PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma

Browse trials for

• Multiple Myeloma 3,627
• Neoplasms, Plasma Cell 2,308

Keywords

• Multiple Myeloma
• relapse/ refractory multiple myeloma
• bispecific antibody
• bispecific
• BCMA
• BCMA- CD3 bispecific
• Phase 1
• PF-06863135
• dexamethasone
• lenalidomide
• pomalidomide

Study arms

• Experimental
  PF-06863135

  BCMA-CD3 bispecific antibody

  Drug: PF-06863135 monotherapy IV or SC

• Experimental
  PF-06863135 + dexamethasone

  BCMA-CD3 bispecific antibody + dexamethasone

  Drug: PF-06863135 + dexamethasone

• Experimental
  PF-06863135 + lenalidomide

  BCMA-CD3 bispecific antibody + lenalidomide

  Drug: PF-06863135 + lenalidomide

• Experimental
  PF-06863135 + pomalidomide

  BCMA-CD3 bispecific antibody + pomalidomide

  Drug: PF-06863135 + pomalidomide

Interventions

• DrugPF-06863135 monotherapy IV or SC

  PF-06863135 will be administered intravenously or subcutaneously.

  Also known as: BCMA-CD3 bispecific antibody

• DrugPF-06863135 + dexamethasone

  PF-06863135 will be administered intravenously or subcutaneously and dexamethasone orally.

  Also known as: BCMA-CD3 bispecific antibody + dexamethasone

• DrugPF-06863135 + lenalidomide

  PF-06863135 will be administered intravenously or subcutaneously and lenalidomide orally

  Also known as: BCMA-CD3 bispecific antibody + lenalidomide

• DrugPF-06863135 + pomalidomide

  PF-06863135 will be administered intravenously or subcutaneously and pomalidomide orally

  Also known as: BCMA-CD3 bispecific antibody + pomalidomide

Primary outcomes

1. 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

   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.

   Time frame: Cycle 1 (21 Days)

2. Part 2: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria

   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.

   Time frame: 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)

3. Part 2: Duration of Response (DOR) as Per IMWG Criteria

   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.

   Time frame: 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)

Secondary outcomes

1. 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

   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.

   Time frame: 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)

2. 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

   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.

   Time frame: 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)

3. Part 1: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters

   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.

   Time frame: 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)

4. Part 1: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Urinalysis

   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.

   Time frame: 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)

5. Part 1: ORR as Per IMWG Criteria

   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.

   Time frame: 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)

6. Part 1: Time to Response (TTR) as Per IMWG Criteria

   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.

   Time frame: 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)

7. Part 1: Complete Response Rate (CRR) as Per IMWG Criteria

   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.

   Time frame: 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)

8. Part 1: DOR as Per IMWG Criteria

   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.

   Time frame: 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)

9. Part 1: Duration of Complete Response (DoCR) as Per IMWG Criteria

   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.

   Time frame: 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)

10. Part 1: Duration of Stable Disease (DOSD) as Per IMWG Criteria

    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.

    Time frame: 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)

11. Part 1: Progression Free Survival (PFS) as Per IMWG Criteria

    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.

    Time frame: 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)

12. Part 1: Overall Survival (OS)

    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.

    Time frame: 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)

13. Part 1: Percentage of Participants With Negative Minimal Residual Disease (MRD) Using IMWG MRD Criteria

    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.

    Time frame: 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)

14. Part 1: Maximum Observed Concentration (Cmax) of PF-06863135

    Cmax of PF-06863135 was measured in this outcome measure. Total is free and bound drug in the body.

    Time frame: 0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2

15. Part 1: Area Under the Concentration-Time Profile From Time 0 to End of Dosing Interval (AUCtau)

    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.

    Time frame: 0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2

16. Part 1C and Part 1D: Plasma Concentration of Lenalidomide and Pomalidomide

    Plasma concentration of lenalidomide and pomalidomide was measured in this outcome measure.

    Time frame: Cycle 1 (0 hours post dose on Day 1, 8 and 15); Cycle 2 (0 hours on Day 15)

17. Part 1: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06863135

    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).

    Time frame: From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 63.31 months)

18. Part 1: Concentration of Soluble Cytokines in Serum

    The concentration of Interleukin-2, Interleukin-6, Interferon-gamma and tumor necrosis factor-alpha were measured in this outcome measure. Cycle = C.

    Time frame: 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)

19. 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

    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.

    Time frame: 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)

20. Part 2: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters

    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.

    Time frame: 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)

21. Part 2: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters

    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.

    Time frame: 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)

22. Part 2: Number of Participants With Shifts From Grade <=2 to Grade 3 or 4 Post-Baseline in Urinalysis

    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.

    Time frame: 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)

23. Part 2: CRR as Per IMWG Criteria

    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.

    Time frame: 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)

24. Part 2: DoCR as Per IMWG Criteria

    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.

    Time frame: 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)

25. Part 2: TTR as Per IMWG Criteria

    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.

    Time frame: 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)

26. Part 2: DOSD as Per IMWG Criteria

    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.

    Time frame: 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)

27. Part 2: PFS as Per IMWG Criteria

    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.

    Time frame: 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)

28. Part 2: OS

    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.

    Time frame: 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)

29. Part 2: Percentage of Participants With Negative MRD After Treatment With PF-06863135 Using IMWG MRD Criteria

    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.

    Time frame: 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)

30. Part 2: Number of Participants With ADA and NAb Against PF-06863135

    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).

    Time frame: From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 34.3 months)

31. Part 2: Concentration of Soluble Cytokines in Serum

    The concentration of Interleukin-2, Interleukin-6, Interferon-gamma and tumor necrosis factor-alpha were measured in this outcome measure.

    Time frame: 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)

Baseline characteristics

Related links

• To obtain contact information for a study center near you, click here. ↗

Study documents

• Study protocol · Mar 29, 2023
• Statistical analysis plan · Jul 14, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.