AMPLIFY: CALQUENCE®▼
(acalabrutinib) with venetoclax for
chronic lymphocytic leukaemia (CLL)

AMPLIFY: A Phase 3 trial of 14-month fixed-duration CALQUENCE + venetoclax ± obinutuzumab in 1L CLL²

AMPLIFY trial design^1,2,5,6

Study design

A randomised, open-label, multicentre Phase 3 study of CALQUENCE in combination with venetoclax with and without obinutuzumab compared with chemoimmunotherapy (FCR/BR) in patients with previously untreated CLL^1,2,6

• The trial included patients with certain risk features, such as uIGHV and bulky disease^1,2,6
• Patients with del(17p) and TP53 mutations respond poorly to standard chemoimmunotherapy and were therefore not included in the study^1,7,8

^*1 cycle=28 days (4 weeks or ~1 month).^2,4

^†50% of patients received FCR in the control arm (FCR/BR).¹

Study endpoints*

The primary endpoint in AMPLIFY was PFS (BICR-assessed) for CALQUENCE + venetoclax vs FCR/BR^2,3

2. Brown, J et al. N Engl J Med. 2025;392(8):748-762 and supplementary information; 3. Scientific Data on File Packet (sDoFP). February 12, 2025. REF-258959

*If primary endpoint met, secondary endpoints tested in fixed sequential hierarchy.¹

Stratification factors^1,2

• Age >65 vs ≤65 years
• IGHV mutated vs unmutated
• Rai stage ≥III vs <III
• Geographic region: North America vs Western Europe vs other

Eligibility criteria included:

Patient characteristics were generally well balanced across the AMPLIFY study arms^1,2*

Demographic and baseline characteristics^1,2

Adapted from Brown et al 2025.

Data are n (%) unless otherwise specified.

*Patients with del(17p) or TP53 mutations were not included in the study.^1,2

^†Europe includes Eastern and Western Europe; Other includes Argentina, Australia, Brazil, China, Korea, Saudi Arabia, South Africa, and Taiwan.^1,2

Superior PFS responses with CALQUENCE-based fixed-duration therapy vs FCR/BR at 3-year follow-up^1,2

77% of patients were estimated to be progression free at 40.8 months with CALQUENCE + venetoclax (HR=0.65; 95% CI: 0.49-0.87; P=0.0038 vs FCR/BR)^1,2

Primary endpoint: PFS for CALQUENCE + venetoclax vs FCR/BR^1,2

Adapted from Brown et al 2025.

ITT population.

Median follow-up from randomization: 40.8 months (range, 0–59 months). Hazard ratio (95% CI) computed using a Cox proportional-hazards model.

P-value based on stratified log-rank test.

PFS in the uIGHV Subgroup²

PFS assessed by IRC; PFS by IGHV status was a prespecified analysis (ITT population).

Hazard ratio (95% CI) computed using an unstratified Cox proportional-hazards model.

PFS in the mIGHV Subgroup²

PFS assessed by IRC; PFS by IGHV status was a prespecified analysis (ITT population).

Hazard ratio (95% CI) computed using an unstratified Cox proportional-hazards model.

PFS results for CALQUENCE-based fixed-duration therapy across all subgroups^1*

These PFS benefits were not statistically significant.

* Patients with del(17p) or TP53 mutations were not included in the study.¹

CALQUENCE + ventoclax showed a positive trend towards OS vs FCR/BR at 40.8 months median follow-up^1,2*

Estimated 3-year OS was 94% with CALQUENCE + venetoclax vs 86% with FCR/BR (HR=0.33; 95% CI: 0.18-0.56; P<0.001; not statistically significant due to secondary endpoints sequential hierarchy)^1,2*

OS for CALQUENCE + venetoclax vs FCR/BR^1,2

Adapted from Brown et al, 2025.

The OS data were immature (10% data maturity for CALQUENCE + venetoclax + obinutuzumab vs FCR/BR) at the time of analysis and can continue to change as more events occur. The trial will continue to assess OS as a key secondary endpoint.⁶

• CI widths have not been adjusted for multiplicity and may not be used in place of hypothesis testing¹

*Median follow-up from randomization: 40.8 months (range, 0–59 months). Hazard ratio (95% CI) computed using a Cox proportional-hazards model.

P-value based on stratified log-rank test.

93% ORR in patients with CALQUENCE-based fixed-duration therapy^1*

Secondary endpoint¹

Adapted from Brown et al, 2025.

OTHER is defined as CR with incomplete bone marrow recovery + nodular PR.¹

*Median follow-up from randomization: 40.8 months (range, 0–59 months).¹

89% of patients who received CALQUENCE + venetoclax did not require subsequent treatment at 3 years median follow-up^9*†‡

Time to next treatment (TTNT): Percent of patients not receiving subsequent therapy at 3 years⁹

TTNT was defined as the time from randomisation to institution of non-protocol–specified treatment for CLL or death⁹

*Calculation is based on the Kaplan-Meier technique.⁹

^†The CI for time to next anti-CLL therapy is derived based on Brookmeyer-Crowley method.⁹

^‡Median follow-up from randomization: 40.8 months (range, 0–59 months)

CALQUENCE + venetoclax demonstrates a safety profile consistent with the established tolerability of each agent^1-4

Common treatment-emergent AEs at 40.8 months median follow-up (Any Grade: ≥10%; Grade ≥3: ≥5%)^1,2

Adapted from Brown et al, 2025.

Data are n (%).

Table includes AEs occurring in ≥15% (any grade) or ≥5% (grade ≥3) of any treatment arm. AEs with an onset date or that worsened on or after the date of first dose and up to and including 30 days following the date of last dose of treatment or up to the day prior to start of subsequent anti-CLL therapy, whichever came first.²

CALQUENCE + venetoclax AEs of clinical interest were consistent with the established tolerability of each agent^1-4

AE’s of clinical interest at 40.8 months median follow-up^2*

Adapted from Brown et al, 2025.

Data are n (%). ECIs listed by category and sub-category.

*Median follow-up from randomization: 40.8 months (range, 0–59 months).1

^†Treatment duration was 14 months of CALQUENCE and 12 months of venetoclax; or 14 months of CALQUENCE, 12 months of venetoclax, and 6 months of obinutuzumab; or 6 months of FCR/BR.¹

^‡Ventricular tachyarrhythmias consisted of ventricular extrasystoles (n=1 in AV arm; n=2 in AVO arm) and ventricular tachycardia (n=1 each in AV and AVO arms).²

^§Grouping of preferred terms; defined as a haemorrhagic event that is serious, or Grade ≥3 in severity, or that is a CNS haemorrhage (any grade severity).6†Treatment duration was 14 months of CALQUENCE and 12 months of venetoclax; or 14 months of CALQUENCE, 12 months of venetoclax, and 6 months of obinutuzumab; or 6 months of FCR/BR.¹

^ǁIncludes neutropenia, neutrophil count decreased, and febrile neutropenia. AEs with an onset date or that worsen on or after the date of first dose and up to and including 30 days following the date of last dose of treatment or up to the day prior to start of subsequent anti-CLL therapy, whichever comes first.¹

Discontinuation rate of CALQUENCE + venetoclax due to AEs was low at 7.9% at 40.8 months median follow-up^1,2

Discontinuation rate of CALQUENCE due to any AEs^1,2*

*Median follow-up from randomization: 40.8 months (range, 0–59 months).¹

Please refer to the CALQUENCE SmPC for more information about Adverse Events.

Please refer to the Venetoclax and / or obinutuzumab SmPCs for further information about treatment related adverse events.