Sponsor Decision

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.

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.

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