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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-GCB/ABC Diffuse Large B-Cell Lymphoma; With and Without MyD88 and/or CD79B Mutations
• Intervention / Treatment: Drug: Mivavotinib

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Administrator; Phone Number: 650-870-1000; Email: clinicaltrials@calithera.com
• Study Contact Backup: Name: Susheela Carroll, PhD; Email: scarroll@calithera.com

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas, M. D. Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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).	CR rate per IRC according to the 2014 IWG Lugano criteria (Cheson, 2014)	Start of treatment to 21 months

Collaborators and Investigators

• Sponsor: Calithera Biosciences, Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: DLBCL; NHL; Relapsed/Refractory; ABC; CD79b; Mivavotinib; MyD88; non-GCB; CB-659
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CX-659-401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No