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.
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
Interventions
Drug | Synonyms | Arms |
---|
CID-103 | | Dose 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
Name | Type | Description | Interventions |
---|
Dose escalation cohort | Experimental | Monotherapy CID-103. Priming dose will be given for first dose. Dose and duration of infusion dependent on dose cohort and tolerability. | |
Dose expansion cohort - pretreated | Experimental | CID-103 monotherapy at the recommended phase 2 dose | |
Dose expansion cohort - Naïve | Experimental | CID-103 monotherapy at the recommended phase 2 dose | |
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: | PK - AUC of CID-103 |
Time Frame: | approximately 18 months and 3 years after study start |
Safety Issue: | |
Description: | AUC of CID-103 in serum |
Measure: | PK - Cmax of CID-103 |
Time Frame: | approximately 18 months and 3 years after study start |
Safety Issue: | |
Description: | Cmax of CID-103 in serum |
Measure: | PK - t1/2 of CID-103 |
Time Frame: | approximately 18 months and 3 years after study start |
Safety Issue: | |
Description: | half-life of CID-103 in serum |
Measure: | PK - Vd of CID-103 |
Time Frame: | approximately 18 months and 3 years after study start |
Safety Issue: | |
Description: | volume of distribution of CID-103 in serum |
Measure: | PK - accumulation of CID-103 |
Time Frame: | approximately 18 months and 3 years after study start |
Safety Issue: | |
Description: | accumulation of CID-103 in serum |
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: | Recruiting |
Lead Sponsor: | CASI Pharmaceuticals, Inc. |
Trial Keywords
- multiple myeloma
- CID-103
- anti-CD38 antibody
Last Updated
May 4, 2021