Clinical Trials /

A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

NCT04036461

Description:

Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), First-in-Human (FIH) clinical study of CC-99712 in subjects with relapsed and refractory multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-99712, administered intravenously (IV), to determine the maximum tolerated dose (MTD) and non-tolerated dose (NTD) of CC-99712 using a modified accelerated titration design and Bayesian methodology. The MTD and NTD may be established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety and efficacy of CC-99712 administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more dosing regimens may be selected for cohort expansion. All subjects will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or subject/Investigator decision to withdraw.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
  • Official Title: A Phase 1, Multicenter, Open-label, Dose Finding Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CC-99712-MM-001
  • SECONDARY ID: U1111-1231-9404
  • NCT ID: NCT04036461

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CC-99712Administration of CC-99712

Purpose

Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), First-in-Human (FIH) clinical study of CC-99712 in subjects with relapsed and refractory multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-99712, administered intravenously (IV), to determine the maximum tolerated dose (MTD) and non-tolerated dose (NTD) of CC-99712 using a modified accelerated titration design and Bayesian methodology. The MTD and NTD may be established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety and efficacy of CC-99712 administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more dosing regimens may be selected for cohort expansion. All subjects will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or subject/Investigator decision to withdraw.

Trial Arms

NameTypeDescriptionInterventions
Administration of CC-99712ExperimentalCC-99712 will be administered via intravenous (IV) infusion once per 21-days on a Once every three weeks (Q3W) schedule, and once per 28-days on a Once every four weeks (Q4W) schedule
  • CC-99712

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Subject (male or female) is ≥ 18 years of age at the time of signing the ICF.

          2. Subject has a history of MM with relapsed and refractory disease, and must:

               -  Have disease that is nonresponsive while on their last antimyeloma therapy or
                  documented disease progression on or within 60 days from the last dose of their
                  last antimyeloma therapy; and,

               -  Must have received at least 3 prior MM treatment regimens. and,

               -  Must have received a proteasome inhibitor, an immunomodulatory agent and an
                  anti-CD38 antibody (eg, daratumumab); and,

               -  Should have failed treatment with or are intolerant to all established therapies.

          3. Subjects must have measurable disease, including at least one of the criteria below:

               -  M-protein quantities ≥ 0.5 g/dL by sPEP or

               -  ≥ 200 mg/24 hours urine collection by uPEP or

               -  Serum FLC levels > 100 mg/L (milligrams/liter involved light chain) and an
                  abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine
                  M-protein or

               -  For subjects with immunoglobulin class A (IgA) myeloma whose disease can only be
                  reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥
                  0.50 g/dL.

          4. Subject has an ECOG PS of 0-1.

          5. Subjects must have the following laboratory values (determined by local laboratory):

               -  Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L

               -  Platelets (plt) ≥ 75 x 10^9/L.

               -  Potassium within normal limits or correctable with supplements.

               -  Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤
                  2.5 x upper limit of normal (ULN).

               -  Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.0 x ULN for subjects with documented
                  Gilbert's syndrome).

               -  Estimated serum creatinine clearance of ≥ 60 mL/min

               -  International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time
                  (PTT) < 1.5 x ULN.

          6. Females of childbearing potential (FCBP) must:

               -  Either commit to true abstinence from heterosexual contact (which must be
                  reviewed on a monthly basis and source documented) or agree to use, and be able
                  to comply with, at least two effective contraceptive methods (oral, injectable,
                  or implantable hormonal contraceptive; tubal ligation; intra-uterine device;
                  barrier contraceptive with spermicide; or vasectomized partner), one of which
                  must be barrier, from signing the ICF, throughout the study, during dose
                  interruptions, and for up to 42 days following the last dose of CC-99712; and

               -  Have two negative pregnancy tests as verified by the Investigator prior to
                  starting CC-99712. Subject must agree to ongoing pregnancy testing during the
                  course of the study, and after end of study treatment. This applies even if the
                  subject practices true abstinence from heterosexual contact. The subject may not
                  receive IP until the Investigator has verified that the result of the pregnancy
                  test is negative.

                    -  a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at
                       Screening

                    -  a negative serum or urine pregnancy test (Investigator's discretion) within
                       72 hours prior to Cycle 1 Day -1 of study treatment, and within 72 hours
                       prior to Day -1 of every subsequent cycle (note that the Screening serum
                       pregnancy test can be used as the test prior to Day -1 study treatment if it
                       is performed within the prior 72 hours). A serum or urine pregnancy test
                       (investigators discretion) must also be performed at the end of study for
                       each FCBP.

               -  Avoid conceiving for 42 days after the last dose of CC-99712.7. Males must
                  practice true abstinence (which must be reviewed on a monthly basis) or agree to
                  use a condom (a latex condom is recommended) during sexual contact with a
                  pregnant female or a FCBP and will avoid conceiving from signing the ICF, while
                  participating in the study, during dose interruptions, and for at least 42 days
                  following CC-99712 discontinuation, even if he has undergone a successful
                  vasectomy.

        8. Subject is willing and able to adhere to the study visit schedule and other protocol
        requirements.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. In Part A only, subject has received prior investigational therapy directed at BCMA.

          2. Subject has symptomatic central nervous system involvement of MM.

          3. Subject has nonsecretory MM, plasma cell leukemia, Waldenstrom's macroglobulinemia,
             POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes), or amyloidosis.

          4. Subjects with a history of class III or IV congestive heart failure (CHF) or severe
             non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular
             arrhythmia within the previous 6 months prior to signing ICF.

          5. Subject had a prior autologous stem cell transplant ≤ 3 months prior to starting
             CC-99712.

          6. Subject had a prior allogeneic stem cell transplant with either standard or reduced
             intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic
             immunosuppression for graft-versus host disease.

          7. Subject had a prior chimeric antigen receptor T (CAR T) cell product ≤ 4 weeks prior
             to starting CC-99712.

          8. Subject had a prior systemic cancer-directed treatments or investigational modalities
             within 5 pharmacokinetic half-lives or 2 weeks prior to starting CC-99712, whichever
             is longer. The only exception is emergency use of a short course of corticosteroids
             (equivalent of dexamethasone 40 mg/day for a maximum 4 days) before treatment.

          9. Subject had major surgery ≤ 2 weeks prior to starting CC-99712. Subjects must have
             recovered from any clinically significant effects of recent surgery.

         10. Subject is a pregnant or lactating female.

         11. Subject has known human immunodeficiency virus (HIV) infection.

         12. Subject has known history of chronic, active hepatitis B or C virus (HBV/HCV)
             infection.

         13. Subject requires ongoing treatment with chronic, therapeutic dosing of anti-coagulants
             (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).

         14. Subject has a history of concurrent second cancers requiring active, ongoing systemic
             treatment.

         15. Subject has known history of cirrhosis or has clinically significant liver or biliary
             disease. Subjects with stable chronic liver or biliary disease (such as Gilbert's
             syndrome, asymptomatic gallstones, or hepatobiliary involvement of malignancy) may
             participate in the study, however, sponsor medical monitor must be contacted for a
             discussion before enrollment.

         16. Subject has a history of clinically significant corneal disease requiring therapy or
             ongoing active corneal disease.

         17. Subject has active peripheral neuropathy or neuropathic pain Grade 2 or higher, as
             defined by the National Cancer Institute Common Terminology Criteria for Adverse
             Events (NCI-CTCAE v5.0).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From enrollment until at least 42 days after completion of study treatment
Safety Issue:
Description:Number of subjects with adverse event

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the proportion of subjects who achieve a partial response or better (eg, Partial response (PR), Very good partial response (VGPR), Complete response (CR) or sCR), according to IMWG response criteria.
Measure:Time to Response
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the first CC-99712 dose date to the date of first documented response (PR or better).
Measure:Duration of Response
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
Measure:Progression-free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the first dose of CC-99712 to progressive disease (PD) or death from any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the first dose of CC-99712 to death from any cause.
Measure:Pharmacokinetics- Cmax
Time Frame:Up to 3 years
Safety Issue:
Description:Maximum plasma concentration of drug
Measure:Pharmacokinetics- Cmin
Time Frame:Up to 3 years
Safety Issue:
Description:Minimum plasma concentration of drug
Measure:Pharmacokinetics- AUC
Time Frame:Up to 3 years
Safety Issue:
Description:Area under the curve
Measure:Pharmacokinetics- tmax
Time Frame:Up to 3 years
Safety Issue:
Description:Time to peak (maximum) serum concentration
Measure:Pharmacokinetics- t1/2
Time Frame:Up to 3 years
Safety Issue:
Description:Half-life
Measure:Pharmacokinetics- CL
Time Frame:Up to 3 years
Safety Issue:
Description:Clearance
Measure:Pharmacokinetics- Vss
Time Frame:Up to 3 years
Safety Issue:
Description:Volume of Distribution
Measure:Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection
Time Frame:Up to 3 years
Safety Issue:
Description:Anti-CC-99712 antibodies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Multiple Myeloma
  • Relapsed and refractory
  • CC-99712
  • BCMA
  • Antibody drug conjugate

Last Updated

October 30, 2019