A Phase I, Multiple Center, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CM313 in Subjects With Relapsed or Refractory Multiple Myeloma and Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- CM313-Dose escalation
- Conditions
- Multiple Myeloma
- Sponsor
- Keymed Biosciences Co.Ltd
- Enrollment
- 87
- Locations
- 3
- Primary Endpoint
- Dose expansion: To evaluate the activity of CM313 in combination with Rd/Dexamethasone as assessed by overall response rate (ORR) in RRMM patients
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a multi-center, open-label, dose escalation and dose expansion, Phase 1 study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of CM313.
The dose escalation part will determine the MTD of CM313 in subjects with relapsed and/or refractory multiple myeloma (RRMM) or lymphoma based on a modified 3+3 dose escalation design (an accelerated dose titration design followed by traditional 3+3 dose escalation design).
The dose expansion part includes two cohorts. Cohort 1 will evaluate the safety and preliminary anti-tumor activity of CM313 in combination with Dexamethasone in subjects with RRMM. Cohort 2 will evaluate the safety and preliminary anti-tumor activity of CM313 in combination with Rd regimen (Lenalidomide/Dexamethasone) in subjects with RRMM or newly diagnosed MM (NDMM).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Dose escalation: subjects with RRMM who have progressed on, or could not tolerate, all available established therapies and subjects with recurrent and refractory lymphoma.
- •Dose expansion_cohort 1: subjects with RRMM who have progressed on, or could not tolerate, all available established therapies.
- •Dose expansion_cohort 2: subjects with RRMM who have progressed on, or could not tolerate, all available established therapies, or subjects with NDMM.
- •For MM: Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria.
- •For MM: Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 0.5 gram per deciliter (g/dL) or urine M-protein level \>=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) \>= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
- •Eastern Cooperative Oncology Group (ECOG) performance status score \<＝
- •Women of childbearing potential and male subjects must agree to remain abstinent or use contraceptive methods as defined by the protocol.
- •Side effects of any prior therapy or procedures for any medical condition has recovered to NCI-CTCAE v.5.0 Grade ≤
Exclusion Criteria
- •Previous treatment with any anti-CD38 therapy.
- •Subjects with concurrent plasma cell leukemia.
- •Received a cumulative dose of corticosteroids equivalent to greater than or equal to ( \>=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication).
- •Vaccinated with live, attenuated vaccine within 4 weeks prior to the first dose.
- •Received an allogenic stem cell transplant or an autologous stem cell transplant within 3 months before first dose of study drug.
- •Central nervous system (CNS) involvement.
- •The forced expiratory volume in one second (FEV1)\<60%.
Arms & Interventions
Dose escalation
Subjects enrolled in this arm will receive a single dose of CM313 followed by a 3-week period for DLT observation. After that subjects will have 6 infusions at weekly intervals. Dose escalation will be carried out according to a modified 3+3 dose-escalation design. Accelerated dose titration design will be used for the first 4 dose levels (0.006mg/kg, 0.06mg/kg, 0.3mg/kg and 1.0mg/kg) and then traditional 3+3 dose escalation design will be used for the following levels (2.0mg/kg, 4.0mg/kg, 8.0mg/kg, 16mg/kg and 24mg/kg).
Intervention: CM313-Dose escalation
Dose expansion _Cohort 1
This cohort will comprise subjects with RRMM. Subjects will receive the CM313 in combination with dexamethasone.
Intervention: CM313
Dose expansion _Cohort 1
This cohort will comprise subjects with RRMM. Subjects will receive the CM313 in combination with dexamethasone.
Intervention: Dexamethasone
Dose expansion _Cohort 2
This cohort will comprise subjects with RRMM and NDMM. Subjects will receive the CM313 in combination with Rd regimen.
Intervention: CM313
Dose expansion _Cohort 2
This cohort will comprise subjects with RRMM and NDMM. Subjects will receive the CM313 in combination with Rd regimen.
Intervention: Dexamethasone
Dose expansion _Cohort 2
This cohort will comprise subjects with RRMM and NDMM. Subjects will receive the CM313 in combination with Rd regimen.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Dose expansion: To evaluate the activity of CM313 in combination with Rd/Dexamethasone as assessed by overall response rate (ORR) in RRMM patients
Time Frame: Up to 24 months
ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.
Dose escalation: Number of Participants with a Dose-Limiting Toxicity (DLT)
Time Frame: Up to 21 days after the first dose
Dose escalation and Dose expansion: Incidence, severity, and outcome of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Time Frame: Up to 30 days after the last dose of CM313 or until the start of subsequent anticancer therapy, if earlier
Secondary Outcomes
- Dose escalation and Dose expansion: Incidence of anti-CM313(up to 24 months)
- Dose escalation: AUC to the last quantifiable concentration [AUC(0-last)], over the dosing interval [AUC(0-tau)], extrapolated to infinity [AUC(0-inf), time to Cmax (tmax), apparent half-life (t1/2), systemic clearance (CL).(21 days after the first dose)
- Dose escalation and Dose expansion: AUC(0-last), AUC(0-tau), Cmax, t1/2, systemic clearance (CL), volume of distribution (Vz, Vss), minimum concentration (Cmin), Ctrough, accumulation ratios for Cmax and AUC(0-tau) for multiple doses(up to 24 months)
- Dose escalation: Overall Response Rate (ORR)(up to 24 months)
- Dose escalation and Dose expansion: Clinical Benefit Rate (CBR)(up to 24 months)
- Dose escalation and Dose expansion: Duration of Response (DOR)(From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (up to 24 months))
- Dose escalation and Dose expansion: Time to Response (TTR)(From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (up to 24 months))
- Dose escalation and Dose expansion: Progression-Free Survival (PFS)(up to 24 months)