Evaluating elranatamab for patients with relapsed or refractory AL amyloidosis

A Phase I/II, Open Label, Study to Evaluate Safety, Tolerability and Efficacy of Elranatamab in Patients With Relapsed or Refractory AL Amyloidosis

This study is testing a new treatment called elranatamab to see if it can help people with relapsed or refractory AL amyloidosis feel better and manage their condition.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Drugs / interventions: belantamab, elranatamab, Daratumumab, CAR-T
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT06569147 on ClinicalTrials.gov

What this trial studies

This Phase I/II clinical trial is designed to assess the safety, tolerability, and efficacy of elranatamab in patients suffering from relapsed or refractory AL amyloidosis. The study will begin with a small group of participants to determine the appropriate dosing levels, followed by a larger cohort if a recommended phase 2 dose is established. Participants will undergo a 28-day evaluation period to monitor for dose-limiting toxicities before proceeding with further dosing cycles. The trial aims to provide insights into the potential benefits of elranatamab for this challenging condition.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of relapsed or refractory AL amyloidosis who have previously undergone at least one line of therapy.

Not a fit: Patients with early-stage AL amyloidosis or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with relapsed or refractory AL amyloidosis.

How similar studies have performed: While this approach is novel for AL amyloidosis, similar studies in other hematologic conditions have shown promising results with targeted therapies.

Eligibility criteria

Inclusion Criteria:

* Previously diagnosed with AL amyloidosis based on IMWG criteria who have relapsed or refractory disease after treatment with at least one prior line of therapy (minimum 2 cycles).
* Participants must have progression of light chain disease, defined as dFLC \>20mg/L.
* For Phase 2 only, measurable hematologic disease, satisfying one of the following criteria: Difference between involved and uninvolved free light chain (FLC) over 40 mg/L; Abnormal level of FLC with an abnormal κ/λ ratio (except in participants with CKD stage 3 or higher where a rise of lambda FLC to an abnormal level and of at least 50% over the nadir with a normal κ/λ ratio is acceptable); A serum M spike measuring ≥ 0.5 g/dL
* Age ≥ 18 years
* ECOG performance status ≤2 or Karnofsky ≥60%
* Participants must meet the following organ and marrow function as defined below: Absolute leukocyte count ≥3,000/mcL , Absolute neutrophil count ≥1,000/mcL, Absolute platelet count ≥75,000/mcL , Direct bilirubin ≤1.5 × institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN, Creatinine: Calculated clearance ≥30 mL/min using Cockcault-Groft equation
* Participants who received belantamab mafodotin are eligible if discontinued due to intolerance or adverse event.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* AL Amyloidosis Cardiac stage I, II or IIIa disease based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in participants with advanced cardiac involvement (Dispenzieri et al., 2004; Wechalekar et al., 2013).
* The effects of elranatamab on the developing human fetus are unknown. Based on the mechanism of action, elranatamab may cause fetal harm when administered to a pregnant woman and therefore should not be used during pregnancy. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and until 90 days since the last dose of elranatamab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of elranatamab administration.
* Ability to understand and the willingness to sign a written informed consent document.
* Willingness to undergo study procedures, including bone marrow biopsies as detailed in the schedule of events.
* Participants should have received prior treatment with Daratumumab + CyBorD.

Exclusion Criteria:

* Prior BCMA-targeting bispecific antibodies or BCMA-targeting CAR-T therapy.
* Participants refractory to belantamab mafodotin OR participants that have received belantamab as the immediate past line of therapy.
* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
* Participants who are receiving any other investigational agents for this condition.
* Participants with Stage IIIB Amyloidosis as defined by the 2004 Mayo Clinic Criteria (see above).
* History of allergic reactions to elranatamab.
* Participants with an active malignancy (including lymphoma) with the following exceptions: adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer; adequately treated stage I cancer from which the patient is currently in remission and has been for over 2 years; low-risk prostate cancer with a Gleason score \< 7 and prostate specific antigen \< 10ng/mL; other localized, indolent and/or low risk cancer may be permitted
* Women who are pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or 4 months following discontinuation of elranatamab, whichever is longer. Pregnant women are excluded from this study because elranatamab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with elranatamab, breastfeeding should be discontinued if the mother is treated with elranatamab.
* Have any other medical, social or psychological factors that could affect the participant's safety or ability to consent personally or comply with study procedures.
* Participants meeting criteria for active MM based on presence of CRAB criteria (a ratio of involved versus uninvolved FLC over 100 is allowed in the absence of CRAB criteria).
* Participants with active clinically significant autoimmune diseases.
* Participants seropositive for the human immunodeficiency virus (HIV).
* Severe, uncontrolled orthostatic hypotension resulting in syncopal/pre-syncopal events despite optimized medical management (e.g., midodrine, pyridostigmine) and in the absence of volume depletion.
* Plan for autologous stem cell transplant during the first 6 months of protocol therapy.
* History of acute coronary syndrome or uncontrolled ventricular arrhythmias within 3 months prior to screening.
* Evidence of LV systolic dysfunction as defined by LVEF is \< 30% by echocardiogram at Screening per site cardiology interpretation.
* Presence of severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area \< 1.0 cm2) or severe congenital heart disease.
* Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction if a permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) is not placed.
* QT corrected by Fridericia (QTcF) is \> 550 msec on Screening ECG unless they have a PPM/ICD implanted.
* Screening EKG showing acute myocardial ischemia or active conduction system abnormalities with the exception of any of the following: First degree atrioventricular block; Second degree atrioventricular block Type 1 (Mobitz Type 1/Wenckebach type); Right or left bundle branch block (e.g., Left Bundle Branch Block, Right Bundle Branch Block, Left Anterior Fascicular Block, or Left Posterior Fascicular Block); Atrial fibrillation with a controlled ventricular rate; Bifascicular block assessed as benign by the Investigator
* Major surgery that required general anesthesia within 4 weeks of randomization or is planning major surgery during the study.
* NYHA class IV symptoms or participants with acute decompensation of congestive heart failure.
* Transplant eligible participants who have not undergone transplant are not eligible.

Where this trial is running

Boston, Massachusetts

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Giada Bianchi — Dana-Farber Cancer Institute
• Study coordinator: Giada Bianchi

Conditions AL Amyloidosis