Contributions
Abstract: PB1434
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
R-CHOP remains the standard of care for DLBCL. Although most patients can be cured, 35–40% will experience relapsed/refractory disease, leading to poor outcomes in the majority of patients. Covalent irreversible Bruton tyrosine kinase inhibitors (BTKi) have shown higher responses in patients with non-GCB DLBCL than with GCB DLBCL. In untreated non-GCB DLBCL patients, the phase 3 PHOENIX study (Younes et al. J Clin Oncol. 2019;37:1285-95) showed that addition of the BTKi ibrutinib to R-CHOP (R-CHOP-I) did not improve outcomes in the intent-to-treat population. However, patients age <60y treated with R-CHOP-I had significantly improved progression-free survival (PFS) and overall survival (OS) compared with those receiving R-CHOP alone. Acalabrutinib is a second-generation BTKi with enhanced kinase selectivity and potential for better efficacy and tolerability than first-generation BTKis. There is a strong rationale for combining acalabrutinib with R-CHOP in patients with untreated DLBCL, and safety of acalabrutinib + R-CHOP has been shown in a phase 1b/2 study (Davies et al. ASH 2020).
Aims
To determine if the addition of acalabrutinib to R-CHOP leads to improved PFS in patients age ≤65y with untreated non-GCB DLBCL.
Methods
ESCALADE (ACE-LY-312; NCT04529772) is a phase 3, randomized, global, double-blind study of acalabrutinib vs placebo in combination with R-CHOP for treatment of newly diagnosed non-GCB DLBCL. The study is recruiting adults ≥18y and ≤65y with previously untreated DLBCL stage II–IV disease with a Revised International Prognostic Index (R-IPI) score of 2–5. Prior to randomization, all patients will receive an initial R‑CHOP cycle (cycle 1) as standard-of-care treatment to prevent delays in therapy initiation. Based on central Gene Expression Profile (GEP) testing performed after enrollment, patients with non-GCB DLBCL (activated B-cell like or unclassified) will be randomized into 2 arms to receive acalabrutinib 100 mg twice daily plus R-CHOP or placebo plus R-CHOP from cycle 2 to cycle 6 followed by 2 additional cycles of rituximab + acalabrutinib or placebo (cycles 7 and 8). All patients will receive primary prophylaxis with granulocyte colony-stimulating factors accompanying all R-CHOP cycles. The study aims to randomize 600 patients (~300 per arm). The primary objective is to evaluate whether the addition of acalabrutinib to R-CHOP will prolong PFS. Secondary endpoints include event-free survival, complete response rate, OS, pharmacokinetics, and safety. Key exclusion criteria are central nervous system involvement, primary mediastinal lymphoma, high-grade B-cell lymphoma, diagnosis or treatment of malignancy other than DLBCL, and history of indolent lymphoma. Approximately 250 sites globally will enroll patients. Enrollment began in Q3 of 2020.
Results
Trial in progress.
Conclusion
Study is currently recruiting.
Keyword(s): Diffuse large B cell lymphoma
Abstract: PB1434
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
R-CHOP remains the standard of care for DLBCL. Although most patients can be cured, 35–40% will experience relapsed/refractory disease, leading to poor outcomes in the majority of patients. Covalent irreversible Bruton tyrosine kinase inhibitors (BTKi) have shown higher responses in patients with non-GCB DLBCL than with GCB DLBCL. In untreated non-GCB DLBCL patients, the phase 3 PHOENIX study (Younes et al. J Clin Oncol. 2019;37:1285-95) showed that addition of the BTKi ibrutinib to R-CHOP (R-CHOP-I) did not improve outcomes in the intent-to-treat population. However, patients age <60y treated with R-CHOP-I had significantly improved progression-free survival (PFS) and overall survival (OS) compared with those receiving R-CHOP alone. Acalabrutinib is a second-generation BTKi with enhanced kinase selectivity and potential for better efficacy and tolerability than first-generation BTKis. There is a strong rationale for combining acalabrutinib with R-CHOP in patients with untreated DLBCL, and safety of acalabrutinib + R-CHOP has been shown in a phase 1b/2 study (Davies et al. ASH 2020).
Aims
To determine if the addition of acalabrutinib to R-CHOP leads to improved PFS in patients age ≤65y with untreated non-GCB DLBCL.
Methods
ESCALADE (ACE-LY-312; NCT04529772) is a phase 3, randomized, global, double-blind study of acalabrutinib vs placebo in combination with R-CHOP for treatment of newly diagnosed non-GCB DLBCL. The study is recruiting adults ≥18y and ≤65y with previously untreated DLBCL stage II–IV disease with a Revised International Prognostic Index (R-IPI) score of 2–5. Prior to randomization, all patients will receive an initial R‑CHOP cycle (cycle 1) as standard-of-care treatment to prevent delays in therapy initiation. Based on central Gene Expression Profile (GEP) testing performed after enrollment, patients with non-GCB DLBCL (activated B-cell like or unclassified) will be randomized into 2 arms to receive acalabrutinib 100 mg twice daily plus R-CHOP or placebo plus R-CHOP from cycle 2 to cycle 6 followed by 2 additional cycles of rituximab + acalabrutinib or placebo (cycles 7 and 8). All patients will receive primary prophylaxis with granulocyte colony-stimulating factors accompanying all R-CHOP cycles. The study aims to randomize 600 patients (~300 per arm). The primary objective is to evaluate whether the addition of acalabrutinib to R-CHOP will prolong PFS. Secondary endpoints include event-free survival, complete response rate, OS, pharmacokinetics, and safety. Key exclusion criteria are central nervous system involvement, primary mediastinal lymphoma, high-grade B-cell lymphoma, diagnosis or treatment of malignancy other than DLBCL, and history of indolent lymphoma. Approximately 250 sites globally will enroll patients. Enrollment began in Q3 of 2020.
Results
Trial in progress.
Conclusion
Study is currently recruiting.
Keyword(s): Diffuse large B cell lymphoma