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

Primary Purpose

Multiple Myeloma, Lymphoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CM313-Dose escalation

CM313

Dexamethasone

Lenalidomide

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%.

Sites / Locations

Beijing Chao-Yang Hospital, Capital Medical University (West Branch)Recruiting
Beijing Chao-Yang HospitalRecruiting
Peking University Third Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Dose escalation

Dose expansion _Cohort 1

Dose expansion _Cohort 2

Arm Description

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).

This cohort will comprise subjects with RRMM. Subjects will receive the CM313 in combination with dexamethasone.

This cohort will comprise subjects with RRMM and NDMM. Subjects will receive the CM313 in combination with Rd regimen.

Outcomes

Primary Outcome Measures

Dose escalation: Number of Participants with a Dose-Limiting Toxicity (DLT)

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

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.

Secondary Outcome Measures

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).

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

Dose escalation and Dose expansion: Incidence of anti-CM313

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04818372

First Posted

March 24, 2021

Last Updated

November 11, 2021

Sponsor

Keymed Biosciences Co.Ltd

1. Study Identification

Unique Protocol Identification Number

NCT04818372

Brief Title

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

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Recruiting

Study Start Date

April 26, 2021 (Actual)

Primary Completion Date

January 2023 (Anticipated)

Study Completion Date

April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Keymed Biosciences Co.Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma, Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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)

Allocation

Non-Randomized

Enrollment

87 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose escalation

Arm Type

Experimental

Arm Description

Arm Title

Dose expansion _Cohort 1

Arm Type

Experimental

Arm Description

This cohort will comprise subjects with RRMM. Subjects will receive the CM313 in combination with dexamethasone.

Arm Title

Dose expansion _Cohort 2

Arm Type

Experimental

Arm Description

This cohort will comprise subjects with RRMM and NDMM. Subjects will receive the CM313 in combination with Rd regimen.

Intervention Type

Drug

Intervention Name(s)

CM313-Dose escalation

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

CM313

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

dexamethasone 40 mg/day at day 1,8,15,22 at 28 days cycle

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Intervention Description

25 mg/day lenalidomide 21 of 28 days cycle

Primary Outcome Measure Information:

Title

Dose escalation: Number of Participants with a Dose-Limiting Toxicity (DLT)

Time Frame

Up to 21 days after the first dose

Title

Time Frame

Up to 30 days after the last dose of CM313 or until the start of subsequent anticancer therapy, if earlier

Title

Dose expansion: To evaluate the activity of CM313 in combination with Rd/Dexamethasone as assessed by overall response rate (ORR) in RRMM patients

Description

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.

Time Frame

Up to 24 months

Secondary Outcome Measure Information:

Title

Time Frame

21 days after the first dose

Title

Time Frame

up to 24 months

Title

Dose escalation and Dose expansion: Incidence of anti-CM313

Time Frame

up to 24 months

Title

Dose escalation: Overall Response Rate (ORR)

Description

ORR is defined as the proportion of participants who have a partial response (PR) or better according to the IMWG criteria.

Time Frame

up to 24 months

Title

Dose escalation and Dose expansion: Clinical Benefit Rate (CBR)

Description

CBR is defined as the proportion of participants who have a minimal response (MR) or better according to the IMWG criteria.

Time Frame

up to 24 months

Title

Dose escalation and Dose expansion: Duration of Response (DOR)

Description

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.

Time Frame

From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (up to 24 months)

Title

Dose escalation and Dose expansion: Time to Response (TTR)

Description

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.

Time Frame

From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (up to 24 months)

Title

Dose escalation and Dose expansion: Progression-Free Survival (PFS)

Description

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.

Time Frame

up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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%.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Qian Jia

Phone

028-88610620

qianjia@keymedbio.com

First Name & Middle Initial & Last Name or Official Title & Degree

Dan Liu

Phone

028-88610620

danliu@keymedbio.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wenming Chen, Dr.

Organizational Affiliation

Beijing Chao Yang Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Chao-Yang Hospital, Capital Medical University (West Branch)

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhongxia Huang

Facility Name

Beijing Chao-Yang Hospital

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wenming Chen, Dr.

Phone

13910107759

13910107759@qq.com

Facility Name

Peking University Third Hospital

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hongmei Jing, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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