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A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY AND PHARMACOKINETIC OF PF 06863135, A B CELL MATURATION ANTIGEN (BCMA) CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT IN JAPANESE PARTICIPANTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA

Study of PF 06863135 in Japanese Participants With Multiple Myeloma

4

All of the 4 participants were Japanese and the majority (75.0%) were male and >=65 to <=75 years of age. All 4 participants (100.0%) had an Eastern Cooperative Oncology Group (ECOG) performance status of <=1 and all had measurable disease at baseline. One participant (25.0%) had Revised International Staging System Stage III disease and 1 participant (25.0%) had high cytogenic risk. Two participants (50.0%) had extramedullary disease at baseline. All participants had at least 1 ongoing disease/syndrome at the start of the study. The most frequently (>50% participants) reported ongoing diseases/syndromes included anaemia, constipation, hypokalaemia, cancer pain, and peripheral neuropathy (each 50.0%).

A total of 4 participants were enrolled and received at least 1 dose of study intervention and all 4 participants (100.0%) were included in each analysis population. At the end of the study, all 4 participants had discontinued treatment (2 participants died and 2 participants discontinued treatment due to progressive disease but completed the study).

* All 4 participants (100.0%) in the study experienced at least 1 all-causality treatment emergent AE (TEAE), of which 3 participants (75.0%) experienced a serious AE (SAE). All-causality TEAEs of maximum Grades 3 or 4 were reported in a total of 2 participants (50.0%). Two participants (50.0%) had an all-causality Grade 5 TEAE. No TEAEs associated with permanent discontinuation were reported, 3 participants (75.0%) had TEAEs leading to dose interruption, and 1 participant (25.0%) had TEAEs leading to dose reduction. * All 4 participants (100.0%) in the study experienced at least 1 treatment-related TEAE, of which 3 participants (75.0%) experienced a treatment-related SAE. Treatment-related TEAEs of maximum Grades 3 or 4 were reported in a total of 2 participants (50.0%). Two participants (50.0%) had a treatment-related Grade 5 TEAE. No treatment-related TEAEs associated with permanent discontinuation were reported, 3 participants (75.0%) had treatment-related TEAEs leading to dose interruption, and 1 participant (25.0%) had treatment-related TEAEs leading to dose reduction. * The most frequently reported (>=2 participants [50.0%]) all-causality TEAEs were cytokine release syndrome (CRS) (100.0%), neutropenia and pneumonia (each 75.0%), lymphopenia, diarrhoea, fall, injection site reaction, pyrexia, hypogammaglobulinaemia, and weight decreased (each 50.0%). * The most frequently reported (>=2 participants [50.0%]) treatment-related TEAEs were CRS (100.0%), neutropenia (75.0%), lymphopenia, injection site reaction, pyrexia, hypogammaglobulinaemia, and pneumonia (each 50.0%). * There were 2 deaths during the study treatment period. Both participants died within 90 days after the last dose of study drug. Of the 2 deaths, 1 was a Grade 5 sepsis and the cause of the second death was unknown. The investigator and sponsor considered both the events of death to be treatment-related. * In total, 3 participants (75.0%) reported 5 all-causality SAEs (one event each of Grade 5 sepsis, Grade 5 death, Grade 2 malaise, and two events of Grade 3 pneumonia). All 5 SAEs were considered treatment-related by the investigator. * Three participants (75.0%) experienced all-causality TEAEs (sepsis, pneumonia, malaise, hypogammaglobulinaemia, and pyrexia) leading to dose interruption and 1 participant (25.0%) had an all-causality TEAE (pneumonia) leading to dose reduction. * No participants experienced TEAEs leading to permanent discontinuation of study drug.

Objective Response Rate (ORR): * Among the 4 evaluable participants, the confirmed best overall response as assessed by investigator using International Myeloma Working Group (IMWG) was Complete Response (CR) for 2 participants (50.0%) and Stable Disease (SD) for 2 participants (50.0%). ORR was 50.0% (95% confidence interval: 6.8% to 93.2%). Duration of Response (DOR): * DOR for the 2 participants who had a response (Partial Response [PR] or better) and was 10.38 and 15.01 months, respectively. Progression-Free Survival (PFS): * Of the 4 participants, 2 participants (50.0%) had disease progression and 2 participants (50.0%) died. * For the 2 participants who had a response (PR or better), PFS was 11.95 and 16.16 months, respectively. For the 2 participants who had a response of SD, PFS was 7.85 and 6.47 months, respectively. Overall Survival (OS): * Two participants (50.0%) died at 16.2 and 7.9 months. The remaining 2 participants (50.0%) were alive and continued the OS follow-up until study completion (25.0 and 24.8 months follow-up for these participants, respectively).

The study showed a dose of 1000 microg/kg with a priming dose of 600 microg/kg was well-tolerated in Japanese patients. All participants experienced CRS at least once after the priming dose and no CRS recurrence with subsequent doses. All events were treated with tocilizumab and/or corticosteroid without dose modification. The safety data were consistent with the known safety profile of elranatamab, with no new safety findings. The PK and immunogenicity data showed no new immunogenicity findings.

July. 31, 2024

May. 24, 2024

https://academic.oup.com/jjco/advance-article/doi/10.1093/jjco/hyae068/7681799

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.

https://jrct.mhlw.go.jp/latest-detail/jRCT2021210002

Kawai Norisuke

Pfizer R&D Japan G.K.

Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo

clinical-trials@pfizer.com

Clinical Trials Information Desk

Pfizer R&D Japan G.K.

Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo

+81-3-5309-7000

clinical-trials@pfizer.com

Complete

Mar. 22, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Inclusion Criteria:
*Diagnosis of multiple myeloma (IMWG criteria)
*Measurable disease, as defined by at least 1 of the following
1.Serum myeloma (M) protein >=0.5 g/dL (5 g/L)
2.Urine M protein >=200 mg/24 h
3.Serum free light chain (FLC) >100 mg/L (10 mg/dL) with abnormal kappa:lambda ratio
*Participants must have progressed on or been intolerant of at least 3 prior therapies including proteasome inhibitor, IMID drug and anti-CD38 antibody, either in combination or as a single agent
*ECOG PS 0, 1 or 2. PS 3 is permitted if PS is due solely to bone pain
*Adequate bone marrow, kidney and liver function
*Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1
*Not pregnant and willing to use contraception

Exclusion Criteria:
*Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
*Major surgery within 4 weeks prior to study entry
*Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry
*Radiation therapy within 2 weeks prior to study entry
*History of active autoimmune disorders
*Any form of primary immunodeficiency
*History of severe immune-mediated adverse event with prior immunomodulatory treatment
*Active graft versus host disease other than Grade 1 skin involvement, or that requiring immunosuppressive treatment
*Requirement for systemic immune suppressive medication
*Participant known to be refractory to platelet or red blood cell transfusions
*Current requirement for chronic blood product support
*Active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, known HIV or AIDS related illness and SARS-CoV2
*Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
*Clinically significant cardiovascular in the previous 6 months
*Hypertension that cannot be controlled by medications
*Previous administration with an investigational drug within 4 weeks or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
*Known or suspected hypersensitivity to component of PF 06863135, murine and bovine products

Both

Relapsed or Refractory Multiple Myeloma

Drug: PF-06863135
BCMA-CD3 bispecific antibody

Primary Outcome Measures :
1.Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: up to 28 days ]

Secondary Outcome Measures :
1.frequency of treatment-emergent adverse events [ Time Frame: approximately 2 years ]
2.frequency of laboratory abnormalities [ Time Frame: approximately 2 years ]
3.Maximum plasma concentration (Cmax) of PF-06863135 [ Time Frame: 4 weeks ]
4.immunogenicity of PF-06863135 [ Time Frame: approximately every 1 to 3 cycles (approximately 2 years) ]
5.overall response rate [ Time Frame: approximately every 3 weeks for approximately 2 years ]
6.time to response [ Time Frame: approximately every 3 weeks (approximately 2 years) ]
7.duration of response [ Time Frame: approximately every 3 weeks (approximately 2 years) ]
8.progression free survival [ Time Frame: approximately every 3 weeks (approximately 2 years) ]
9.overall survival [ Time Frame: approximately every 3 months (approximately 2 years) ]
10.minimal residual disease [ Time Frame: approximately 2 years ]
11.systemic soluble immune factors [ Time Frame: approximately 9 months ]
12.area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-06863135 [ Time Frame: 4 weeks ]
13.Trough serum concentrations of PF-06863135 [ Time Frame: approximately 2 years ]

Jan. 05, 2021

none