A Phase 3 Study With Elranatamab Versus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma After Transplant

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Apr 2022 → ongoing

Decision date (initial)

2024-04-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-508897-27-00

EudraCT number

2021-006052-14

ClinicalTrials.gov

NCT05317416

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of elranatamab versus lenalidomide

Secondary objectives 1

1. • To compare the efficacy of elranatamab versus lenalidomide • To determine the safety and tolerability of elranatamab • To evaluate the PK of elranatamab • To evaluate the immunogenicity of elranatamab • To evaluate the impact of study intervention on participant healthrelated quality of life (HRQoL)

Conditions and MedDRA coding

Multiple Myeloma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003083-PIP01-21

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. 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
2. 2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3. 3. 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.
4. 4. PR or better according to IMWG criteria at the time of randomization.
5. 5. Identification of the dominant malignant (index) clone as assessed by central laboratory NGS test (Adaptive Biotechnologies clonoSEQ® assay.
6. 6. ECOG performance status ≤1.
7. 7. Left ventricular ejection fraction (LVEF) ≥40% as determined by a multigated acquisition (MUGA) scan or echocardiogram (ECHO).
8. 8. 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.
9. 9. 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.
10. 10. 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).
11. 11. Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L).
12. 12. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
13. 13. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion criteria 10

1. 1. Plasma cell leukemia defined as more than 20% circulating plasma cells and an absolute count >2 × 109/L plasma cells in peripheral blood)
2. 2. Amyloidosis, Waldenström’s macroglobulinemia, or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome.
3. 3. Known active central nervous system (CNS) involvement or clinical signs of myelomatous meningeal involvement
4. 4. 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.
5. 5. Ongoing Grade ≥3 peripheral sensory or motor neuropathy.
6. 6. History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
7. 7. Live attenuated vaccine within 4 weeks of the first dose.
8. 8. Known or suspected hypersensitivity to the study interventions or any of its excipients.
9. 9. 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.
10. 10. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1.  Progression-free survival (PFS) by Blinded Independent Central Review (BICR) per International Myeloma Working Group (IMWG)

Secondary endpoints 1

1. Minimal residual disease (MRD)-negative rate at 12 months after randomization per IMWG as assessed via next-generation sequencing (NGS) • PFS by BICR per IMWG in IMWG 2025 high-risk participants • PFS by BICR per IMWG in IMWG 2025 standard-risk participants • Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 13

Locations

14 EU/EEA countries · 83 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 219 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications