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

NCT04818372 | Unknown Phase 1

• 1 other identifier: CM313MM001
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 3

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).

Conditions

Multiple Myeloma; Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• 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)

  up to 24 months

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

  up to 24 months

Study Arms (3)

Dose escalation

EXPERIMENTAL

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

Dose expansion _Cohort 1

EXPERIMENTAL

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

Drug: CM313; Drug: Dexamethasone

Dose expansion _Cohort 2

EXPERIMENTAL

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

Drug: CM313; Drug: Dexamethasone; Drug: Lenalidomide

Interventions

CM313-Dose escalation DRUG

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.

Dose escalation

CM313 DRUG

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.

Dose expansion _Cohort 1; Dose expansion _Cohort 2

Dexamethasone DRUG

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

Dose expansion _Cohort 1; Dose expansion _Cohort 2

Lenalidomide DRUG

25 mg/day lenalidomide 21 of 28 days cycle

Dose expansion _Cohort 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Keymed Biosciences Co.Ltd: lead

Study Sites (3)

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

Beijing, Beijing Municipality, China

RECRUITING

Beijing Chao-Yang Hospital

Beijing, Beijing Municipality, China

RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, China

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma

Interventions

Dexamethasone; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Wenming Chen, Dr.

  Beijing Chao Yang Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qian Jia

CONTACT

028-88610620; qianjia@keymedbio.com

Dan Liu

CONTACT

028-88610620; danliu@keymedbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation: Modified 3+3 dose escalation design: an accelerated dose titration design followed by traditional 3+3 dose escalation design

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: March 26, 2021
• Study Start: April 26, 2021
• Primary Completion: January 1, 2023
• Study Completion: April 1, 2023
• Last Updated: November 12, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)