Study of Mivavotinib (CB-659) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

NCT ID: NCT05319028

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-23
• Study Completion Date: 2023-02-24

Brief Summary

Study CX-659-401 is a multicenter, open-label, phase 2 study of mivavotinib to evaluate the single-agent activity of mivavotinib in patients with relapsed/refractory non-GCB/ABC DLBCL, incorporating ctDNA-based next-generation sequencing (NGS) to identify DLBCL patients harboring MyD88 and/or CD79B mutations within the study. This goal of this strategy is to evaluate its activity both in the cell-of-origin subgroup of non-GCB/ABC DLBCL and in the genetically defined subgroups of MyD88/CD79B-mutated and wild type DLBCL.

Detailed Description

Approximately 50 patients will be randomized 1:1 to one of two dose/schedule cohorts: one with a continuous dosing schedule (100 mg QD) and one with an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15). Patients will receive treatment with mivavotinib until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Conditions

Non-GCB/ABC Diffuse Large B-Cell Lymphoma; With and Without MyD88 and/or CD79B Mutations

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continuous Dosing Schedule

Mivavotinib 100 mg once daily (QD)

Group Type: EXPERIMENTAL

Mivavotinib

Intervention Type: DRUG

oral tablet

Induction Dosing Schedule

Mivavotinib 120 mg QD for 14 days, then 80 mg QD starting Day 15

Group Type: EXPERIMENTAL

Mivavotinib

Intervention Type: DRUG

oral tablet

Interventions

Mivavotinib

oral tablet

Intervention Type: DRUG

Other Intervention Names

CB-659

Eligibility Criteria

Inclusion Criteria

1. Male or female patients aged 18 years or older

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

3. Life expectancy of > 3 months

4. Histologically confirmed de novo or transformed non-GCB DLBCL.

5. Relapsed or refractory to ≥ 2 prior lines of chemotherapy based on standard of care

6. Patients should not have failed more than 5 prior lines of therapy

7. Must have [18F]Fluorodeoxyglucose-positron emission tomography (FDG-PET)-avid measurable disease that meets the size criteria per International Working Group (IWG) criteria.

8. Must have recovered from adverse events of prior anti-cancer therapy to severity ≤ Grade 1.

9. Adequate organ function as assessed by laboratory values.

10. If female of childbearing potential, agreement to use protocol specified contraception methods. If male, agreement to use an effective barrier method of contraception.

Exclusion Criteria

1. DLBCL with central nervous system (CNS) involvement with active brain or leptomeningeal disease

2. Known human immunodeficiency (HIV; testing not required) or HIV-related malignancy

3. Known hepatitis B surface antigen positive or known or active hepatitis C infection

4. Prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) cell infusion within 90 days of screening

5. Prior allogeneic stem cell transplantation

6. Unstable/inadequate cardiac function

7. Known gastrointestinal (GI) disease or GI procedure that interferes with swallowing/absorption of oral drug

8. Major surgery within 14 days before the first dose of study drug

9. Serious infection (bacterial/fungal/viral) requiring parenteral antibiotic/antiviral therapy for >5 days within 21 days prior to first dose of study drug

10. Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of mivavotinib.

11. Use of medication known to be inhibitors or inducers of P-glycoprotein (P-gp) and/or Cytochrome P (CYP)3A

12. Female patients who are pregnant, lactating or breastfeeding.

13. Any radiation therapy within 3 weeks prior to first dose of study treatment.

14. Systemic anticancer treatment within 3 weeks before first dose of study treatment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Northwestern University

Evanston, Illinois, United States

Henry Ford Health

Detroit, Michigan, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Toledo Clinic Cancer Center

Toledo, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

The University of Texas, M. D. Anderson Cancer Center

Houston, Texas, United States

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Countries

United States

Other Identifiers

CX-659-401

Identifier Type: -

Identifier Source: org_study_id