ELRANATAMAB for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1. Male or female participants age ≥18 years. • A female participant is eligible to participate if she is not pregnant or breastfeeding.\n- 2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.\n- 3. Prior diagnosis of MM as defined according to IMWG criteria.\n- 4. Measurable disease based on IMWG criteria as defined by at least 1 of the following: a. Serum M-protein >0.5 g/dL by SPEP b. Urinary M-protein excretion >200 mg/24 hours by UPEP c. Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).\n- 5. Refractory to at least one IMiD.\n- 6. Refractory to at least one PI.\n- 7. Refractory to at least one anti-CD38 antibody.\n- 8. Relapsed or refractory to last anti-MM regimen. Note: Refractory is defined as having disease progression while on therapy or within 60 days of last dose in any line, regardless of response.\n- 9. Cohort A: Has not received prior BCMA-directed therapy. Cohort B: Has received prior BCMA-directed ADC or BCMA-directed CAR T-cell therapy, either approved or investigational.\n- 10. ECOG performance status ≤2.\n- 11. LVEF ≥40% as determined by a MUGA scan or ECHO.\n- 12. Adequate hepatic function characterized by the following: a. Total bilirubin ≤2 x ULN (≤3 x ULN if documented Gilbert’s syndrome); b. AST ≤2.5 x ULN; and c. ALT ≤2.5 x ULN.\n- 13. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method).\n- 14. Adequate BM function characterized by the following: a. ANC ≥1.0 × 109/L (use of granulocyte-colony stimulating factors is permitted if completed at least 7 days prior to planned start of dosing); b. Platelets ≥25 × 109/L (transfusion support is permitted if completed at least 7 days prior to planned start of dosing); and c. Hemoglobin ≥8 g/dL (transfusion support is permitted if completed at least 7 days prior to planned start of dosing).\n- 15. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.\n- 16. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol."}

Exclusion criteria

• {"criterion_text":"- 1. Smoldering MM.\n- 7. Ongoing Grade ≥2 peripheral sensory or motor neuropathy.\n- 8. History of any grade peripheral sensory or motor neuropathy with prior BCMA-directed therapy (Cohort B).\n- 9. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.\n- Prior/Concomitant Therapy: 13. Previous treatment with an anti-BCMA bispecific antibody.\n- Prior/Concurrent Clinical Study Experience: 14. Previous administration with an investigational drug 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).\n- Other Exclusions: 15. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.\n- 16. Known or suspected hypersensitivity to the study intervention or any of its excipients.\n- 17. Live attenuated vaccine must not be administered within 4 weeks of the first dose of study intervention.\n- 10. Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment.\n- 11. 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.\n- 12. 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/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.\n- 2. Active plasma cell leukemia.\n- 3. Amyloidosis.\n- 4. POEMS syndrome.\n- 5. Stem cell transplant within 12 weeks prior to enrollment or active GVHD.\n- 6. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment: a. Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion); b. Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); c. Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism); d. Prolonged QT syndrome (or triplicate average QTcF >470 msec at screening)."}

Primary endpoints

• {"endpoint_text":"- • ORR by BICR per IMWG.","definition_or_measurement_approach":"ORR assessed by Blinded Independent Central Review (BICR) according to International Myeloma Working Group (IMWG) criteria."}

Secondary endpoints

• {"endpoint_text":"- • ORR by BICR baseline EMD status per IMWG.","definition_or_measurement_approach":"ORR by BICR per IMWG stratified by baseline extramedullary disease status."}
• {"endpoint_text":"- • DOR by BICR and investigator per IMWG.","definition_or_measurement_approach":"Duration of response assessed by both BICR and investigator according to IMWG."}
• {"endpoint_text":"- • CRR by BICR and investigator per IMWG.","definition_or_measurement_approach":"Complete response rate assessed by BICR and investigator per IMWG."}
• {"endpoint_text":"- • ORR by investigator per IMWG.","definition_or_measurement_approach":"Overall response rate assessed by investigator per IMWG."}
• {"endpoint_text":"- • DOCR by BICR and investigator per IMWG.","definition_or_measurement_approach":"Duration of clinical response assessed by BICR and investigator per IMWG."}
• {"endpoint_text":"- • PFS by BICR and investigator per IMWG.","definition_or_measurement_approach":"Progression-free survival assessed by BICR and investigator per IMWG."}
• {"endpoint_text":"- • TTR by BICR and investigator per IMWG.","definition_or_measurement_approach":"Time to response assessed by BICR and investigator per IMWG."}
• {"endpoint_text":"- • MRD negativity rate (central lab) per IMWG.","definition_or_measurement_approach":"Minimal residual disease negativity rate measured at a central laboratory according to IMWG."}
• {"endpoint_text":"- • AEs and laboratory abnormalities as graded by NCI CTCAE v5.0.","definition_or_measurement_approach":"Adverse events and laboratory abnormalities graded using NCI CTCAE v5.0."}
• {"endpoint_text":"- • Severity of CRS and ICANS assessed according to ASTCT criteria.","definition_or_measurement_approach":"Severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) assessed per ASTCT criteria."}
• {"endpoint_text":"- • Pre- and postdose concentrations of elranatamab.","definition_or_measurement_approach":"Pharmacokinetic assessment of pre- and post-dose elranatamab concentrations."}
• {"endpoint_text":"- • ADAs and NAbs against elranatamab.","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) against elranatamab."}
• {"endpoint_text":"- • OS.","definition_or_measurement_approach":"Overall survival."}

Germany

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

05-09-2024

Processing Time Days

196

Number Of Sites

1

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

04-09-2024

Processing Time Days

195

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

06-09-2024

Processing Time Days

197

Number Of Sites

5

Number Of Participants

5

Belgium

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

09-09-2024

Processing Time Days

200

Number Of Sites

1

Number Of Participants

1

France

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

13-09-2024

Processing Time Days

204

Number Of Sites

6

Number Of Participants

17

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

Clinical operations, IMP & clinical supplies services (including storage and destruction), contracting support

Name

Calyx Medical Imaging

Responsibilities

Medical image analysis/review

Name

Labcorp Central Laboratory Services

Responsibilities

Central laboratory services

Third parties

• {"country":"United States","full_name":"Calyx Medical Imaging","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Health care"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Clinical operations and IMP & clinical supplies management; IMP & Clinical Supplies Destruction; IMP & Clinical Supplies Storage; Clinical Study Agreement Contracting Services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services","duties_or_roles":"Central Laboratory Services","organisation_type":"Health care"}