Dose Escalation and Expansion Study of CM313 in Subjects With Relapsed or Refractory Multiple Myeloma and Lymphoma

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Multiple Myeloma, Lymphoma

Intervention / Treatment
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* Drug: CM313-Dose escalation
* Drug: CM313
* Drug: Dexamethasone
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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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%.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose Escalation: Modified 3+3 dose escalation design: an accelerated dose titration design followed by traditional 3+3 dose escalation design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>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). | Drug: CM313-Dose escalation<br>* Subjects 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.<br>|
| Experimental: Dose expansion _Cohort 1<br>This cohort will comprise subjects with RRMM. Subjects will receive the CM313 in combination with dexamethasone. | Drug: CM313<br>* Subjects will have 8 infusions at weekly intervals, and then 8 infusions at bi-weekly intervals. After that CM313 will be given every 4 weeks until disease progression or unacceptable toxicity.<br>Drug: Dexamethasone<br>* dexamethasone 40 mg/day at day 1,8,15,22 at 28 days cycle<br>|
| Experimental: Dose expansion _Cohort 2<br>This cohort will comprise subjects with RRMM and NDMM. Subjects will receive the CM313 in combination with Rd regimen. | Drug: CM313<br>* Subjects will have 8 infusions at weekly intervals, and then 8 infusions at bi-weekly intervals. After that CM313 will be given every 4 weeks until disease progression or unacceptable toxicity.<br>Drug: Dexamethasone<br>* dexamethasone 40 mg/day at day 1,8,15,22 at 28 days cycle<br>Drug: Lenalidomide<br>* 25 mg/day lenalidomide 21 of 28 days cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation: Number of Participants with a Dose-Limiting Toxicity (DLT) |  | 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 |  | Up to 30 days after the last dose of CM313 or until the start of subsequent anticancer therapy, if earlier | 
| Dose expansion: To evaluate the activity of CM313 in combination with Rd/Dexamethasone as assessed by overall response rate (ORR) in RRMM patients | 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. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 and Dose expansion: Incidence of anti-CM313 |  | up to 24 months | 
| Dose escalation: Overall Response Rate (ORR) | ORR is defined as the proportion of participants who have a partial response (PR) or better according to the IMWG criteria. | up to 24 months | 
| Dose escalation and Dose expansion: Clinical Benefit Rate (CBR) | CBR is defined as the proportion of participants who have a minimal response (MR) or better according to the IMWG criteria. | up to 24 months | 
| Dose escalation and Dose expansion: Duration of Response (DOR) | DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of PD, per IMWG criteria.or better according to the IMWG criteria. | 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) | TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better. | 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) | PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first. | up to 24 months |