ELEVATE-TN: CALQUENCE▼ (acalabrutinib) with or without Obinutuzumab vs Chlorambucil and Obinutuzumab for chronic lymphocytic leukaemia (CLL)

ELEVATE-TN was an open-label, randomised, multicentre, pivotal Phase 3 study of
CALQUENCE (acalabrutinib) ± obinutuzumab (O) in patients with previously untreated CLL*¹
 

CALQUENCE SmPC Posology: The recommended dose is 100 mg CALQUENCE
twice daily (equivalent to a total daily dose of 200 mg).⁶

Refer to obinutuzumab prescribing information for recommended obinutuzumab
dosing information.^6,7

*As per inclusion/exclusion criteria in the ELEVATE-TN study.^1
†CALQUENCE + O: CALQUENCE 100 mg BID started on Day 1 of Cycle 1 until disease progression or unacceptable toxicity. O started on Cycle 2 (Day 1: 100 mg, Day 2: 900 mg, Day 8 and Day 15: 1000 mg each), followed by 1000 mg on Day 1 of Cycles 3 to 7. Each cycle was 28 days.^1
‡CALQUENCE monotherapy: 100 mg BID until disease progression or unacceptable toxicity.^1
ǁOClb: OClb was administered for a maximum of 6 cycles. O started on Cycle 1 (Day 1: 100 mg, Day 2: 900 mg, Day 8 and Day 15: 1000 mg each), followed by 1000 mg on Day 1 of Cycles 2 to 6. OClb 0.5 mg/kg was administered on both Days 1 and 15 of Cycles 1 to 6. Each cycle was 28 days.^1
§Statistical testing of secondary endpoints was planned in a fixed, sequential hierarchical manner. The study did not achieve statistical significance for IRC-assessed ORR between Calquence monotherapy and OCIb and therefore all P values for overall survival, if displayed, are considered descriptive in nature.

Endpoints in the ELEVATE-TN long-term follow-up

INV-assessed PFS in ITT population was a secondary endpoint
After the primary analysis, PFS was assessed by the investigators only.²
 

INV-assessed ORR in ITT population was a secondary endpoint
ORR was defined as achieving CR, CRi, nPR, or PR per the investigator or IRC assessment per iwCLL 2008 criteria at or before initiation of subsequent anticancer therapy.²
 

OS was a secondary endpoint
A total of 69 patients on OClb crossed over to CALQUENCE after confirmed disease progression.²
 

Statistical analysis
Hazard ratio for INV-assessed PFS in overall population was based on stratified Cox proportional hazards model and nominal P value was based on stratified log-rank test.²
 

Hazard ratio for INV-assessed PFS by del(17)(p13.1) and/or mutated TP53 status, and by IGHV mutation status, was based on unstratified Cox proportional hazards model and nominal P value was based on unstratified log-rank test.²

Key inclusion and exclusion criteria*¹

*As per inclusion/exclusion criteria in the ELEVATE-TN study. Not all inclusion/exclusion criteria have been included. For full details, please refer to the reference.
^†Calculated using the Cockcroft-Gault equation.
 

Patients in the OClb arm with IRC-confirmed disease progression were able to cross over to CALQUENCE monotherapy.¹
 

The trial met its primary endpoint at the data cut-off (8 February 2019) for the interim analysis.¹
At primary endpoint of IRC-assessed PFS, CALQUENCE demonstrated statistically significant superiority compared to standard of care OClb (P<0.0001); median follow-up 28.3 months; NR with CALQUENCE ± O vs 22.6 months (95% CI: 20.2-27.6) with OClb^1,3,4,6
 

Long-term results at median follow-up of 74.5 months are available.
Treatment still ongoing: Calquence + O 54%; Calquence 47%.⁴

CALQUENCE (acalabrutinib) was studied in a broad range of patients reflecting clinical practice

Patient characteristics were well balanced between treatment arms²

Adapted from Sharman JP, et al. Lancet. 2022 (Supplementary Appendix).

Durable PFS with CALQUENCE (acalabrutinib) ~6-year follow-up data^3,4

INV PFS (overall study population) was an exploratory objective^2-4

62% of previously untreated CLL patients receiving CALQUENCE (acalabrutinib) monotherapy were progression-free at ~6 years^3,4

Adapted from Sharman JP et al. Lancet 2020¹; Sharman JP, et al. Leukaemia 2022²; Sharman JP, et al. Presented at the American Society of Haematology (ASH) Annual Meeting; December 9-12, 2023. Presentation #6364; Sharman JP, et al. (ASCO) Annual Meeting; June 3-7, 2022⁸

*Both HRs are compared with the OClb arm.^4
⸸HR based on stratified cox proportional- hazards model. P-value based on stratified log-rank test and is descriptive only.Independent review committee (IRC) PFS was outlined as a secondary endpoint in the 24 month ELEVATE-TN data cut off protocol, however in later data follow ups, investigator (INV) assessed PFS was outlined as an exploratory endpoint.^1,2

At the time of analysis, median OS was not reached in any group^1-3

OS/ORR results after a median follow-up of 28.3 months at interim analysis¹ and 74.5 months in the long-term follow-up^3,4
 

Adapted from Sharman JP et al. Lancet 2020¹, Sharman JP et al. Blood 2023³, and Sharman JP, et al.  Presented at the American Society of Haematology (ASH) Annual Meeting; December 9-12, 2023. Presentation #6364

*HR based on stratified cox proportional- hazards model. P-value based on stratified log-rank test and is descriptive only.^2,3
Independent review committee (IRC) PFS was outlined as a secondary endpoint in the 24 month ELEVATE-TN data cut off protocol, however in later data follow ups, investigator (INV) assessed PFS was outlined as an exploratory endpoint¹

44.6% of patients in the OClb arm crossed over to CALQUENCE monotherapy due to disease progression¹

Consistent improvement in PFS with CALQUENCE (acalabrutinib) vs OClb across exploratory high-risk subgroups^1,2,9

British Society for Haematology (BSH) Guidelines state that CALQUENCE is one of the preferred treatment options for eligible patients with TP53 disruption.¹⁰
No difference in PFS vs the ITT population, regardless of high-risk genomic features (comprising patients with unmutated or mutated IGHV, and those with del(17p) and/or mutated TP53)⁹

Exploratory Analysis: PFS in patients with del(17p) and/or TP53 status at ~6 year follow-up⁴
 

Adapted from Sharman J, et al. Presented at: American Society of Hematology (ASH); 9-12 December 2023. Presentation #6364

Exploratory Analysis: INV PFS in patients with unmutated and mutated IGHV at ~6 year follow-up⁴
 

Adapted from Sharman J, et al. Presented at: American Society of Hematology (ASH); 9-12 December 2023. Presentation #636⁴

Median follow-up times: Calquence + O 74.6 months, Calquence mono 74.5 months, OClb 73.3 months⁴
*Hazard ratio was based on unsatisfied Cox proportional hazards model
^ꝉP-values based on unstratified log-rank test and are descriptive only⁴

Safety and tolerability in ELEVATE-TN were consistent with the known profile of CALQUENCE (acalabrutinib)^2,9

Most common AEs (≥10%) in the ELEVATE-TN study*¹

Adapted from Sharman P, et al. Lancet 2020

Median follow-up: 28.3 months¹
Incidence of ARs    ■≥10% ■<10% - ≥1% ■<1%

*As per inclusion and exclusion criteria in the ELEVATE-TN study¹.
†One patient initially allocated to CALQUENCE + O only received CALQUENCE monotherapy. One patient withdrew consent from the CALQUENCE monotherapy arm¹.

Selected events of clinical interest at ~6 year long-term follow-up^3,4

CALQUENCE was generally well tolerated for the duration of long-term follow-up. Events of clinical interest were similar in both CALQUENCE containing arms and consistent with previous results.⁴
Treatment was ongoing for 47% of patients on Calquence monotherapy at 74.5 month median follow-up.³

Adapted from Sharman J, et al. Presented at: American Society of Hematology (ASH); 9-12 December 2023. Presentation #6364

Median follow-up: 74.5 months⁴

Data are No. (%) unless otherwise specified⁴

*Hypertension events were based on Standardized MedDRA query (SMQ) Hypertension (narrow)⁴