Clinical trial NCT04818372: Dose Escalation and Expansion Study of CM313 in Subjects With Relapsed or Refractory Multiple Myeloma and Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma
Lymphoma
Lead sponsor: Keymed Biosciences Co.Ltd
Sponsor class: INDUSTRY
First posted: 2021-03-26
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation: Modified 3+3 dose escalation design: an accelerated dose titration design followed by traditional 3+3 dose escalation design
Primary purpose: TREATMENT

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).


Eligibility criteria: Key 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 \<＝2.
* 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 ≤ 1.

Key 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%.

Primary outcomes:
measure: Dose escalation: Number of Participants with a Dose-Limiting Toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: 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
timeFrame: Up to 30 days after the last dose of CM313 or until the start of subsequent anticancer therapy, if earlier
measure: Dose expansion: To evaluate the activity of CM313 in combination with Rd/Dexamethasone as assessed by overall response rate (ORR) in RRMM patients
timeFrame: Up to 24 months
Secondary outcomes:
measure: 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).
timeFrame: 21 days after the first dose
measure: 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
timeFrame: up to 24 months
measure: Dose escalation and Dose expansion: Incidence of anti-CM313
timeFrame: up to 24 months
measure: Dose escalation: Overall Response Rate (ORR)
timeFrame: up to 24 months
measure: Dose escalation and Dose expansion: Clinical Benefit Rate (CBR)
timeFrame: up to 24 months
measure: Dose escalation and Dose expansion: Duration of Response (DOR)
timeFrame: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (up to 24 months)
measure: Dose escalation and Dose expansion: Time to Response (TTR)
timeFrame: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (up to 24 months)
measure: Dose escalation and Dose expansion: Progression-Free Survival (PFS)
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital, Capital Medical University (West Branch)
state: Beijing
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
Study officials:
affiliation: Beijing Chao Yang Hospital
name: Wenming Chen, Dr.
role: PRINCIPAL_INVESTIGATOR
References: