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

NCT05319028 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CX-659-401
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

Mivavotinib; DLBCL; MyD88; CD79b; non-GCB; ABC; NHL; CB-659; Relapsed/Refractory

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) as assessed by an independent radiology review committee (IRC) according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).

  Overall response is defined as a complete response (CR) or partial response (PR). ORR is the proportion of participants who have overall responses.

  Start of treatment up to 21 months

• Safety as measured by type, incidence, severity, seriousness, and study drug-relatedness of adverse events per Common Terminology Criteria for Adverse Events, version 5

  Type, incidence, severity, seriousness, and study drug-relatedness of AEs assessed by CTCAE v5.0

  Start of treatment up to 21 months

Secondary Outcomes (3)

• Duration of Response (DOR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).

  Start of treatment up to 21 months

• Progression-Free Survival (PFS) as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).

  Start of treatment up to 21 months

• Complete Response (CR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).

  Start of treatment to 21 months

Study Arms (2)

Continuous Dosing Schedule

EXPERIMENTAL

Mivavotinib 100 mg once daily (QD)

Drug: Mivavotinib

Induction Dosing Schedule

EXPERIMENTAL

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

Drug: Mivavotinib

Interventions

Mivavotinib DRUG

oral tablet

Also known as: CB-659

Continuous Dosing Schedule; Induction Dosing Schedule

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 years or older
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Life expectancy of \> 3 months
• Histologically confirmed de novo or transformed non-GCB DLBCL.
• Relapsed or refractory to ≥ 2 prior lines of chemotherapy based on standard of care
• Patients should not have failed more than 5 prior lines of therapy
• Must have \[18F\]Fluorodeoxyglucose-positron emission tomography (FDG-PET)-avid measurable disease that meets the size criteria per International Working Group (IWG) criteria.
• Must have recovered from adverse events of prior anti-cancer therapy to severity ≤ Grade 1.
• Adequate organ function as assessed by laboratory values.
• If female of childbearing potential, agreement to use protocol specified contraception methods. If male, agreement to use an effective barrier method of contraception.

You may not qualify if:

• DLBCL with central nervous system (CNS) involvement with active brain or leptomeningeal disease
• Known human immunodeficiency (HIV; testing not required) or HIV-related malignancy
• Known hepatitis B surface antigen positive or known or active hepatitis C infection
• Prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) cell infusion within 90 days of screening
• Prior allogeneic stem cell transplantation
• Unstable/inadequate cardiac function
• Known gastrointestinal (GI) disease or GI procedure that interferes with swallowing/absorption of oral drug
• Major surgery within 14 days before the first dose of study drug
• Serious infection (bacterial/fungal/viral) requiring parenteral antibiotic/antiviral therapy for \>5 days within 21 days prior to first dose of study drug
• Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of mivavotinib.
• Use of medication known to be inhibitors or inducers of P-glycoprotein (P-gp) and/or Cytochrome P (CYP)3A
• Female patients who are pregnant, lactating or breastfeeding.
• Any radiation therapy within 3 weeks prior to first dose of study treatment.
• Systemic anticancer treatment within 3 weeks before first dose of study treatment

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (7)

Northwestern University

Evanston, Illinois, 60208, United States

Location

Henry Ford Health

Detroit, Michigan, 48202, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

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

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 8, 2022
• Study Start: June 23, 2022
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: April 4, 2023

Record last verified: 2023-03

Locations

US (7)