Clinical trial NCT05319028: 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
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2022-04-08
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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).
timeFrame: Start of treatment up to 21 months
measure: Safety as measured by type, incidence, severity, seriousness, and study drug-relatedness of adverse events per Common Terminology Criteria for Adverse Events, version 5
timeFrame: Start of treatment up to 21 months
Secondary outcomes:
measure: Duration of Response (DOR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
timeFrame: Start of treatment up to 21 months
measure: Progression-Free Survival (PFS) as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
timeFrame: Start of treatment up to 21 months
measure: Complete Response (CR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
timeFrame: Start of treatment to 21 months
Other outcomes:
Locations:
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas, M. D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
References: