A Phase III Study of Elranatamab Versus Lenalidomide in Patients with Newly Diagnosed Multiple Myeloma After Transplantation
Summary description of the study
The aim of the study is to assess whether elranatamab monotherapy compared to lenalidomide monotherapy (control) can provide clinical benefit to patients with newly diagnosed multiple myeloma following autologous stem cell transplantation. A total of approximately 760 patients will be enrolled in the study. The primary endpoint is to compare progression-free survival for elranatamab (arm C) and lenalidomide (arm B) by BICR (central assessment) according to the International Myeloma Working Group (IMWG) for concurrently randomized patients. All participants are expected to receive the study intervention until confirmed disease progression, withdrawal of consent, lost to follow-up, unacceptable toxicity, or study termination. After discontinuation of the study intervention, participants will be followed until withdrawal of consent, lost to follow-up, death, or the defined study end date. followed for survival. The use of elranatamab monotherapy as maintenance is supported by the efficacy results from the Phase I study. Lenalidomide was chosen as the comparator in this study because it is considered the standard of care and the only approved agent in this setting, with its benefit demonstrated in several published studies.
(BASEC)
Intervention under investigation
For the purposes of this protocol, the study intervention refers to elranatamab and lenalidomide.
Elranatamab
Elranatamab is a drug that consists of two antibodies . Elranatamab binds to T cells (a type of immune system cell) and myeloma cells; this causes the T cells to kill the myeloma cells.
Elranatamab is given to participants as a subcutaneous injection by qualified and trained staff at the investigator's site.
Lenalidomide
Lenalidomide is an immune-modulating drug that targets and kills myeloma cells. It helps the immune system recognize and destroy myeloma cells and prevents the growth of new myeloma cells by removing them from the bloodstream.
Participants will be instructed to swallow the study intervention whole and not to chew the capsule before swallowing.
Participants will be randomly assigned in a 1:1 ratio to receive either elranatamab (Arm C) or Lenalidomide (Arm B). The 1:1 ratio means there is a 50% chance of receiving elranatamab or a 50% chance of receiving lenalidomide.
(BASEC)
Disease under investigation
multiple myeloma (newly diagnosed)
(BASEC)
Participation in the study is only possible if all of the following criteria apply Age and gender: 1. Participants aged ≥ 18 years at Visit 1 (screening) or, if applicable, at the pre-screening visit. Type of participants and disease characteristics: 2. Participants who are willing and able to adhere to the scheduled visits, treatment plan, laboratory tests, lifestyle instructions and other study procedures. 3. Multiple myeloma diagnosis as defined by IMWG (International Myeloma Working Group) criteria with measurable disease at diagnosis. 4. Partial response or better according to IMWG (International Myeloma Working Group) criteria at the time of randomization. 5. Identification of the dominant malignant (index) clone, assessed by NGS testing from the central laboratory. 6. ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1. 7. Left ventricular ejection fraction (LVEF) ≥ 40%, determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO). 8. Adequate liver function. 9. Adequate renal function. 10. Adequate recovery of bone marrow function at screening and at randomization after autologous stem cell transplantation. 11. Corrected serum calcium ≤ 14 mg/dL. 12. Resolved acute effects of prior therapy on severity at baseline or CTCAE grade ≤ 1 (CTCAE – common terminology criteria for adverse events). Patient information and consent form: 13. All participants must be able to sign a patient information and consent form as described in Appendix 1. (BASEC)
Exclusion criteria
Participants will be excluded from the study if one or more of the following criteria apply: Diseases: 1. Plasma cell leukemia. 2. Amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome. 3. Known active CNS involvement or clinical signs of myelomatous meningeal involvement 4. Impaired cardiovascular function or clinically significant cardiovascular disease. 5. Persistent Grade ≥ 3 peripheral sensory or motor neuropathy. 6. History of Guillain-Barré syndrome (GBS) or GBS variants or history of Grade ≥ 3 peripheral motor polyneuropathy. 7. Live attenuated vaccine within 4 weeks prior to first dose. 8. Known or suspected hypersensitivity to the study intervention or any of its excipients. 9. Any other active malignancy within three years prior to enrollment, with the exception of an adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ, or stage 0/1 with minimal risk of recurrence as judged by the investigator. 10. Other surgical (including major surgery within 14 days prior to enrollment), medical or psychiatric conditions, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk of study participation or, in the opinion of the investigator, make the patient unsuitable for the study. Previous/concomitant therapy: 11. Previous MM maintenance therapy. 12. Previous treatment with BCMA (B-cell maturation antigen)-targeted therapy. Experience from previous/concomitant clinical trials: 13. Previous administration of an investigational medicinal product or vaccine within 30 days. Diagnostic assessments: 14. Positive (BASEC)
Trial sites
Aarau, Bern, Lausanne, Winterthur, Zurich
(BASEC)
Sponsor
Pfizer Inc. Representative in Switzerland: Pfizer AG
(BASEC)
Contact
Contact Person Switzerland
Martina Knecht Maier
+41 78 615 62 56
martina.knechtmaier@clutterpfizer.comPfizer AG
(BASEC)
General Information
Pfizer
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
07.05.2024
(BASEC)
ICTRP Trial ID
NCT05317416 (ICTRP)
Official title (approved by ethics committee)
A RANDOMIZED, 2-ARM, PHASE 3 STUDY OF ELRANATAMAB (PF 06863135) VERSUS LENALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA AFTER UNDERGOING AUTOLOGOUS STEM-CELL TRANSPLANTATION (BASEC)
Academic title
A RANDOMIZED, 2-ARM, PHASE 3 STUDY OF ELRANATAMAB (PF-06863135) VERSUS LENALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA AFTER UNDERGOING AUTOLOGOUS STEM-CELL TRANSPLANTATION (ICTRP)
Public title
Study With Elranatamab Versus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma After Transplant (ICTRP)
Disease under investigation
Multiple Myeloma (ICTRP)
Intervention under investigation
Drug: ElranatamabDrug: LenalidomideDrug: LenalidomideDrug: Elranatamab (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
- Diagnosis of MM as defined according to IMWG criteria (Rajkumar, 2014) with
measurable disease at diagnosis
- Part 1 patients must be MRD positive, Part 2 patients can be MRD negative or MRD
positive
- History of induction therapy for newly diagnosed MM, followed by high dose therapy
and autologous stem cell transplant. Randomization must occur within 120 days from
the stem cell transplant. For participants who receive consolidation therapy after
ASCT, randomization must occur within 60 days of consolidation and within 7 months
from ASCT.
- Partial Response or better according to IMWG criteria at the time of randomization
- Must have an archival bone marrow aspirate sample(s) to identify the dominant
malignant (index) clone by central laboratory NGS test (ClonoSEQ assay) that is used
to track MRD status. This sample should preferably be collected before induction
treatment (eg, at diagnosis) or before transplant.
- ECOG performance status =1
- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade = 1
- Not pregnant and willing to use contraception
Exclusion Criteria:
- Plasma cell leukemia
- Amyloidosis, Waldenstrm's macroglobulinemia
- POEMS syndrome
- Known active CNS involvement or clinical signs of myelomatous meningeal involvement
- Previous MM maintenance treatment
- Prior treatment with BCMA targeted therapy
- 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
- Active, uncontrolled bacterial, fungal, or viral infection, including (but not
limited to) HBV, HCV, and known HIV or AIDS-related illness
- Previous administration with an investigational 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) (ICTRP)
not available
Primary and secondary end points
Progression Free Survival (ICTRP)
Minimal residual disease Negative rate;Progression Free Survival by BICR per IMWG in IMWG 2025 high-risk participants;PFS by BICR per IMWG in IMWG 2025 standard-risk participant;Overall Survival;MRD-negative rate per IMWG 2025;Sustained MRD negative rate;Progression Free Survival;Overall minimal residual disease negative rate;Duration of minimal residual disease negativity;Sustained minimal residual disease negativity rate;Complete response rate;Duration of complete response;Progression Free Survival 2;Frequency of adverse events;Severity of Cytokine Release Syndrome and Immune effector Cell Associated Neurotoxicity syndrome;Pre-dose concentrations of elranatamab;Post-dose concentrations of elranatamab;Incidence and titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab;Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30;Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20 (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Pfizer CT.gov Call Center;Pfizer CT.gov Call Center, ClinicalTrials.gov_Inquiries@pfizer.com, 1-800-718-1021, Pfizer, (ICTRP)
Secondary trial IDs
MagnetisMM-7, 2023-508897-27-00, C1071007 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT05317416 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available