PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Drug: PF-06863135 monotherapy IV or SC
- Registration Number
- NCT03269136
- Lead Sponsor
- Pfizer
- Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
- Detailed Description
Study C1071001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 in adult patients with advanced multiple myeloma who have relapsed from or are refractory to standard therapy. This is a two part study; Part 1 will assess the safety and tolerability of increasing dose levels of PF-06863135 and Part 2 will evaluate safety and anti-myeloma activity of PF-06863135 at the RP2Ds determined in Part 1.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- Relapsed/refractory multiple myeloma
- Progressed or are intolerant of established therapies including proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody
- Performance Status of 0- 1 ( Performance Score 2 is permitted only if due to underlying myeloma)
- Adequate bone marrow, hematological, kidney and liver function
- Resolved acute effects of any prior therapy to baseline severity
- Not pregnant
- Recent history of other malignancies
- History of active autoimmune disorders
- Any form of primary immunodeficiency
- Active and clinically significant bacterial, fungal, or viral infection
- Evidence of active mucosal or internal bleeding
- History of severe immune-mediated adverse event with prior immunomodulatory treatment
- Major surgery within 4 weeks of study treatment start
- Radiation therapy within 2 weeks of study treatment start
- History of stem cell transplant (autologous or allogeneic) within 100 days prior to study enrollment
- Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry
- Less than 30 days since last dose of antibody based therapies or less than 5 half-lives since last dose of previous therapy
- Requirement for systemic immune suppressive medication except as permitted in the protocol
- Current requirement for chronic blood product support
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PF-06863135 + pomalidomide PF-06863135 + pomalidomide BCMA-CD3 bispecific antibody + pomalidomide PF-06863135 PF-06863135 monotherapy IV or SC BCMA-CD3 bispecific antibody PF-06863135 + dexamethasone PF-06863135 + dexamethasone BCMA-CD3 bispecific antibody + dexamethasone PF-06863135 + lenalidomide PF-06863135 + lenalidomide BCMA-CD3 bispecific antibody + lenalidomide
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Drug Limiting Toxicities (DLTs) Graded According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v)4.03 Cycle 1 (21 Days) Hematological: Grade 4 neutropenia lasting \>5 days; Febrile neutropenia \<1000/mm\^3 with a single temperature of \>38.3 degree Celsius (C) or a sustained temperature of \>=38 degree C for more than one hour; grade \>=3 neutropenia with infection; grade 4 thrombocytopenia; grade 3 thrombocytopenia with \>= Grade 2 bleeding. Non-hematological: grade 4 adverse events (AEs); Grade 3 AE lasting \>=5 days despite optimal supportive care, with exception of AE attributed to cytokine release syndrome (CRS) event; grade 3 CRS, except those CRS that had a) not been maximally treated or b) improved to \<=grade 1 within 48 hours; grade 4 CRS; confirmed drug-induced liver injury (DILI) meeting Hy's law criteria; grade 4 laboratory abnormalities deemed clinically significant by the investigator reported Grade 4 AE; clinically important or persistent toxicities that were not included in above criteria were also be considered a DLT following review by the investigators and the sponsor.
Part 2: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months) ORR per IMWG criteria: percentage of participants with best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). sCR: complete response plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hr. PR: \>=50% reduction of serum M-protein and reduction in 24 hrs urinary M-protein by \>=90% or to \<200 mg/24 hr. If serum and urine M-protein were unmeasurable, \>=50% decrease in difference between involved and uninvolved FLC levels required in place of the M-protein criteria.
Part 2: Duration of Response (DOR) as Per IMWG Criteria From the first documentation of objective tumor response to first documentation of objective tumor progression or new anti-cancer therapies or death, whichever occurred first, (maximum up to 34.3 months) DOR per IMWG criteria:time from first documentation of objective tumor (OT)response to first documentation of OTprogression or to death due to any cause, whichever occurred first.sCR: CR plus normal FLC ratio \& absence of clonal cells in bone marrow biopsy by immunohistochemistry;CR:Negative immunofixation on serum \& urine \& disappearance of any soft tissue plasmacytomas\&\<5% plasma cells in bone marrow aspirates.VGPR: serum \& urine M-protein(Mp) detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum Mp plus urine Mp level \<100 mg/24 hr. PR: \>=50% reduction of serum Mp \& reduction in 24 hrs urinary Mp by \>=90% or to \<200 mg/24 hr.If serum \& urine Mp were unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of Mp criteria. Progression: appearance of local, regional or distant disease of same type after CR or progression of pre-existing lesions. It did not include second primary malignancies of unrelated types.
- Secondary Outcome Measures
Name Time Method Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs), Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03 From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months) AE: any untoward medical occurrence in clinical study participant, temporally associated with use of study intervention, whether or not considered related to intervention. TEAE: any event increasing in severity from baseline or event started during PF-06863135 therapy or within 30 days of last dose of drug. SAE: any untoward medical occurrence at any dose that resulted in either: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission via Pfizer product of infectious agent, pathogenic or non-pathogenic; or considered as important event. Treatment-related AE: AEs attributed to drug in participants who received drug. Relatedness was judged by investigator. NCI CTCAE v4.03, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. AEs included SAEs and all non-SAEs.
Part 1: Number of Participants With Shifts From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months) Hematology parameters included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and, white blood cell decreased. According to NCI CTCAE version 4.03: Grade 1= mild, Gade 2= moderate, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. In this outcome measure number of participants with shifts from grade 2 at baseline to grade 3 or 4 post-baseline in any of hematology parameters are reported.
Part 1: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months) Clinical chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia and hypophosphatemia. According to NCI CTCAE version 4.03: Grade 1= mild, Gade 2= moderate, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. In this outcome measure number of participants with shifts from grade 2 at baseline to grade 3 or 4 post-baseline in any of clinical chemistry parameters are reported.
Part 1: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Urinalysis From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months) Proteinuria was estimated in urinalysis. According to NCI CTCAE version 4.03: Grade 1= mild, Gade 2= moderate, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. In this outcome measure number of participants with shifts from grade 2 at baseline to grade 3 or 4 post-baseline in any of urinalysis parameters are reported.
Part 1: ORR as Per IMWG Criteria From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months) ORR per IMWG criteria: percentage of participants with best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). sCR: complete response plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hr. PR: \>=50% reduction of serum M-protein and reduction in 24 hrs urinary M-protein by \>=90% or to \<200 mg/24 hr. If serum and urine M-protein were unmeasurable, \>=50% decrease in difference between involved and uninvolved FLC levels required in place of the M-protein criteria.
Part 1: Time to Response (TTR) as Per IMWG Criteria From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months) TTR: Defined for participants with confirmed objective response as time from first dose to first documentation of objective tumor response. sCR: complete response + normal FLC ratio \& absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: Negative immunofixation on serum\& urine \& disappearance of soft tissue plasmacytomas \& \<5% plasma cells in bone marrow aspirates. VGPR: serum\& urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hr. PR: \>=50% reduction of serum M-protein\& reduction in 24hrs urinary M-protein by \>=90% or \<200 mg/24hr. If serum \& urine M-protein unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of M-protein criteria. Progression: Appearance of local, regional, distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types.
Part 1: Complete Response Rate (CRR) as Per IMWG Criteria From the first dose of study treatment until the first documented sCR or CR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months) CRR: percentage of participants with complete response (sCR or CR). sCR: complete response plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates.
Part 1: DOR as Per IMWG Criteria From the first documentation of objective tumor response to first documentation of objective tumor progression or new anti-cancer therapies or death, whichever occurred first, (maximum up to 63.31 months) DOR per IMWG criteria:time from first documentation of objective tumor (OT)response to first documentation of OTprogression or to death due to any cause, whichever occurred first.sCR: CR plus normal FLC ratio \& absence of clonal cells in bone marrow biopsy by immunohistochemistry;CR:Negative immunofixation on serum \& urine \& disappearance of any soft tissue plasmacytomas\&\<5% plasma cells in bone marrow aspirates.VGPR: serum \& urine M-protein(Mp) detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum Mp plus urine Mp level \<100 mg/24 hr. PR: \>=50% reduction of serum Mp \& reduction in 24 hrs urinary Mp by \>=90% or to \<200 mg/24 hr.If serum \& urine Mp were unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of Mp criteria. Progression: appearance of local, regional or distant disease of same type after CR or progression of pre-existing lesions. It did not include second primary malignancies of unrelated types.
Part 1: Duration of Complete Response (DoCR) as Per IMWG Criteria From the first documentation of complete response to the first documentation of tumor progression or death, whichever occurred first (maximum up to 63.31 months) DoCR was defined for participants with confirmed complete response (sCR or CR) as the time from the first documentation of complete response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. sCR: complete response plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Progression was defined as appearance of local, regional or distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types.
Part 1: Duration of Stable Disease (DOSD) as Per IMWG Criteria Time from the first documentation of objective stable disease to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 63.31 months) DOSD per IMWG criteria: participants with confirmed stable disease (SD): time from first documentation (doc) of objective SD to first doc of objective tumor progression (P)/death by any cause, whichever occurred first. SD: not meeting criteria for CR,VGPR, PR, MR or PD. CR: Negative immunofixation on serum \& urine \&disappearance of any soft tissue plasmacytomas \&\<5% plasma cells in bone marrow aspirates. VGPR: serum \& urine M-protein (Mp) detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum Mp plus urine Mp level \<100 mg/24 hr. PR: \>=50% reduction of serum Mp \& reduction in 24 hours urinary Mp by \>=90% or\<200 mg/24 hr. If serum \& urine Mp were unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of Mp criteria. Progression: appearance of local, regional, distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types.
Part 1: Progression Free Survival (PFS) as Per IMWG Criteria From start date of study treatment to date of first documentation of progression or death due to any cause, whichever occurred first (maximum up to 63.31 months) PFS as per IMWG criteria was the time from start date of study treatment to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after CR or progression of pre-existing lesions. It does not include second primary malignancies of unrelated types. CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates.
Part 1: Overall Survival (OS) Time from start date of study treatment to date of death due to any cause or last-known-alive date, whichever occurred first (maximum up to 63.31 months) OS was defined as the time from start date of study treatment to date of death due to any cause. OS for participants not known to had died were censored on the date of last known alive.
Part 1: Percentage of Participants With Negative Minimal Residual Disease (MRD) Using IMWG MRD Criteria Anytime from date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurred first (maximum up to 63.31 months) MRD negativity rate: percentage of participants with negative MRD (assessed by central laboratory) per IMWG criteria at any time from date of first dose until first documentation of confirmed progression, death or start of new anticancer therapy, whichever occurred first. Progression was defined as appearance of local, regional, distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types. MRD negativity was defined by two thresholds, 10\^-5 and 10\^-6.
Part 1: Maximum Observed Concentration (Cmax) of PF-06863135 0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2 Cmax of PF-06863135 was measured in this outcome measure. Total is free and bound drug in the body.
Part 1: Area Under the Concentration-Time Profile From Time 0 to End of Dosing Interval (AUCtau) 0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2 Area under the concentration curve from time 0 to end of dosing interval (AUCtau) was measured in this outcome measure. Total is free and bound drug in the body.
Part 1C and Part 1D: Plasma Concentration of Lenalidomide and Pomalidomide Cycle 1 (0 hours post dose on Day 1, 8 and 15); Cycle 2 (0 hours on Day 15) Plasma concentration of lenalidomide and pomalidomide was measured in this outcome measure.
Part 1: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06863135 From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 63.31 months) Number of participants with ADA and NAb against PF-06863135 were reported in this outcome measure. A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participant had \>= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \>= 4-folder dilution increase in titer from baseline in \>= 1 post-treatment sample (treatment-boosted).
Part 1: Concentration of Soluble Cytokines in Serum Part 1: C1 (0, 2, 4 & 8 hours [h] post dose on Day [D] 1, 24h post dose on D2, 72h post dose on D3); Part 1.1, 1C & 1D: C0 (0, 2, 4 & 8h post dose on D1, 24h post dose on D2); C1 (0, 2, 4 & 8h post dose on D1, 24h post dose on D2, 72h post dose on D3) The concentration of Interleukin-2, Interleukin-6, Interferon-gamma and tumor necrosis factor-alpha were measured in this outcome measure. Cycle = C.
Part 2: Number of Participants With AEs, Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03 From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months) AE: any untoward medical occurrence in clinical study participant, temporally associated with use of study intervention, whether or not considered related to intervention. TEAE: any event increasing in severity from baseline or event started during PF-06863135 therapy or within 30 days of last dose of drug. SAE: any untoward medical occurrence at any dose that resulted in either: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission via Pfizer product of infectious agent, pathogenic or non-pathogenic; or considered as important event. Treatment-related AE: AEs attributed to drug in participants who received drug. Relatedness was judged by investigator. NCI CTCAE v4.03, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. AEs included SAEs and all non-SAEs.
Part 2: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months) Hematology parameters included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and, white blood cell decreased. According to NCI CTCAE version 4.03: Grade 1= mild, Gade 2= moderate, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. In this outcome measure number of participants with shifts from grade 2 at baseline to grade 3 or 4 post-baseline in any of hematology parameters are reported.
Part 2: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months) Clinical chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia and hypophosphatemia. According to NCI CTCAE version 4.03: Grade 1= mild, Gade 2= moderate, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. In this outcome measure number of participants with shifts from grade 2 at baseline to grade 3 or 4 post-baseline in any of clinical chemistry parameters are reported.
Part 2: Number of Participants With Shifts From Grade <=2 to Grade 3 or 4 Post-Baseline in Urinalysis From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months) Proteinuria was estimated in urinalysis. According to NCI CTCAE version 4.03: Grade 1= mild, Gade 2= moderate, Grade 3= severe AE, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE. In this outcome measure number of participants with shifts from grade 2 at baseline to grade 3 or 4 post-baseline in any of urinalysis parameters are reported.
Part 2: CRR as Per IMWG Criteria From the first dose of study treatment until the first documented sCR or CR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months) CRR: percentage of participants with complete response (sCR or CR). sCR: complete response plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates.
Part 2: DoCR as Per IMWG Criteria From the first documentation of complete response to the first documentation of tumor progression or death, whichever occurred first (maximum up to 34.3 months) DoCR was defined for participants with confirmed complete response (sCR or CR) as the time from the first documentation of complete response to the first documentation of objective tumor progression or to death due to any cause, whichever occured first. sCR: complete response plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Progression was defined as appearance of local, regional or distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types.
Part 2: TTR as Per IMWG Criteria From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months) TTR: Defined for participants with confirmed objective response as time from first dose to first documentation of objective tumor response. sCR: complete response + normal FLC ratio \& absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: Negative immunofixation on serum\& urine \& disappearance of soft tissue plasmacytomas \& \<5% plasma cells in bone marrow aspirates. VGPR: serum\& urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hr. PR: \>=50% reduction of serum M-protein\& reduction in 24hrs urinary M-protein by \>=90% or \<200 mg/24hr. If serum \& urine M-protein unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of M-protein criteria. Progression: Appearance of local, regional, distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types.
Part 2: DOSD as Per IMWG Criteria Time from the first documentation of objective stable disease to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 34.3 months) DOSD per IMWG criteria: participants with confirmed stable disease (SD): time from first documentation (doc) of objective SD to first doc of objective tumor progression (P)/death by any cause, whichever occurred first. SD: not meeting criteria for CR,VGPR, PR, MR or PD. CR: Negative immunofixation on serum \& urine \&disappearance of any soft tissue plasmacytomas \&\<5% plasma cells in bone marrow aspirates. VGPR: serum \& urine M-protein (Mp) detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum Mp plus urine Mp level \<100 mg/24 hr. PR: \>=50% reduction of serum Mp \& reduction in 24 hours urinary Mp by \>=90% or\<200 mg/24 hr. If serum \& urine Mp were unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of Mp criteria. Progression: appearance of local, regional, distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types.
Part 2: PFS as Per IMWG Criteria From start date of study treatment to date of first documentation of progression or death due to any cause, whichever occurred first (maximum up to 34.3 months) PFS as per IMWG criteria was the time from start date of study treatment to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after CR or progression of pre-existing lesions. It does not include second primary malignancies of unrelated types. CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates.
Part 2: OS Time from start date of study treatment to date of death due to any cause or last-known-alive date, whichever occurred first (maximum up to 34.3 months) OS was defined as the time from start date of study treatment to date of death due to any cause. OS for participants not known to had died were censored on the date of last known alive.
Part 2: Percentage of Participants With Negative MRD After Treatment With PF-06863135 Using IMWG MRD Criteria Anytime from date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy whichever occurred first (maximum up to 34.3 months) MRD negativity rate: percentage of participants with negative MRD (assessed by central laboratory) per IMWG criteria at any time from date of first dose until first documentation of confirmed progression, death or start of new anticancer therapy, whichever occurred first. Progression was defined as appearance of local, regional, distant disease of same type after CR or progression of pre-existing lesions. It didn't include second primary malignancies of unrelated types. MRD negativity was defined by two thresholds, 10\^-5 and 10\^-6.
Part 2: Number of Participants With ADA and NAb Against PF-06863135 From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 34.3 months) Number of participants with ADA and NAb against PF-06863135 were reported in this outcome measure. A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participant had \>= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \>= 4-folder dilution increase in titer from baseline in \>= 1 post-treatment sample (treatment-boosted).
Part 2: Concentration of Soluble Cytokines in Serum Cycle 0 (0, 2, 4 and 8 hours post dose on Day 1, 24 hours post dose on Day 2); Cycle 1 (0, 2, 4 and 8 hours post dose on Day 1, 24 hours post dose on Day 2, 72 hours post dose on Day 3) The concentration of Interleukin-2, Interleukin-6, Interferon-gamma and tumor necrosis factor-alpha were measured in this outcome measure.
Trial Locations
- Locations (37)
UChicago Medicine - River East
🇺🇸Chicago, Illinois, United States
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)
🇺🇸La Jolla, California, United States
UCSD Medical Center - Vista
🇺🇸Vista, California, United States
UCSD Medical Center - Encinitas
🇺🇸Encinitas, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
UChicago Medicine at Ingalls - Flossmoor
🇺🇸Flossmoor, Illinois, United States
UChicago Medicine Ingalls Memorial
🇺🇸Harvey, Illinois, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
The University of Chicago Medicine Center for Advanced Care Orland Park
🇺🇸Orland Park, Illinois, United States
UChicago Medicine at Ingalls - Tinley Park
🇺🇸Tinley Park, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
UC San Diego Medical Center - Hillcrest
🇺🇸San Diego, California, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center at Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center at Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center at Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering Cancer Center at Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center at Westchester
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center at Nassau
🇺🇸Uniondale, New York, United States
Duke University Health System: Adult Bone Marrow Transplant Clinic
🇺🇸Durham, North Carolina, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Henry Joyce Cancer Center
🇺🇸Nashville, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Investigational Drug Services, Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Unit 57, Special Services Building
🇨🇦Calgary, Alberta, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
University Health Network - Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
MUHC, GLEN site
🇨🇦Montreal, Quebec, Canada