Multiple Myeloma
Conditions
Keywords
PF-06863135, Multiple Myeloma, BCMA, elranatamab, bispecific antibody, MagnetisMM-4
Brief summary
The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.
Interventions
DRUGElranatamab + Nirogacestat
BCMA-CD3 bispecific antibody + gamma secretase inhibitor
DRUGElranatamab + lenalidomide + dexamethasone
BCMA-CD3 bispecific antibody + immunomodulatory
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed/refractory multiple myeloma with at least 3 prior lines of therapy * Refractory to at least one IMiD, one proteasome inhibitor, and one anti-CD38 antibody * Measurable disease defined by at least one of the following: 1. Serum M-protein \>/= 0.5 g/dL by SPEP 2. Urinary M-protein excretion \>/= 200 mg/24 hours by UPEP 3. Serum immunoglobulin FLC \>/= 10 mg/dL (\>/= 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio * ECOG performance status 0 -1 * Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade \</= 1
Exclusion criteria
* Active plasma cell leukemia * Amyloidosis * Stem cell transplant with 12 weeks prior to enrollment, or active GVHD * POEMS syndrome * Any active uncontrolled bacterial, fungal, or viral infection * Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment * Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment (whichever is longer) * Sub-Study A Only: Previous treatment with BCMA bispecific antibody * Sub-Study B Only: Previous treatment with BCMA directed therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SSA: Number of Participants With Dose Limiting Toxicities (DLTs)- Phase 1b Dose Escalation | From Cycle 0 Day 1 through Cycle 1 Day 28 (approximately up to 35 days) | DLT- Hematological:Grade (G)4 neutropenia \>5 days; febrile neutropenia; G\>=3 neutropenia, infection; G4 thrombocytopenia; G3 thrombocytopenia and G\>=2 bleeding. Non-hematological: G\>=4 adverse events(AEs); G3 cytokine release syndrome(CRS) \[except CRS not been maximally treated or improved to G\<=1 in 48 hours\]; G3 AEs (except AEs attributed to CRS, G3 nausea, vomiting, diarrhea that improve to G2\<=72 hours after maximal medical management has been initiated, G3 fatigue \< 1 week); confirmed drug-induced liver injury meeting Hy's law criteria; G3-4 laboratory abnormalities(except not associated with clinical sequelae and improve to G=\<2 in 72 hours); G2 clinically important/persistent AEs(cause significant dose delay/reduction) may be DLT; G3 injection site reaction, allergic reaction, anaphylaxis. Common Terminology Criteria for Adverse Events(CTCAE) version 5.0: G1:mild AE, G2:moderate, G3:severe, G4:life-threatening consequences; urgent intervention indicated, G5:death related to AE. |
| SSB: Number of Participants With DLTs- Phase 1b | From Cycle 0 Day 1 through Cycle 1 Day 28 (approximately up to 42 days) | Hematological: G4 neutropenia \>5 days; febrile neutropenia; G\>=3 neutropenia with infection; G4 thrombocytopenia; G3 thrombocytopenia with G\>=2 bleeding. Non-hematological: G\>=4 AEs; G3 CRS (except CRS events: not been maximally treated or improved to grade \<=1 within 48 hours); G3 AEs (except: AEs attributed to CRS, G3 nausea, vomiting and diarrhea that improve to G2\<=72 hours after maximal medical management has been initiated, G3 fatigue \< 1 week); confirmed drug-induced liver injury meeting Hy's law criteria; G 3-4 laboratory abnormalities (except: not associated with clinical sequelae and improve to G=\<2 within 72 hours); Other clinically important/persistent AEs (that cause significant dose delay/reduction) may be DLT; G3 injection site reaction. CTCAE version 5.0: G1: Mild AE, G2: Moderate, G3: Severe, G4: Life-threatening consequences; urgent intervention indicated, G5: Death related to AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SSA: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs- Phase 1b | From treatment initiation till study completion | An adverse event was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention, including both serious and all non-serious adverse events. A serious adverse event (SAE): any untoward medical occurrence that, at any dose resulting in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. Relatedness of any AE to treatment to be judged by investigator. |
| SSA: Number of Participants With Severity of AEs According to Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Grading Criteria 2019- Phase 1b | From treatment initiation till study completion | CRS: supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T-cells and/or other immune effector cells. Symptoms must include fever at the onset, and may include hypotension, hypoxia and end organ dysfunction. As per ASTCT criteria, G1: fever (temperature \>=38 degree Celsius), hypotension and/or hypoxia none; G2: fever, hypotension not requiring vasopressors, hypoxia requiring low-flow nasal cannula/facemask or blow-by; G3: fever, hypotension requiring a vasopressor with or without vasopressin, hypoxia requiring high-flow nasal cannula/facemask, nonrebreather mask, or Venturi mask; G4: fever, hypotension requiring multiple vasopressors (excluding vasopressin), hypoxia requiring positive pressure. Organ toxicities associated with CRS graded according to CTCAE v5.0. G1: mild, G2: moderate, G3: severe, G4: life-threatening consequences; urgent intervention indicated. G5: death related to AE. |
| SSA: Number of Participants With Severity of AEs According to Immune Effector Cell-associated Neurotoxicity Syndrome ICANS Graded According to ASTCT Grading Criteria 2019- Phase 1b | From treatment initiation till study completion | ASTCT for ICANS \[immune effector cell-associated encephalopathy (ICE, overall score range 0-10, higher score = better condition). G1: ICE score 7-9, awakens spontaneously; G2: ICE score 3-6, awakens to voice; G3: ICE score 0-2, awakens only to tactile stimulus, any clinical seizure that resolves rapidly or non-convulsive seizures on electroencephalography that resolve with intervention, focal/local oedema on neuroimaging; G4: ICE score 0 (unarousable and unable to perform ICE), unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma, life-threatening prolonged seizure (\>5 min); or repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness such as hemiparesis or paraparesis, diffuse cerebral oedema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI (abducens nerve) palsy; or papilledema; or Cushing's triad; G5: death. |
| SSA: Number of Participants With Laboratory Abnormalities- Phase 1b | From treatment initiation till study completion | Number of participants with laboratory abnormalities will be reported in this outcome measure. |
| SSA: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria as Determined by Investigator- Phase 1b | From treatment initiation till study completion | ORR: % of participants with objective response. Stringent complete response(sCR): CR \& normal serum free light chain (sFLC) ratio \&absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum \&urine, disappearance of soft tissue plasmacytomas \&\<5% plasma cells in BMA. If disease measurable by sFLC only, preceding criteria \&normal sFLC ratio. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum M-protein \& urine M-protein level \<100 mg/24h; PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M-protein by \>=90% or to \<200 mg/24 hours (If disease measurable by sFLC only: VGPR \& PR: \>=90% \&\>=50% decrease in difference respectively between involved \& uninvolved sFLC levels). In addition, if present at baseline, VGPR \& PR: \>=90% \&\>=50% reduction compared with baseline in soft tissue plasmacytomas' size. |
| SSA: Complete Response Rate (CRR) as Per IMWG Criteria as Determined by Investigator- Phase 1b | From treatment initiation till study completion | CRR was defined as the percentage of participants with a Best Overall Response (BOR) of confirmed sCR/CR per IMWG response criteria as determined by investigator. sCR: i) CR; ii) normal serum FLC ratio and absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence (κ/λ ratio \<=4:1 or \>=1:2 for κ and λ participants, respectively, after counting \>=100 plasma cells; iii) if the only measurable disease was by serum FLC levels, sCR was defined as normal serum FLC ratio of 0.26 to 1.65 plus absence of clonal cells in BMB/BMA b by immunohistochemistry or immunofluorescence (κ/λ ratio \<=4:1 or \>=1:2 for κ and λ participants, respectively, after counting \>=100 plasma cells). CR: i) negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BMA; ii) if the only measurable disease was by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65 plus criteria (i). |
| SSA: Time to Response (TTR) as Per IMWG Criteria as Determined by Investigator-Phase 1b | From treatment initiation till study completion | TTR was defined, for participants with an objective response per IMWG criteria, as the time from the date of first dose to the first documentation of objective response that is subsequently confirmed. |
| SSA: Duration of Response (DOR) as Per IMWG Criteria as Determined by Investigator- Phase 1b | From treatment initiation till study completion | DOR (for participants (pts) with objective response (OR) per IMWG)=time from the first OR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) \>=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc \>=0.5 g/dL) (b)Serum M-protein inc \>=1 g/dL if lowest M component \>=5 g/dL (c)Urine M-protein (abs inc \>=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc \>10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc \>=10%) (ii)appearance of new lesion(s), \>=50% inc from nadir in SPD of \>1 lesion, or \>= 50% inc in longest diameter of a prior lesion \>1 cm in short axis (iii)\>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease. |
| SSA: Duration of Complete Response (DOCR) as Per IMWG Criteria as Determined by Investigator- Phase 1b | From treatment initiation till study completion | DOCR (for participants (pts) with CR/sCR per IMWG)= time from the first CR/sCR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) \>=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc \>=0.5 g/dL) (b)Serum M-protein inc \>=1 g/dL if lowest M component \>=5 g/dL (c)Urine M-protein (abs inc \>=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc \>10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc \>=10%) (ii)appearance of new lesion(s), \>=50% inc from nadir in SPD of \>1 lesion, or \>= 50% inc in longest diameter of a prior lesion \>1 cm in short axis (iii)\>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease. |
| SSA: Progression Free Survival (PFS) as Per IMWG Criteria as Determined by Investigator- Phase 1b | From treatment initiation till study completion | PFS=time from date of first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) \>=25% from lowest confirmed response value of (a)Serum M-component (absolute (abs) inc \>=0.5 g/dL) (b)Serum M-protein inc \>=1 g/dL if lowest M component \>=5 g/dL (c)Urine M-protein (abs inc \>=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc \>10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc \>=10%) (ii)appearance of new lesion(s), \>=50% inc from nadir in SPD of \>1 lesion, or \>= 50% inc in longest diameter of a previous lesion \>1 cm in short axis (iii)\>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease. |
| SSA: Overall Survival (OS)- Phase 1b | From treatment initiation till study completion | OS was defined as the time from the first date of the study intervention to the date of death due to any cause. Participants not known to have died are censored on the date of last known alive. |
| SSA: Minimal Residual Disease (MRD) Negativity Rate as Per IMWG Criteria- Phase 1b | From treatment initiation till study completion | MRD negativity rate is defined as the proportion of participants with CR or better by investigator and negative MRD (assessed by central lab) per IMWG sequencing criteria at any time from the date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurs first. 1) CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BMA. If the only measurable disease is by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65; 2) Sequencing MRD-negative: Absence of clonal plasma cells by next generation sequencing (NGS) on BMA in which presence of a clone was defined as \<2 identical sequencing reads obtained after DNA sequencing of BMA using the LymphoSIGHT platform (or validated equivalent method) with a minimum sensitivity of 1 in 10\^5 nucleated cells. |
| SSA: Pre- and Post-dose Concentrations of Elranatamab- Phase 1b | From treatment initiation till study completion | — |
| SSA: Trough Serum Concentrations of Nirogacestat- Phase 1b | From treatment initiation till study completion | — |
| SSA: Number of Participants With Anti-drug Antibodies (ADA)- Phase 1b | From treatment initiation till study completion | — |
| SSA: Number of Participants With Neutralizing Antibodies (NAb)- Phase 1b | From treatment initiation till study completion | — |
| SSB: Number of Participants With TEAEs and Treatment Related TEAEs- Phase 1b | From treatment initiation till study completion | AE: any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention, including both serious and all non-serious adverse events. A SAE: any untoward medical occurrence that, at any dose resulting in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. Relatedness of any AE to treatment to be judged by investigator. |
| SSB: Number of Participants With Severity of Adverse Events According to CRS Graded According to ASTCT Grading Criteria 2019- Phase 1b Dose Escalation | From treatment initiation till study completion | CRS: supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T-cells and/or other immune effector cells. Symptoms must include fever at the onset, and may include hypotension, hypoxia and end organ dysfunction. As per ASTCT criteria, G1: fever (temperature \>=38 degree Celsius), hypotension and/or hypoxia none; G2: fever, hypotension not requiring vasopressors, hypoxia requiring low-flow nasal cannula/facemask or blow-by; G3: fever, hypotension requiring a vasopressor with or without vasopressin, hypoxia requiring high-flow nasal cannula/facemask, nonrebreather mask, or Venturi mask; G4: fever, hypotension requiring multiple vasopressors (excluding vasopressin), hypoxia requiring positive pressure. Organ toxicities associated with CRS graded according to CTCAE v5.0. G1: mild, G2: moderate, G3: severe, G4: life-threatening consequences; urgent intervention indicated. G5: death related to AE. |
| SSB: Number of Participants With Severity of Adverse Events According to ICANS Graded According to ASTCT Grading Criteria 2019- Phase 1b Dose Escalation | From treatment initiation till study completion | ASTCT for ICANS (ICE, overall score range 0-10, higher score = better condition). G1: ICE score 7-9, awakens spontaneously; G2: ICE score 3-6, awakens to voice; G3: ICE score 0-2, awakens only to tactile stimulus, any clinical seizure that resolves rapidly or non-convulsive seizures on electroencephalography that resolve with intervention, focal/local oedema on neuroimaging; G4: ICE score 0 (unarousable and unable to perform ICE), unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma, life-threatening prolonged seizure (\>5 min); or repetitive clinical or electrical seizures without return to baseline in between, deep focal motor weakness such as hemiparesis or paraparesis, diffuse cerebral oedema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI (abducens nerve) palsy; or papilledema; or Cushing's triad; G5: death. |
| SSB: Number of Participants With Laboratory Abnormalities- Phase 1b Dose Escalation | From treatment initiation till study completion | Number of participants with laboratory abnormalities will be reported in this outcome measure. |
| SSB: ORR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation | From treatment initiation till study completion | ORR: % of participants with objective response. sCR: CR \& normal sFLC ratio and absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas \&\<5% plasma cells in BMA. If disease measurable by sFLC only, preceding criteria \&normal sFLC ratio. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum M-protein \& urine M-protein level \<100 mg/24h; PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M-protein by \>=90% or to \<200 mg/24 hours (If disease measurable by sFLC only: VGPR \& PR: \>=90% \&\>=50% decrease in difference respectively between involved \& uninvolved sFLC levels). In addition, if present at baseline, VGPR \& PR: \>=90% \&\>=50% reduction compared with baseline in soft tissue plasmacytomas' size. |
| SSB: CRR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation | From treatment initiation till study completion | CRR was defined as the percentage of participants with a BOR of confirmed sCR/CR per IMWG response criteria as determined by investigator. sCR: i) CR; ii) normal serum FLC ratio and absence of clonal cells in BMB/BMA by immunohistochemistry or immunofluorescence (κ/λ ratio \<=4:1 or \>=1:2 for κ and λ participants, respectively, after counting \>=100 plasma cells; iii) if the only measurable disease was by serum FLC levels, sCR was defined as normal serum FLC ratio of 0.26 to 1.65 plus absence of clonal cells in BMB/BMA b by immunohistochemistry or immunofluorescence (κ/λ ratio \<=4:1 or \>=1:2 for κ and λ participants, respectively, after counting \>=100 plasma cells). CR: i) negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BMA; ii) if the only measurable disease was by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65 plus criteria (i). |
| SSB: TTR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation | From treatment initiation till study completion | TTR was defined for participants with an objective response per IMWG criteria, as the time from the date of first dose to the first documentation of objective response that is subsequently confirmed. |
| SSB: DOR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation | From treatment initiation till study completion | DOR (for participants (pts) with objective response (OR) per IMWG)=time from the first OR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) \>=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc \>=0.5 g/dL) (b)Serum M-protein inc \>=1 g/dL if lowest M component \>=5 g/dL (c)Urine M-protein (abs inc \>=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc \>10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc \>=10%) (ii)appearance of new lesion(s), \>=50% inc from nadir in SPD of \>1 lesion, or \>= 50% inc in longest diameter of a prior lesion \>1 cm in short axis (iii)\>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease. |
| SSB: DOCR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation | From treatment initiation till study completion | DOCR (for participants (pts) with CR/sCR per IMWG)= time from the first CR/sCR that is confirmed (conf), until conf PD per IMWG, or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) \>=25% from lowest conf response value of (a)Serum M-component (absolute (abs) inc \>=0.5 g/dL) (b)Serum M-protein inc \>=1 g/dL if lowest M component \>=5 g/dL (c)Urine M-protein (abs inc \>=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc \>10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc \>=10%) (ii)appearance of new lesion(s), \>=50% inc from nadir in SPD of \>1 lesion, or \>= 50% inc in longest diameter of a prior lesion \>1 cm in short axis (iii)\>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease. |
| SSB: PFS as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation | From treatment initiation till study completion | PFS=time from date of first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. PD=any of: (i)Increase (inc) \>=25% from lowest confirmed response value of (a)Serum M-component (absolute (abs) inc \>=0.5 g/dL) (b)Serum M-protein inc \>=1 g/dL if lowest M component \>=5 g/dL (c)Urine M-protein (abs inc \>=200 mg/24 h) (d)in pts without measurable (meas) serum and urine M-protein levels, difference between involved and uninvolved serum FLC levels (abs inc \>10 mg/dL) (e)in pts without meas serum and urine M-protein levels and without meas involved serum FLC, bone marrow plasma-cell (PC) percentage irrespective of baseline status (abs inc \>=10%) (ii)appearance of new lesion(s), \>=50% inc from nadir in SPD of \>1 lesion, or \>= 50% inc in longest diameter of a previous lesion \>1 cm in short axis (iii)\>=50% inc in circulating PC (minimum 200 cells per microliter) if the only measure of disease. |
| SSB: OS- Phase 1b Dose Escalation | From treatment initiation till study completion | OS was defined as the time from the first date of the study intervention to the date of death due to any cause. Participants not known to have died are censored on the date of last known alive. |
| SSB: MRD Negativity Rate as Per IMWG Criteria- Phase 1b Dose Escalation | From treatment initiation till study completion | MRD negativity rate is defined as the proportion of participants with CR or better by investigator and negative MRD (assessed by central lab) per IMWG sequencing criteria at any time from the date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurs first. 1) CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in BMA. If the only measurable disease is by serum FLC levels, CR was defined as normal serum FLC ratio of 0.26 to 1.65; 2) Sequencing MRD-negative: Absence of clonal plasma cells by next generation sequencing (NGS) on BMA in which presence of a clone was defined as \<2 identical sequencing reads obtained after DNA sequencing of BMA using the LymphoSIGHT platform (or validated equivalent method) with a minimum sensitivity of 1 in 10\^5 nucleated cells. |
| SSB: Pre- and Post-dose Concentrations of Elranatamab- Phase 1b Dose Escalation | From treatment initiation till study completion | — |
| SSB: Trough Serum Concentrations of Lenalidomide- Phase 1b Dose Escalation | From treatment initiation till study completion | — |
| SSA: Number of Participants With ADA- Phase 1b Dose Escalation | From treatment initiation till study completion | — |
| SSB: Number of Participants With NAb- Phase 1b Dose Escalation | From treatment initiation till study completion | — |
Countries
Canada, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
A total of 46 participants were enrolled in this study. Study had two sub-studies: sub-study A (SSA) and sub-study B (SSB). Phase 1b and Phase 2 were planned for SSA, while Phase 1b for SSB. Phase 2 of SSA was not conducted, based on sponsor's decision. Hence there is no data reported for Phase 2 in any section of the results' record.
Pre-assignment details
Outcome measures data are reported at Primary Completion Date, and data is disclosed for only those outcome measures whose analysis were final. Remaining outcome measures' data would be reported upon their complete analyses at study completion date. Safety summaries reported are until October 2025 (approximately up to 48 months).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.74 Years STANDARD_DEVIATION 9.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 3 / 6 | 3 / 10 | 2 / 10 | 1 / 6 | 5 / 12 | 15 / 46 |
| other Total, other adverse events | 2 / 2 | 6 / 6 | 10 / 10 | 10 / 10 | 6 / 6 | 11 / 12 | 45 / 46 |
| serious Total, serious adverse events | 1 / 2 | 5 / 6 | 6 / 10 | 6 / 10 | 4 / 6 | 7 / 12 | 29 / 46 |
Outcome results
None listed