000 mg/kg over a single day. This biological product is administered intravenously, and compliance with the administration schedule will be monitored.
Non-experimental treatments include **FAMOTIDINE**, **VALGANCICLOVIR**, and **ACICLOVIR SODIUM**, all administered orally as chemical medicinal products. These treatments have varying maximum daily doses and treatment periods, with compliance monitored to ensure adherence to the prescribed dosing schedules.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **PFS (progression-free survival)**, which will be evaluated by BICR (blinded independent central review) according to IMWG (International Myeloma Working Group) criteria. Secondary endpoints include OS (overall survival), PFS by Investigator, PFS2 (progression-free survival on the next line of therapy), ORR (objective response rate), DOR (duration of response), VGPRR (very good partial response rate), CRR (complete response rate), DOCR (duration of complete response), and TTR (time to response), all assessed by BICR per IMWG. Additionally, MRD (minimal residual disease) negativity rate and sustained MRD negativity rate for at least 12 months will be evaluated.
Other secondary endpoints include the assessment of AEs (adverse events) and laboratory abnormalities, as well as the pharmacokinetics of elranatamab through pre- and post-dose concentrations. Immunogenicity will be assessed by measuring ADA (antidrug antibody) and NAb (neutralizing antibody) against elranatamab. Patient-reported outcomes will be evaluated using changes from baseline in EORTC QLQ-C30 scores, covering domains such as global health, fatigue, pain, physical functioning, role functioning, and emotional functioning, as well as MY20 scores, which assess disease symptoms, side-effects of treatment, body image, and future perspective.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations if ≥18) at screening.
- Prior diagnosis of MM (multiple myeloma) per IMWG criteria and previously received at least 1 but not more than 4 prior lines of therapy for MM including: • At least 2 consecutive cycles of an anti-CD38 antibody-containing regimen in any prior line AND • At least 2 consecutive cycles of a lenalidomide-containing regimen in any prior line
- 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 (myeloma protein) ≥0.5 g/dL; • Urinary M-protein excretion ≥200 mg/24 hours; • Serum involved immunoglobulin FLC (free light chain) ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
- Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L), or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L)
- Adequate bone marrow function (ANC, platelets, hemoglobin)
- ECOG (Eastern Cooperative Oncology Group) performance status <2.
Exclusion Criteria
- Plasma cell leukemia, Smoldering MM, Waldenström’s macroglobulinemia, Amyloidosis, POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin abnormalities) Syndrome, known CNS (central nervous system) involvement or clinical signs of myelomatous meningeal involvement, stem cell transplant within 12 weeks prior to enrollment, active GVHD (graft versus host disease) (other than Grade 1 skin involvement) or GVHD requiring treatment.
- Active HBV (Hepatitis B virus), HCV (Hepatitis C virus), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), HIV [human immunodeficiency virus], 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.
- Ongoing Grade ≥3 peripheral sensory or motor neuropathy; history of GBS (Guillain-Barré syndrome) or GBS variants; history of any Grade ≥3 peripheral motor polyneuropathy.
- Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment, including LVEF (left ventricular ejection fraction) <40% as determined by a MUGA (multigated acquisition) scan or ECHO (echocardiogram) 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).
- Previous treatment with a BCMA-directed or CD3 (cluster of differentiation 3) redirecting therapy.
- Individuals who have never achieved a response (partial 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 Single Reference Safety Document [SRSD] 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) • Grade 1 peripheral neuropathy with pain or Grade ≥2 peripheral neuropathy as defined by NCI-CTCAE v5.0 • 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 • unable to receive EPd if any of the following are present: • Received prior pomalidomide therapy • Received prior elotuzumab therapy
- 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).
- Live attenuated vaccines within 4 weeks of the first dose of study intervention;
- Cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone (≥21 mg of dexamethasone) within the 14-day period before the first dose of study intervention, and administered for reasons other than anti-myeloma therapy
- Anti-myeloma drug therapy, within 14 days of the initiation of study intervention (includes dexamethasone). Bisphosphonate use permitted.
- Impaired hepatic or renal function.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 29 May 2024 | 20 |
 Croatia | Recruiting | 29 May 2024 | 21 |
 Czechia | Recruiting | 29 May 2024 | 26 |
 Denmark | Recruiting | 29 May 2024 | 12 |
 Finland | Recruiting | 29 May 2024 | 12 |
 France | Recruiting | 29 May 2024 | 59 |
 Germany | Recruiting | 29 May 2024 | 30 |
 Greece | Recruiting | 29 May 2024 | 40 |
 Italy | Recruiting | 29 May 2024 | 52 |
 The Netherlands | Recruiting | 29 May 2024 | — |
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 |
|---|---|---|---|---|---|---|
Bortezomib STADA 2,5 mg/ml Injektionslösung | Comparator | INJEKTIONSLÖSUNG | SUBCUTANEOUS OR INTRAVENOUS | 1.3 | 55 | PRD6601880 |
Dexamethason 0,5 mg JENAPHARM® | Comparator | TABLET | ORAL USE | 40 | 55 | PRD988424 |
Empliciti 400 mg powder for concentrate for solution for infusion. | Comparator | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 20 | 55 | PRD4073310 |
Kyprolis 60 mg powder for solution for infusion | Comparator | POWDER FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 123 | 55 | PRD3374183 |
Privigen 100 mg/ml solution for infusion | Other | SOLUTION FOR INFUSION | INTRAVENOUS USE | 2000 | 1 | PRD339230 |
Privigen 100 mg/ml solution for infusion | Other | SOLUTION FOR INFUSION | INTRAVENOUS USE | 2000 | 1 | PRD339233 |
Imnovid 1 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 4 | 55 | PRD9260804 |
- | Other | PHF00230MIG | INTRAVENOUS USE | 2000 | 1 | J06BA |
Nodexon 20 mg tabletes | Comparator | TABLETĖS | ORAL USE | 40 | 55 | PRD9398502 |
Imnovid 3 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 4 | 55 | PRD9260806 |