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

Primary Purpose

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

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Mivavotinib

About this trial

This is an interventional treatment trial for Non-GCB/ABC Diffuse Large B-Cell Lymphoma focused on measuring Mivavotinib, DLBCL, MyD88, CD79b, non-GCB, ABC, NHL, CB-659, Relapsed/Refractory

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Northwestern University
Henry Ford Health
University Hospitals Cleveland Medical Center
Toledo Clinic Cancer Center
University of Pennsylvania
The University of Texas, M. D. Anderson Cancer Center
The University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Continuous Dosing Schedule

Induction Dosing Schedule

Arm Description

Mivavotinib 100 mg once daily (QD)

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

Outcomes

Primary Outcome Measures

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.

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

Secondary Outcome Measures

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

DOR per IRC. DOR will be calculated as the time between the first documentation of partial response (PR) or a complete response (CR) to the first documentation of progressive disease or death, whichever occurs first.

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

PFS per IRC. PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the IRC or death from any cause, whichever occurs first.

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

CR rate per IRC according to the 2014 IWG Lugano criteria (Cheson, 2014)

Full Information

NCT ID

NCT05319028

First Posted

April 1, 2022

Last Updated

March 31, 2023

Sponsor

Calithera Biosciences, Inc

1. Study Identification

Unique Protocol Identification Number

NCT05319028

Brief Title

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

Official Title

A Phase 2 Study of Mivavotinib in Biomarker-Defined Subgroups of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

Sponsor Decision

Study Start Date

June 23, 2022 (Actual)

Primary Completion Date

February 24, 2023 (Actual)

Study Completion Date

February 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Calithera Biosciences, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

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

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Continuous Dosing Schedule

Arm Type

Experimental

Arm Description

Mivavotinib 100 mg once daily (QD)

Arm Title

Induction Dosing Schedule

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Mivavotinib

Other Intervention Name(s)

CB-659

Intervention Description

oral tablet

Primary Outcome Measure Information:

Title

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).

Description

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

Time Frame

Start of treatment up to 21 months

Title

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

Description

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

Time Frame

Start of treatment up to 21 months

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Start of treatment up to 21 months

Title

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

Description

PFS per IRC. PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the IRC or death from any cause, whichever occurs first.

Time Frame

Start of treatment up to 21 months

Title

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

Description

CR rate per IRC according to the 2014 IWG Lugano criteria (Cheson, 2014)

Time Frame

Start of treatment to 21 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Facility Information:

Facility Name

Northwestern University

City

Evanston

State/Province

Illinois

ZIP/Postal Code

60208

Country

United States

Facility Name

Henry Ford Health

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

University Hospitals Cleveland Medical Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Toledo Clinic Cancer Center

City

Toledo

State/Province

Ohio

ZIP/Postal Code

43623

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

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

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

The University of Texas Health Science Center at San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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