Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Subjects With Relapsed and Refractory Multiple Myeloma
Study CC-93269-MM-001 is an open-label, Phase 1, dose escalation (Part A and C) and expansion (Parts B and D), first-in-human clinical study of CC-93269 in subjects with relapsed and refractory multiple myeloma.
The dose escalation parts (Part A with CC-93269 administered intravenous (IV) and Part C subcutaneous (SC)) of the study will evaluate the safety and tolerability of escalating doses of CC-93269, administered IV or SC, to determine the maximum tolerated dose (MTD) and non-tolerated dose (NTD) of CC-93269. The expansion parts (Part B and D) will further evaluate the safety and efficacy of CC-93269 administered IV or SC at or below the MTD in selected expansion cohorts of up to approximately 20 evaluable subjects each in order to determine the Recommended Phase 2 dose (RP2D).One or more dosing regimens may be selected for cohort expansion. All treatments will be administered in 28-day cycles for up to 2 years or extended up to 5 years for subjects maintaining clinical benefit at the discretion of the Safety Review Committee, until confirmed disease progression, unacceptable toxicity, or subject/investigator decision to withdraw.
Arms and Interventions
|Experimental: Administration of CC-93269|
CC-93269 will be administered to each patient on a 28-day cycle
Primary Outcome Measures
- Adverse Events (AEs) [Up to 48 months]
Number of participants with Adverse Events
- Dose Limiting Toxicity (DLT) [Up to 48 months]
Is defined as any of the toxicities occurring within the DLT assessment window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to extraneous causes.
- Non-Tolerated Dose (NTD) [Up to 48 months]
Is defined as a dose level at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in the DLT window.
- Maximum Tolerated Dose (MTD) [Up to 48 months]
Is defined as the last dose cohort below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during the DLT window.
Secondary Outcome Measures
- Overall Response Rate (ORR) [Up to 48 months]
Is defined as the proportion of subjects who achieve a partial response or better (eg, PR, VGPR, CR or sCR), according to International Myeloma Working Group (IMWG) response criteria.
- Time to Response [Up to 48 months]
Is defined as the time from the first CC-93269 dose date to the date of first documented response (PR or better).
- Duration of Response [Up to 48 months]
Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
- Progression Free Survival [Up to 48 months]
Is defined as the time from the first dose of CC-93269 to progressive disease or death from any cause, whichever occurs first.
- Overall Survival [Up to 48 months]
Is defined as the time from the first dose of CC-93269 to death from any cause.
- Pharmacokinetics - Cmax [Up to 48 months]
Maximum serum concentration of drug
- Pharmacokinetics - Cmin [Up to 48 months]
Minimum serum concentration of drug
- Pharmacokinetics - AUC [Up to 48 months]
Area under the curve
- Pharmacokinetics - tmax [Up to 48 months]
Time to peak (maximum) serum concentration
- Pharmacokinetics - t1/2 [Up to 48 months]
- Pharmacokinetics - CL [Up to 48 months]
Apparent total body clearance
- Pharmacokinetics - Vss [Up to 48 months]
Volume of distribution at steady-state
- Pharmacokinetics - accumulation index of CC-93269 [Up to 48 months]
Accumulation ratio of drug
- Presence and frequency of anti-drug antibodies (ADA) [Up to 48 months]
Detection of anti-drug antibodies in participants and frequency of anti-drug antibodies
- Evaluate measures of tumor sensitivity/ resistance to CC-93269 [Up to 48 months]
Measurement of tumor and immune factors
Subjects must satisfy the following criteria to be enrolled in the study:
Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
Subject (male or female) is ≥ 18 years of age the time of signing the ICF.
Subject has non-secretory multiple myeloma, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, or amyloidosis.
Subjects must have measurable disease (as determined by the central lab).
Subject consents to hospitalization for monitoring and collection of study peripheral blood samples.
Subject consents to serial bone marrow aspirations and/or biopsies during Screening, study treatment and at the end of treatment.
Subject has an Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
Subjects must have adequate hematologic, liver, renal, and coagulation function as assessed by laboratory tests.
Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and during the safety follow-up period.
The presence of any of the following will exclude a subject from enrollment:
Subject has received prior therapy directed at B cell maturation antigen (BCMA).
Subject has symptomatic central nervous system involvement of multiple myeloma.
Subject has non-secretory multiple myeloma, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis.
Subject is on chronic systemic immunosuppressive therapy or corticosteroids.
Subjects with clinically significant cardiac disease.
Subject had a prior autologous stem cell transplant ≤ 3 month prior to starting CC-93269.
Subject had a prior allogeneic stem cell transplant ≤ 12 month prior to starting CC-93269.
Subject had a prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting CC-93269, whichever is shorter. Subjects must have recovered from any clinically significant non-hematologic toxicities (ie, to Grade ≤1) of prior systemic anti-cancer directed treatments unless otherwise specified
Subject had major surgery ≤ 2 weeks prior to starting CC-93269.
Subject is a pregnant or lactating female.
Subject has known history or serologic evidence of human immunodeficiency virus (HIV) infection.
Subject has known history, virologic or serological evidence of hepatitis B or C virus (HBV/HCV) infection. Subjects who had HCV but have received an antiviral treatment and show no detectable HCV viral RNA for 6 months are eligible
Subject has a history of a venous thromboembolic event (VTE) within 6 months prior to study entry (eg, deep-vein thrombosis or pulmonary embolism). Subjects with distant history of VTE (ie, occurring > 6 months prior to study entry) who require ongoing treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors) are eligible for study entry.
Subject has a history of concurrent second cancers requiring active, ongoing systemic treatment.
Subject has a history or presence of clinically relevant central nervous system (CNS) pathology.
Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Subject has any condition (eg, active or uncontrolled infection) including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. .
Subject has any condition that confounds the ability to interpret data from the study.
Subject has inadequate pulmonary function.
Subject has active, uncontrolled, or suspected infection.
Subject has pulmonary, cardiac, or hepatic involvement of extramedullary multiple myeloma.
Subjects with a history of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
Recent SARS-CoV-2 vaccine as specified in the protocol.
Contacts and Locations
|1||University of Alabama at Birmingham||Birmingham||Alabama||United States||35294|
|2||University of California San Francisco Medical Center||San Francisco||California||United States||94142|
|3||Yale Cancer Center||New Haven||Connecticut||United States||06510|
|4||Winship Cancer Institute of Emory University||Atlanta||Georgia||United States||30322|
|5||Massachusetts General Hospital||Boston||Massachusetts||United States||02114|
|6||Beth Israel Deaconess Medical Center||Boston||Massachusetts||United States||02215|
|7||Dana Farber Cancer Institute||Boston||Massachusetts||United States||02215|
|8||Henry Ford Medical Center - New Center One||Detroit||Michigan||United States||48202|
|9||Icahn School of Medicine at Mount Sinai Mount Sinai West||New York||New York||United States||10019|
|10||Swedish Cancer Institute||Seattle||Washington||United States||98104|
|11||Universitaetsklinik Hamburg - Eppendorf||Hamburg||Germany||20246|
|13||Azienda Ospedaliera Papa Giovanni XXIII||Bergamo||Italy||24127|
|14||Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)||Meldola||Italy||47014|
|15||Istituto Clinico Humanitas||Milan||Italy||20089|
|16||Vall d´Hebron University Hospital||Barcelona||Spain||08035|
|17||Hospital Universitari Germans Trias i Pujol ICO Badalona||Barcelona||Spain||08916|
|18||Hospital General Gregorio Maranon||Madrid||Spain||28007|
|19||Clinica Universidad de Navarra||Pamplona||Spain||31008|
|20||Hospital Universitario de Salamanca||Salamanca||Spain||37007|
|21||Hospital Universtario Marques de Valdecilla||Santander||Spain||39008|
|22||Hospital de la Fe||Valencia||Spain||46009|
|23||Hospital Universitario Doctor Peset||Valencia||Spain||46017|
|24||Sahlgrenska University Hospital||Gothenborg||Sweden||413 46|
|25||Skanes Universitetssjukhus Lund||Lund||Sweden||SE-221 85|
|26||Karolinska Universitetssjukhuset - Solna||Solna||Sweden||171 76|
|27||Akademiska Hospital Uppsala||Uppsala||Sweden||75158|
Sponsors and Collaborators
- Study Director: Michael R Burgess, MD, PhD, Celgene
Study Documents (Full-Text)None provided.