Phase II Multicenter Study of Elranatamab Monotherapy in Relapsed/Refractory Multiple Myeloma Post-Three Drug Class Exposure

Trial ID: 2023-504273-21-00
Sponsor: Fundacion PETHEMA

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Diseases & Conditions

Plasma cell myeloma

Objectives

The primary objective of this study is to evaluate the clinical efficacy of **elranatamab** in patients with relapsed or refractory **multiple myeloma** who have been previously exposed to three-drug classes. The study aims to determine the rate of undetectable measurable residual disease at 6 and 12 months, as per the International Myeloma Working Group (IMWG) criteria, evaluated by the investigators. This is clinically relevant as achieving undetectable residual disease is associated with improved patient outcomes and prolonged survival in multiple myeloma.

Participants

The clinical trial focuses on evaluating the efficacy of elranatamab in patients with **relapsed/refractory multiple myeloma**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a prior diagnosis of multiple myeloma and must have received one or two prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. The trial does not involve a vulnerable population. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a left-ventricular ejection fraction of at least 40%. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified. The selection criteria ensure that participants have measurable secretory disease and meet specific laboratory value thresholds. The trial population was selected based on the ability to comply with protocol requirements and the provision of informed consent.

Plans and Procedures

The clinical trial is a **Phase II** study designed to evaluate the efficacy of **elranatamab** as a monotherapy for patients with relapsed or refractory **multiple myeloma** who have been previously treated with immunomodulatory drugs, protease inhibitors, and anti-CD38 therapy. The trial is open-label and multicenter, with an estimated completion date of December 31, 2029. Participants will receive a subcutaneous injection of elranatamab at a dose of 76 mg. The primary objective is to assess the rate of undetectable measurable residual disease at 6 and 12 months, as per the International Myeloma Working Group criteria.

The trial design includes an initial screening visit to confirm eligibility based on specific inclusion criteria, such as prior exposure to certain drug classes and measurable secretory disease. Participants must also meet laboratory value thresholds and have an Eastern Cooperative Oncology Group performance status of 0 or 1. Following the screening, eligible participants will enter the treatment phase, which involves regular follow-up visits to monitor efficacy and safety outcomes. These visits will include assessments of disease progression and response to treatment.

The expected duration of participant involvement is up to 12 months, with the possibility of early termination due to disease progression, withdrawal of consent, loss to follow-up, or adverse events. The end-of-study visit will occur upon completion of the treatment period or earlier if the participant meets any criteria for study discontinuation. Throughout the trial, participants will be closely monitored to ensure compliance with protocol requirements and to evaluate the clinical efficacy of elranatamab in this patient population.

Treatment

The clinical trial involves the administration of **Elranatamab**, a pharmaceutical product developed by Pfizer Inc. **Elranatamab** is formulated as a **solution for injection** and is classified as a protein-based therapeutic agent. The active substance, **Elranatamab**, is derived from a protein of other origin. The medication is administered via the **subcutaneous route**. The dosing regimen specifies a maximum daily dose of 76 mg, with the total dose not exceeding 76 mg per day. The treatment period is capped at 12 months. The trial is designed to evaluate the efficacy of **Elranatamab** in patients with relapsed or refractory multiple myeloma who have been previously exposed to three-drug classes.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is structured as an open-label, multicenter, phase II study, focusing solely on the administration of **Elranatamab** as a single agent. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The primary objective is to assess the rate of undetectable measurable residual disease at 6 and 12 months, as per the International Myeloma Working Group (IMWG) criteria, evaluated by the investigators.

Efficacy

The clinical trial aims to evaluate the efficacy of **elranatamab** in patients with relapsed or refractory multiple myeloma. The primary endpoint for assessing efficacy is the rate of undetectable measurable residual disease at 6 and 12 months, as per the International Myeloma Working Group (IMWG) criteria. This will be evaluated by the investigators. The study is designed as an open-label, multicenter, phase II trial, focusing on patients who have been previously exposed to three-drug classes, including immunomodulatory drugs, protease inhibitors, and anti-CD38 therapy.

Participants will receive elranatamab as a single agent, administered subcutaneously at a dose of 76 mg. The trial will monitor the participants until disease progression, withdrawal of consent, loss to follow-up, death, or the end of the study. The efficacy assessments will be conducted at specified intervals, particularly at 6 and 12 months, to determine the rate of complete response and undetectable measurable residual disease. The trial is expected to conclude by December 31, 2029.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Relapse multiple myeloma patients that have received 1 or 2 prior lines of therapy including at least to one proteasome inhibitor (bortezomib, carfilzomib or ixazomib), one immunomodulatory drug (lenalidomide is mandatory and patients can be also have been exposed to pomalidomide) and at least one anti-CD38 monoclonal antibody (daratumumab or isatuximab).
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.
Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients in whom disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/L (100 mg/dl), with an abnormal serum FLC ratio.
Male or female, 18 years or older (at the time consent is obtained).
Patient who, in the investigator’s opinion, is able to comply with the protocol requirements.
Prior diagnosis of MM as defined according to IMWG criteria.
Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
Patients must have an ECOG performance status of 0 or 1.
Left-ventricular ejection fraction (LVEF) ≥40% (MUGA scan or ECHO).
Subject must have pretreatment clinical laboratory values meeting the following criteria during the Screening Phase: hemoglobin ≥8 g/dL; absolute neutrophil count (ANC) ≥ 1.0 x 109/L; platelet count ≥ 25 x109/L; aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) ≤2.5 x ULN; total bilirubin ≤2 x ULN, except in subjects with congenital hyperbilirubinemia, such as Gilbert syndrome (bilirubin ≤3 x ULN); estimated creatinine clearance > 30 mL/min/1.73 m2; corrected serum calcium <14 mg/dL (<3.5 mmol/L); or free ionized calcium <6.5 mg/dL (<1.6 mmol/L).
Women of childbearing potential must be using a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies (see Appendix 13)
Women of childbearing potential must have a negative serum pregnancy test at screening within 10-14 days and 24 hours before starting treatment. Females of reproductive potential must agree either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control simultaneously.
Male Participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 100 days: refrain from donating sperm PLUS either: be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR must agree to use contraception/barrier.

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Exclusion Criteria

Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), POEMS syndrome (defined by the presence of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma-cells proliferative disorder, and skin changes) or plasma cell leukemia.
Prior anti-BCMA treatment.
Subject has peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.
History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
Stem cell transplant within 12 weeks prior to enrolment.
Active Graft vs. Host Disease (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. Patients whose HIV or HCV status cannot be determined from their medical history must be screened for HIV and HCV up to 28 days prior to enrollment.
Patients who require administration of live attenuated vaccine within 4 weeks of the first dose of study intervention.
Prior history of malignancies other than MM, unless the subject has been free of the disease for > 2 years. Exceptions include: basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
Impaired cardiovascular function and/or clinically significant cardiovascular diseases, defined as any of the following within 6 months: acute myocardial infarction, acute coronary syndromes (e-g- unstable angina, coronary artery bypass graft, coronary angioplasty or stenting); clinically significant cardiac arrhythmias (e.g. uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); thromboembolic or cerebrovascular events (e.g. transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism); QTcF interval ≥470 msecs.
Subject has meningeal involvement of multiple myeloma.
Pregnant of lactating females.
Known human immunodeficiency virus (HIV) infection, active infectious hepatitis A, B or C or chronic hepatitis B or C.
Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) not mentioned above that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
Subject who received any of the following within the last 14 days of initiation of study treatment: major surgery (except patients recovered from kyphoplasty) or use of any anti-myeloma drug therapy.
Investigational drug within prior 30 days or within 5 half-lives of the investigational drug (whichever is longer).