Clinical Trials /

CID-103 (Anti-CD38 Antibody) in Previously Treated Relapsed or Refractory Multiple Myeloma

NCT04758767

Description:

Patients with relapsed/refractory multiple myeloma will be enrolled in a dose-escalation phase receiving monotherapy CID-103. Once the recommended CID-103 dose and infusion duration is known, additional patients will be enrolled in an expansion phase consisting of two cohorts (anti-CD38 pretreated, and anti-CD38 treatment naïve). Patients will be treated until disease progression or unacceptable toxicities.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CID-103 (Anti-CD38 Antibody) in Previously Treated Relapsed or Refractory Multiple Myeloma
  • Official Title: A Phase 1 Dose Escalation and Expansion Study of CID-103, an Anti-CD38 Antibody, in Patients With Previously Treated Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CASI-CID-103-101
  • SECONDARY ID: 2019-004006-10
  • NCT ID: NCT04758767

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CID-103Dose escalation cohort

Purpose

Patients with relapsed/refractory multiple myeloma will be enrolled in a dose-escalation phase receiving monotherapy CID-103. Once the recommended CID-103 dose and infusion duration is known, additional patients will be enrolled in an expansion phase consisting of two cohorts (anti-CD38 pretreated, and anti-CD38 treatment naïve). Patients will be treated until disease progression or unacceptable toxicities.

Detailed Description

      Dose escalation/infusion duration phase:

      During the CID-103 dose escalation/infusion duration phase, only patients diagnosed with
      multiple myeloma who have relapsed or are refractory to at least two prior lines of therapy
      including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody will be
      enrolled. Patients will receive monotherapy CID-103. Dose escalation decisions will be based
      on dose-limiting toxicities; infusion duration decisions will be based on infusion-related
      reactions. The dose taken forward into the expansion phase will be the RP2D determined in the
      dose escalation phase.

      Expansion phase:

      The expansion phase consists of two specific cohorts of patients with relapsed/refractory
      multiple myeloma: 1) Pretreated cohort having received previous treatment with an anti-CD38
      antibody and 2) Naïve cohort in patients for whom an anti-CD38 antibody is unavailable. Eight
      patients will be enrolled into each cohort, and if one or more responses is observed, that
      cohort will be expanded to a total of 14 patients to further assess efficacy. Patients must
      have had at least two prior systemic therapies (mono or combo), including a proteasome
      inhibitor and an immunomodulatory agent. Patients will be treated until disease progression
      or unacceptable toxicities.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation cohortExperimentalMonotherapy CID-103. Priming dose will be given for first dose. Dose and duration of infusion dependent on dose cohort and tolerability.
  • CID-103
Dose expansion cohort - pretreatedExperimentalCID-103 monotherapy at the recommended phase 2 dose
  • CID-103
Dose expansion cohort - NaïveExperimentalCID-103 monotherapy at the recommended phase 2 dose
  • CID-103

Eligibility Criteria

        Inclusion Criteria:

          1. Able and willing to sign the ICF and comply with the protocol

          2. Male or female ≥ 18 years of age

          3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          4. Agrees to bone marrow aspirates

          5. Must have pathologically confirmed multiple myeloma

          6. Has relapsed or refractory myeloma

          7. At least 2 prior systemic anti-cancer therapies for relapsed or refractory multiple
             myeloma, including an immunomodulatory agent and a proteasome inhibitor

          8. Meets all IMWG 2014 criteria at diagnosis

          9. Measurable disease

         10. If female, must be of non-childbearing potential or have a negative pregnancy test at
             screening and use adequate contraception throughout study until 90 days after last
             dose

         11. If male with partner of childbearing potential, be vasectomized or use adequate
             contraception throughout study until 180 days after last dose

         12. All previous therapy-related adverse events should have resolved, prior to Day 1, to
             Grade 1 or baseline value with the exception of alopecia (includes effects of
             radiotherapy)

         13. Adequate organ function as indicated by neutrophils, platelets, hemoglobin, eGFR,
             serum total and direct bilirubin, AST, ALT, INR, aPTT

        Exclusion Criteria:

          1. Received small molecule or tyrosine kinase inhibitor within two weeks or five
             half-lives (whichever is longer) prior to the first dose of study drug; chemotherapy,
             investigational drug or biological cancer therapy within three weeks prior to the
             first dose of study drug; nitrosourea or radioisotope within six weeks prior to first
             dose of study drug, non-recovery to the CTCAE v5 Grade 1 or better from the adverse
             events due to cancer therapeutics administered more than four weeks earlier.

          2. Received an anti-CD38 therapy within four months from first dose of study drug

          3. Inability to perform study baseline RBC type and cross-match, phenotype, genotype or
             lack of available baseline data on RBC phenotype or genotype

          4. Receiving other concurrent investigational therapies or have received investigational
             therapies within four weeks of the first dose of study drug or five half-lives, if
             known, whichever is shorter

          5. Currently receiving systemic steroids unless equivalent to 10 mg/day of prednisone or
             less for adrenal replacement only. At least two weeks since last dose of steroid
             therapy intended for the treatment of myeloma and the first dose of study drug.

          6. Non-secretory myeloma unless measurable plasmacytoma

          7. Known hypersensitivity to CID-103 or any of its excipients

          8. Baseline interval between Q and T wave on electrocardiogram > 480 msec using
             Fridericia's formula (QTcF)

          9. Requires renal dialysis

         10. Sensory or motor neuropathy ≥ Grade 3

         11. Known/clinically significant amyloidosis

         12. Known active central nervous system disease or leptomeningeal plasmacytoma.

         13. Presence of any other active malignancy requiring systemic therapy other than the
             disease under study

         14. Active infection requiring systemic therapy

         15. Active infection with human immunodeficiency virus and CD4+ T-cell count < 350/μL

         16. Active infection with hepatitis B (surface antigen); or infection with hepatitis C in
             absence of sustained virologic response

         17. Therapeutic anticoagulation, meaning any thromboembolic event within the last six
             months prior to first dose of study drug or anticoagulation with therapeutic
             (non-prophylactic) intent

         18. A history or evidence of cardiovascular risk

         19. History or clinical evidence of any surgical or medical condition which the
             investigator judges as likely to interfere with the results of the study or pose an
             additional risk in participating, particularly any pre-existing condition that would
             put the patient at additional risk should they experience an infusion-related reaction

         20. At the time of signing informed consent is a regular user (including
             "recreational/medical use") of any illicit drugs or had a recent history (within the
             last year) of substance abuse (including alcohol)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:approximately 18 months after study start
Safety Issue:
Description:CTCAE v5 coded using the current Medical Dictionary for Regulatory Activities (MedDRA) version

Secondary Outcome Measures

Measure:Recommended Phase 2 dose
Time Frame:approximately 18 months after study start
Safety Issue:
Description:Based primarily on dose-limiting toxicities
Measure:Optimal pre- and post-medication regimens
Time Frame:approximately 18 months after study start
Safety Issue:
Description:Type, incidence, severity, timing, seriousness, and relatedness of AEs and laboratory abnormalities will be compared before and after the changes in pre/post medications are made, with specific focus on IRRs and their symptoms
Measure:Target engagement assays and ex vivo testing
Time Frame:approximately 18 months after study start
Safety Issue:
Description:Extent of RBC binding and cross-match confounding
Measure:Serum concentrations of CID-103
Time Frame:approximately 18 months and 3 years after study start
Safety Issue:
Description:AUC
Measure:Serum concentrations of CID-103
Time Frame:approximately 18 months and 3 years after study start
Safety Issue:
Description:Cmax
Measure:Serum concentrations of CID-103
Time Frame:approximately 18 months and 3 years after study start
Safety Issue:
Description:t1/2
Measure:Serum concentrations of CID-103
Time Frame:approximately 18 months and 3 years after study start
Safety Issue:
Description:volume of distribution
Measure:Serum concentrations of CID-103
Time Frame:approximately 18 months and 3 years after study start
Safety Issue:
Description:accumulation
Measure:Objective response rate
Time Frame:approximately 3 years after study start
Safety Issue:
Description:Based on IMWG
Measure:Duration of response
Time Frame:approximately 3 years after study start
Safety Issue:
Description:Calculated using a Kaplan-Meier method overall and for appropriate subgroups and cohorts, based on IMWG
Measure:Progression-free survival
Time Frame:approximately 3 years after study start
Safety Issue:
Description:Calculated using a Kaplan-Meier method overall and for appropriate subgroups and cohorts, based on IMWG
Measure:Overall survival
Time Frame:approximately 3 years after study start
Safety Issue:
Description:Calculated using a Kaplan-Meier method overall and for appropriate subgroups and cohorts, based on IMWG

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:CASI Pharmaceuticals, Inc.

Trial Keywords

  • multiple myeloma
  • CID-103
  • anti-CD38 antibody

Last Updated

February 17, 2021