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

Sponsor

Calithera Biosciences, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05319028

Collaborator

(none)

Enrollment

Locations

Arms

19.3

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Non-GCB/ABC Diffuse Large B-Cell Lymphoma With and Without MyD88 and/or CD79B Mutations	Drug: Mivavotinib	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 23, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Continuous Dosing Schedule Mivavotinib 100 mg once daily (QD)	Drug: Mivavotinib oral tablet Other Names: CB-659
Experimental: Induction Dosing Schedule Mivavotinib 120 mg QD for 14 days, then 80 mg QD starting Day 15	Drug: Mivavotinib oral tablet Other Names: CB-659

Arm

Intervention/Treatment

Experimental: Continuous Dosing Schedule

Mivavotinib 100 mg once daily (QD)

Drug: Mivavotinib

oral tablet

Other Names:

CB-659

Experimental: Induction Dosing Schedule

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

Drug: Mivavotinib

oral tablet

Other Names:

CB-659

Outcome Measures

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). [Start of treatment up to 21 months]
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 [Start of treatment up to 21 months]
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). [Start of treatment up to 21 months]
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). [Start of treatment up to 21 months]
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). [Start of treatment to 21 months]
CR rate per IRC according to the 2014 IWG Lugano criteria (Cheson, 2014)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts 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