Study of PF-06863135 Monotherapy and PF-06863135 + Daratumumab Versus Daratumumab + Pomalidomide + Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma

JRCT ID: jRCT2041210098

Registered date:02/11/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: relapsed/refractory multiple myeloma
• Date of first enrollment: 11/01/2022
• Target sample size: 476
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,Finland,Japan,France,Japan,Germany,Japan,Greece,Japan,Italy,Japan,Korea, Republic of,Japan,Mexico,Japan,Netherlands,Japan,New Zealand,Japan,Norway,Japan,Poland,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Part 1 Safety Lead-In Dose Level-1:
- PF-06863135 Level -1, Daratumumab
- PF-06863135 Level 1, Daratumumab

Part 2 Randomized:
- Arm A: PF-06863135 Level 1
- Arm B: PF-06863135 Level 1, Daratumumab
- Arm C: Daratumumab, Pomalidomide, Dexamethasone

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Part 1 Safety Lead-In: Incidence of dose limiting toxicities [ Time Frame: First 42 days after first PF-06863135 dose ]
2.Part 2 Randomized: Progression free survival by blinded independent central review per International Myeloma Working Group criteria [PF-06863135 (Arm A) vs daratumumab + pomalidomide + dexamethasone (Arm C)] [ Time Frame: From date of randomization to date of progressive disease, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 32 months ]
3.Part 2 Randomized: Progression free survival by blinded independent central review per International Myeloma Working Group criteria [PF-06863135 + daratumumab (Arm B) vs. daratumumab + pomalidomide + dexamethasone (Arm C)] [ Time Frame: From date of randomization to date of progressive disease, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 32 months ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion Criteria
1.Male and female participants of childbearing potential must agree to use contraception.
2.Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3.Prior diagnosis of multiple myeloma as defined by IMWG criteria.
4.Measurable disease based on IMWG criteria as defined by at least 1 of the following:
a.Serum M-protein >=0.5 g/dL by SPEP.
b.Urinary M-protein excretion >=200 mg/24 hours by UPEP.
c.Serum immunoglobulin FLC >=10 mg/dL (>=100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
5.Prior anti-multiple myeloma therapy:
a.Part 1: At least 3 prior lines of anti-multiple myeloma therapy including treatment with lenalidomide and a proteasome inhibitor.
b.Part 2: At least 2 prior lines of anti-multiple myeloma therapy including treatment with lenalidomide and a proteasome inhibitor.
6.ECOG performance status <=1.
7.LVEF >=40% as determined by a MUGA scan or ECHO.
8.Adequate hepatic function characterized by the following:
a.Total bilirubin <=1.5 x upper limit of normal.
b.Aspartate aminotransferase <=2.5 x upper limit of normal and alanine aminotransferase <=2.5 x upper limit of normal.
9.Estimated creatinine clearance >=30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or per the local institutional standard method).
10.Adequate bone marrow function characterized by the following:
a.Absolute neutrophil count >=1.0 * 10^9/L (use of granulocyte-colony stimulating factors is permitted if completed at least 28 days prior to planned start of dosing).
b.Platelet count >=75,000/microL if < 50% of bone marrow nucleated cells are plasma cells, or >=50,000/microL if >=50% of bone marrow nucleated cells are plasma cells (transfusion support is permitted if completed at least 28 days prior to planned start of dosing).
c.Hemoglobin >=8 g/dL (transfusion support is permitted if completed at least 28 days prior to planned start of dosing).
11.Corrected serum calcium <=14 mg/dL (<=3.5 mmol/L), or free ionized calcium <=6.5 mg/dL (<=1.6 mmol/L).
12.Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade <=1.
13.Capable of giving signed informed consent.

Exclude criteria

Exclusion Criteria
1.Smoldering multiple myeloma.
2.Plasma cell leukemia.
3.Systemic amyloid light chain amyloidosis.
4.POEMS Syndrome.
5.Stem cell transplant within 12 weeks prior to enrolment, or active graft versus host disease.
6.Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrolment:
a.Acute myocardial infarction or acute coronary syndromes.
b.Clinically significant cardiac arrhythmias.
c.Thromboembolic or cerebrovascular events.
d.Prolonged QT syndrome (or QTcF >470 msec at screening).
7.Ongoing Grade 2 or higher peripheral sensory or motor neuropathy.
8.History of Guillain-Barre syndrome (GBS) or GBS variants, or history of any Grade >=3 peripheral motor polyneuropathy.
9.Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrolment.
10.Any other active malignancy within 3 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
11.Known or suspected hypersensitivity to the study interventions or any of their excipients.
12.Other surgical (including major surgery within 14 days prior to enrolment), medical or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
13.Previous treatment with a BCMA-directed therapy.
14.Anti-CD38-directed therapy within 6 months preceding the first dose of treatment in this study.
15.Part 2 only: Refractory to prior anti-CD38-directed therapy (disease progression while on or within 60 days of the last dose of any anti-CD38-directed therapy, regardless of response).
16.Part 2 only: Previous pomalidomide therapy.
17.Concurrent or anticipated use of a non-topical medication known to be a strong CYP1A2 inhibitor within 7 days prior to first dose of study intervention and throughout study duration.
18.Live attenuated vaccine must not be administered within 4 weeks of the first dose of study intervention.
19.Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). A participant may be eligible if they are in the follow-up phase of an investigational study if they meet the criteria for time elapsed from previous administration of investigational product. Cases must be discussed with sponsor's medical monitor to judge eligibility.
20.For females of childbearing potential: Serum pregnancy test positive at screening.
21.Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (assuming no drug interaction potential).
22.Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05020236