MULTIPLE MYELOMA MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PF-06863135
Product Code: PF-06863135
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Elranatamab
Current Sponsor code: PF-06863135
Concentration unit: mg/ml milligram(s
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age and Sex: 1. Male or female participants age =18 years. - A female participant is eligible to participate if she is not pregnant or breastfeeding. Within the Protocol, please refer to Appendix 4 for all reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Type of Participant and Disease Characteristics: 2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 3. Prior diagnosis of MM as defined according to IMWG criteria (Rajkumar et al, 2014). 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 (1.65) 5. Refractory to at least one IMiD. 6. Refractory to at least one PI. 7. Refractory to at least one anti-CD38 antibody. 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. 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. 10. ECOG performance status =2. 11. LVEF =40% as determined by a MUGA scan or ECHO. 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 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). 14. Adequate BM function characterized by the following: a. ANC =1.0 × 10^9/L; (use of granulocyte-colony stimulating factors is permitted if completed at least 7 days prior to planned start of dosing) b. Platelets =25 × 10^9/L; (transfusion support is permitted if completed at least 7 days prior to planned start of dosing) c. Hemoglobin =8 g/dL (transfusion support is permitted if completed at least 7 days prior to planned start of dosing). 15. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade =1 Informed Consent: 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: 1. Smoldering MM. 2. Active Plasma cell leukemia. 3. amyloidosis. 4. POEMS syndrome 5. Stem cell transplant within 12 weeks prior to enrollment or active GVHD. 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). 7. Ongoing Grade =2 peripheral sensory or motor neuropathy 8. History of any grade peripheral sensory or motor neuropathy with prior BCMA directed therapy (Cohort B) 9. History of GBS or GBS variants, or history of any Grade =3 peripheral motor polyneuropathy. 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. 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. 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. Prior/Concomitant Therapy: 13. Previous treatment with an anti-BCMA bispecific antibody. 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). 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. 16. Known or suspected hypersensitivity to the study intervention or any of its excipients. 17. Live attenuated vaccine must not be administered within 4 weeks of the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of elranatamab in patients with no prior BCMA therapy (Cohort A) and prior BCMA therapy (cohort B).;Secondary Objective: Key secondary: - To determine additional efficacy of elranatamab in Cohort A - To determine additional efficacy of elranatamab in Cohort A and Cohort B - To determine the safety and tolerability of elranatamab - To evaluate the PK of elranatamab - To evaluate the immunogenicity of elranatamab;Primary end point(s): ORR by BICR per IMWG;Timepoint(s) of evaluation of this end point: In each of Cohort A and Cohort B, BOR will be assessed based on reported overall responses recorded at evaluation time points from the date of first dose until the first documentation of PD, death or start of new anticancer therapy, whichever occurs first. - OR will encompass confirmed sCR, CR, VGPR and PR. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: - ORR by BICR baseline EMD status per IMWG To determine additional efficacy of elranatamab in Cohort A and Cohort B: - DOR by BICR and investigator per IMWG - CRR by BICR and investigator per IMWG - ORR by investigator per IMWG - DOCR by BICR and investigator per IMWG - PFS by BICR and investigator per IMWG - OS - TTR by BICR and investigator per IMWG - MRD negativity rate (central lab) per IMWG To determine the safety and tolerability of elranatamab - AEs and laboratory abnormalities as graded by NCI CTCAE v5.0. - Severity of CRS and ICANS assessed according to ASTCT criteria (Lee et al, 2019). To evaluate the PK of elranatamab - Pre- and postdose concentrations of elranatamab To evaluate the immunogenicity of elranatamab - ADAs and NAbs against elranatamab;Timepoint(s) of evaluation of this end point: Analyses of secondary efficacy endpoints will use the Safety Analysis Set. Please refer to section 9.4.3 of the protocol for a complete description of each secondary endpoint. | — |
Countries
Australia, Belgium, Canada, France, Germany, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinicalTrials.gov Call Center
Pfizer, Inc.
Outcome results
None listed