AMPLIFY
AMPLIFY is the trial behind the first all-oral, fixed-duration CLL regimen approved in the US (February 2026): 14 cycles of two pills, then stop.
3-year PFS 76.5% (AV) and 83.1% (AVO) vs 66.5% (chemoimmunotherapy); AV PFS HR 0.65, AVO HR 0.42; OS favoured AV (HR 0.33) partly driven by COVID-19 deaths in the chemotherapy arm; uMRD higher with AVO. NEJM 2025. FDA approved acalabrutinib + venetoclax (without obinutuzumab) on 19 February 2026.
Setting
Fit, previously untreated CLL without del(17p)/TP53: fixed-duration acalabrutinib + venetoclax (AV) or + obinutuzumab (AVO) vs FCR/BR chemoimmunotherapy
Phase
Phase 3
Sponsor
AstraZeneca
Registry
Headline result
3-year PFS 76.5% (AV) / 83.1% (AVO) vs 66.5%.
Reported
2024
Enrolled
867
Replication
GLOW and CAPTIVATE (ibrutinib-venetoclax), CLL13 (venetoclax-obinutuzumab ± ibrutinib), and SEQUOIA arm D (zanubrutinib-venetoclax) all show BTKi + BCL2i fixed-duration efficacy; the class effect is robust across three BTK inhibitors.
In plain words
What these results mean for people, not percentages
Progression-free survival at 3 yearsprimarysurrogate endpoint
- 76.5 vs 83.1 out of 100 alive without the cancer growing at 3 years with Acalabrutinib + venetoclax compared with Acalabrutinib + venetoclax + obinutuzumab; 6.6 fewer per 100.
- On this measure the first group did worse, not better.
- Other groups: Chemoimmunotherapy (FCR/BR) 66.5 of 100.
Progression-free survival (AV vs CIT)surrogate endpoint
- The treated group had about 35 percent lower chance of the event at any given time (hazard ratio 0.65).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
Be careful
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Fit, previously untreated CLL without del(17p)/TP53: fixed-duration acalabrutinib + venetoclax (AV) or + obinutuzumab (AVO) vs FCR/BR chemoimmunotherapy. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (17p); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
867 participants enrolled.
Progression-free survival at 3 yearsprimary
Acalabrutinib + venetoclax76.5 of 100
n = 291
Acalabrutinib + venetoclax + obinutuzumab83.1 of 100
n = 286
Chemoimmunotherapy (FCR/BR)66.5 of 100
n = 290
Progression-free survival (AV vs CIT)
HR 0.65 (0.49–0.87)
Numbers not yet public.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival at 3 yearsprimary | Acalabrutinib + venetoclax | 291 | 76.5% | — | — | link |
| Acalabrutinib + venetoclax + obinutuzumab | 286 | 83.1% | ||||
| Chemoimmunotherapy (FCR/BR) | 290 | 66.5% | ||||
| Progression-free survival (AV vs CIT) | Acalabrutinib + venetoclax | — | — | 0.65 (0.49–0.87) | — | — |
| Chemoimmunotherapy | — | — |
Replication
GLOW and CAPTIVATE (ibrutinib-venetoclax), CLL13 (venetoclax-obinutuzumab ± ibrutinib), and SEQUOIA arm D (zanubrutinib-venetoclax) all show BTKi + BCL2i fixed-duration efficacy; the class effect is robust across three BTK inhibitors.