An open label, multicenter, phase II study of Elranatamab as single agent for the treatment of relapsed or refractory myeloma in patients previously exposed to three-drug classes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pethema Fundacion

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

31 Oct 2023 → ongoing

Decision date (initial)

2023-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacogenomic

To evaluate the clinical efficacy of elranatamab in patients with relapsed/refractory multiple myeloma.
Rate of Undetectable Measurable Residual Disease at 6 and 12 months as per International Myeloma Working Group (IMWG) criteria evaluated by the investigators

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 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).
2. 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.
3. 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.
4. Male or female, 18 years or older (at the time consent is obtained).
5. Patient who, in the investigator’s opinion, is able to comply with the protocol requirements.
6. Prior diagnosis of MM as defined according to IMWG criteria.
7. 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
8. Patients must have an ECOG performance status of 0 or 1.
9. Left-ventricular ejection fraction (LVEF) ≥40% (MUGA scan or ECHO).
10. 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).
11. 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)
12. 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.
13. 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.

Exclusion criteria 16

1. 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.
2. Prior anti-BCMA treatment.
3. 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.
4. History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
5. Stem cell transplant within 12 weeks prior to enrolment.
6. Active Graft vs. Host Disease (GVHD) (other than Grade 1 skin involvement), or GVHD requiring treatment.
7. 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.
8. Patients who require administration of live attenuated vaccine within 4 weeks of the first dose of study intervention.
9. 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).
10. 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.
11. Subject has meningeal involvement of multiple myeloma.
12. Pregnant of lactating females.
13. Known human immunodeficiency virus (HIV) infection, active infectious hepatitis A, B or C or chronic hepatitis B or C.
14. 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.
15. 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.
16. Investigational drug within prior 30 days or within 5 half-lives of the investigational drug (whichever is longer).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A participant is considered to have completed the study if he or she is followed until disease progression, withdrawal of consent, loss to follow up, death or end of study.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pethema Fundacion

Sponsor organisation

Pethema Fundacion

Address

Calle Del Professor Martin Lagos Sn

City

Madrid

Postcode

28040

Country

Spain

Scientific contact point

Organisation

Pethema Fundacion

Contact name

Federico Nepote

Public contact point

Organisation

Pethema Fundacion

Contact name

Federico Nepote

Third parties 5

Locations

1 EU/EEA country · 13 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 7 files

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

Application history

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