Phase 3 randomized double-blind study of abemaciclib (Verzenio, CDK4/6 inhibitor) vs placebo in advanced dedifferentiated liposarcoma (DDLPS) — a rare, aggressive sarcoma subtype driven by CDK4 amplification. Presented as ASCO 2026 Plenary (LBA2) by Mark A. Dickson, MD (Memorial Sloan Kettering). Median PFS 9.7 vs 1.5 months (HR 0.38) — the first positive Phase 3 trial in DDLPS, a disease with no currently approved systemic therapy.
Slides shared by KOLs at ASCO 2026 Plenary (presented by Mark A. Dickson, MD — MSK). Click any image to expand.
New · ASCO 2026 Plenary Readout
SARC041 primary results presented May 31, 2026 (Mark A. Dickson, MD). Abemaciclib significantly improved PFS vs placebo in advanced dedifferentiated liposarcoma — median PFS 9.7 vs 1.5 months, HR 0.38 (90% CI 0.25–0.59), p<0.001. A positive OS trend favored abemaciclib despite 85% placebo crossover (median OS not reached vs 25.5 months; HR 0.55, p=0.07). The first positive Phase 3 trial in DDLPS. The KOL slide decks below capture the primary PFS, OS, schema, and conclusions slides.
[Slide 1]
Schema
Advanced / metastatic Dedifferentiated Liposarcoma
Stratify by:
Prior systemic treatment (0 vs ≥1)
Randomization 1:1
Abemaciclib
Placebo
CT q6w X 36w
200 mg PO bid
crossover
200 mg PO bid
then q12w
ASCO
PRESENTED BY: Mark A. Dickson, MD
#ASCO26
ASCO
AMERA
CLINIC
MEETING
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KNOWLEDGE CONQU
---
[Slide 2]
Progression-Free Survival
Primary endpoint
placebo
abemaciclib
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
abemaciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
26 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY OF
NUAL MEETING
CLINICAL ONCOLOGY
Presentation is property of the author and ASCO. Permission required for reuse: contact permissions@asco.org.
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
Progression-Free Survival after Crossover
All
1.00
46 patients (85%)
received abemaciclib
Probability of PFS
0.75
after crossover
after progression on
placebo
0.50
Median PFS after
0.25
crossover to
0.00
abemaciclib:
0
10
20
30
3.4 months
Months from crossover
Number at risk
Response rate: 4%
All
46
7
1
1
0
10
20
30
Months from crossover
026 ASCO
PRESENTED BY: Mark A. Dickson, MD
#ASCO26
ASCO
AMERICAN SOCIETY OF
CLINICAL ONCOLOGY
NNUAL MEETING
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---
[Slide 4]
Overall Survival
placebo
abemaciclib
Median OS
abemaciclib: Not reached
1.00
placebo: 25.5 months
Overall survival probability
0.75
Hazard ratio 0.55
0.50
(95% Cl: 0.28-1.07)
Stratified log-rank
0.25
p-value: 0.07
12-month OS
abemaciclib: 85%
0.00
placebo: 71%
0
10
20
30
40
50
Months from randomization
24-month OS
abemaciclib: 72%
Number at risk
placebo: 51%
placebo
54
34
20
8
1
0
abemaciclib
54
34
22
9
4
0
0
10
20
30
40
50
Months from randomization
2026 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY OF
ANNUAL MEETING
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CLINICAL ONCOLOGY
KNOWLEDGE CONQUERS CANCER
[Slide 1]
Schema
Advanced / metastatic Dedifferentiated Liposarcoma
Stratify by:
Prior systemic treatment (0 vs ≥1)
Randomization 1:1
Abemaciclib
Placebo
CT q6w X 36w
200 mg PO bid
200 mg PO bid
crossover
then q12w
2026 ASCO
PRESENTED
BY: Mark A. Dickson, MD
#ASCO26
ASCO
AMERICAN SOCIETY OF
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse: contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 2]
Progression-Free Survival
placebo
abemaciclib
Primary endpoint
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
abemaciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
2026 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY Of
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
Overall Survival
placebo
abemaciclib
Median OS
abemaciclib: Not reached
1.00
placebo: 25.5 months
Overall survival probability
0.75
Hazard ratio 0.55
(95% Cl: 0.28-1.07)
0.50
Stratified log-rank
0.25
p-value: 0.07
12-month OS
abemaciclib: 85%
0.00
placebo: 71%
0
10
20
30
40
50
24-month OS
Months from randomization
abemaciclib: 72%
Number at risk
placebo: 51%
placebo
54
34
20
8
1
0
abemaciclib
54
34
22
9
4
0
0
10
20
30
40
50
Months from randomization
2026 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY OF
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 4]
Conclusions
First positive clinical trial in dedifferentiated
liposarcoma
PFS was significantly improved with
abemaciclib VS placebo
Even though most patients in the placebo group
crossed over to receive abemaciclib, a positive
SARC041 Patient Summary
overall survival trend favored the abemaciclib
group
Abemaciclib was well-tolerated
2026 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY OF
CLINICAL ONCOLOGY
ANNUAL MEETING
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KNOWLEDGE CONQUERS CANCER
[Slide 1]
SARC041: A Phase 3 Randomized Double-Blind Study
of Abemaciclib versus Placebo in Patients with
Advanced Dedifferentiated Liposarcoma
Mark A. Dickson, Karla V. Ballman, Mia Weiss, Steven Attia, Michael J. Wagner,
Seth Pollack, Edwin Choy, Andrew J. Wagner, Breelyn Wilky, Lara E. Davis,
Richard F. Riedel, Andrew Koff, William D. Tap
Memorial Sloan Kettering Cancer Center, Mayo Clinic, Washington University School of
Medicine, Dana-Farber Cancer Institute, Northwestern University, Mass General Brigham
Cancer Institute, University of Colorado Anschutz Cancer Center, Fred Hutchinson Cancer
Center, Duke Cancer Institute, Weill Cornell Medical College
2026 ASCO
PRESENTS in Mark A. Dickson, MD
#ASCO26
ASCO
DATE
ANNUAL MEETING
- powerly who at NCS - - x
- - CANCER
---
[Slide 2]
Progression-Free Survival
placebo
abemaciclib
Primary endpoint
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
2026ASCO
ANNUAL MEETING
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
abemaciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
2026 ASCO
PRESENTED BY) Mark A. Dickson, MD
#ASCO26
ASCO
-
-
INCOUDER
ANNUAL MEETING
I
I
of
the
author
and
ASCO
Permission
request
for
I
contact
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
Overall Survival
placebo
abemaciclib
Median OS
abemaciclib: Not reached
1.00
placebo: 25.5 months
Overall survival probability
0.75
Hazard ratio 0.55
(95% Cl: 0.28-1.07)
0.50
Stratified log-rank
0.25
p-value: 0.07
12-month OS
2026
ASCO
abemaciclib: 85%
ANNUAL MEETING
placebo: 71%
0.00
0
10
20
30
40
50
24-month OS
Months from randomization
abemaciclib: 72%
Number at risk
placebo: 51%
placebo
54
34
20
8
1
0
maciclib
54
34
22
9
4
0
0
10
20
30
40
50
Months from randomization
ASCO
#ASCO26
PRE SENTED on Mark A. Dickson, MD
ASCO
AMERICAN
CURRENT encouper
MEETING
Presentation poperty of the - and ASCO Permission - for - contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 4]
16
Progression-Free Survival (Abemaciclib Only)
no prior lines of therapy
1 or more prior lines of therapy
Exploratory Analysis
1.00
by Prior Therapy
0.75
Log-rank
Median PFS
0.50
p = 0.029
0.25
No prior lines of therapy:
16.4 months
0.00
0
6
12
18
24
30
36
42
Months from randomization
One or more prior lines of
Progression-Free Survival (Abemaciclib Only)
therapy:
0 prior
27
16
12
8
6
2
1
0
5.3 months
21 prior
27
11
5
3
2
1
1
1
0
6
12
18
24
30
36
42
Months from randomization
2026 ASCO
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY or
#ASCO26
CUNICAL OHCOLOGY
ANNUAL MEETING
Presentation . property of the author and ASCO Permission required for - contact permissions@asce.org permissions PS
KNOWLEDGE CONQUERS CANCER
[Slide 1]
Schema
Advanced / metastatic Dedifferentiated Liposarcoma
Stratify by:
Prior systemic treatment (0 vs ≥1)
Randomization 1:1
Abemaciclib
Placebo
CT q6w X 36w
200 mg PO bid
200 mg PO bid
crossover
then q12w
2026 ASCO
PRESENTED
BY: Mark A. Dickson, MD
#ASCO26
ASCO
AMERICAN SOCIETY or
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 2]
Progression-Free Survival
placebo
abemaciclib
Primary endpoint
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
abemaciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
2026 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY or
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
16
Progression-Free Survival (Abemaciclib Only)
no prior lines of therapy
1 or more prior lines of therapy
Exploratory Analysis
1.00
by Prior Therapy
0.75
Log-rank
Median PFS
0.50
p = 0.029
0.25
No prior lines of therapy:
16.4 months
0.00
0
6
12
18
24
30
36
42
Months from randomization
One or more prior lines of
Progression-Free Survival (Abemaciclib Only)
therapy:
0 prior
27
16
12
8
6
2
1
0
5.3 months
>1 prior
27
11
5
3
2
1
1
1
0
6
12
18
24
30
36
42
Months from randomization
2026 ASCO
#ASCO26
PRE
SENTED
=
BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY
CUNICAL ONCOLOGY
ANNUAL MEETING
Presentation - property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 4]
CDK4 amplification drives Dedifferentiated Liposarcoma
High level amplification of CDK4 in nearly all tumors
CDK4 inhibitors are active in vitro and in vivo
Two phase 2 clinical trials of palbociclib in DDLS: mPFS 4.2 months
Phase 2 clinical trial of abemaciclib in DDLS: mPFS 7.7 months
Abemaciclib is the most CDK4 selective inhibitor available
Barretina et al., Nat Genet 2010
Zhang et al. Mol Cancer Ther 2014
Dickson et al. JCO 2013
Dickson et al. JAMA Oncol. 2016
Gleason et al. Clin Cancer Res. 2024
2026 ASCO
#ASCO26
PRS SENTED M -
Mark A. Dickson, MD
ASCO
- OF
CUNICAL DRODUCT
ANNUAL MEETING
Proventation - property - - - and ASCO Permission required for - -
KNOWLEDGE CONQUERS CANCER
[Slide 1]
Conclusions
First positive clinical trial in dedifferentiated
liposarcoma
PFS was significantly improved with
abemaciclib vs placebo
Even though most patients in the placebo group
crossed over to receive abemaciclib, a positive
SARC041 Patient Summary
overall survival trend favored the abemaciclib
group
Abemaciclib was well-tolerated
2026 ASCO
I
SENTED
$
#ASCO26
Mark A. Dickson, MD
ASCO
- ROCIETY or
CLINICAL
ANNUAL MEETING
Presentation in property - - - and ASCO Permission required - - contact
KNOWLEDGE CONQUERS CANCER
---
[Slide 2]
Progression-Free Survival
placebo
abemaciclib
Primary endpoint
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
abemaciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
ASCO
PMS
MONTED
#ASCO26
1
Mark A Dickson, MD
ASCO
ORICAL -
INUAL MEETING
- property of - - and ASCO Permission required - - -
KNOWLEDGE CONQUERS c CANCER
---
[Slide 3]
CDK4 amplification drives Dedifferentiated Liposarcoma
High level amplification of CDK4 in nearly all tumors
CDK4 inhibitors are active in vitro and in vivo
Two phase 2 clinical trials of palbociclib in DDLS: mPFS 4.2 months
Phase 2 clinical trial of abemaciclib in DDLS: mPFS 7.7 months
Abemaciclib is the most CDK4 selective inhibitor available
Barretina et al., Nat Genet 2010
Zhang et al. Mol Cancer Ther 2014
Dickson et al. JCO 2013
Dickson et al. JAMA Oncol. 2016
Gleason et al. Clin Cancer Res. 2024
2026 ASCO
#ASCO26
PRS SENTED M BY
Mark A. Dickson, MD
ASCO
- OF
CURRICAL -
ANNUAL MEETING
Provention - priparty - Fire wher and ASCO Permission regist for - contact
KNOWLEDGE CONQUERS CANCER
[Slide 1]
Progression-Free Survival
placebo
abemaciclib
Primary endpoint
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
0.50
placebo: 1.5 months
0.25
Hazard ratio 0.38
(90% Cl: 0.25-0.59, P <0.001)
0.00
6-month PFS
0
10
20
30
40
Months from randomization
abemaciclib: 60%
placebo: 22%
Number at risk
placebo
54
12-month PFS
8
3
0
0
abemaciclib
54
21
abemaciclib: 39%
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
2026 ASCO
PRESENTED T. Mark A. Dickson, MD
ASCO
addition
#ASCO26
LINES -
ANNUAL MEETING
Presentation $ property of be author and ASCO Permission agent or
KNOWLEDGE CONDUCTS CARCER
---
[Slide 2]
Conclusions
First positive clinical trial in dedifferentiated
liposarcoma
PFS was significantly improved with
abemaciclib VS placebo
Even though most patients in the placebo group
crossed over to receive abemaciclib, a positive
overall survival trend favored the abemaciclib
group
Abemaciclib was well-tolerated
2026 ASCO
PRESENTED BY: Mark A. Dickson, MD
#ASCO26
ANNUAL MEETING
Presentation is property of the author and ASCO. Permission required for reuse: contact permissions@asco.org.
[Slide 1]
Schema
Advanced / metastatic Dedifferentiated Liposarcoma
Stratify by:
Prior systemic treatment (0 vs ≥1)
Randomization 1:1
Abemaciclib
Placebo
CT q6w X 36w
200 mg PO bid
200 mg PO bid
then q12w
crossover
2026 ASCO
PRE SENTED BY:
Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY or
#ASCO26
CURICAL DIVCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse: contact permissions@asoo.org.
KNOWLEDGE CONQUERS CANCER
---
[Slide 2]
Progression-Free Survival
Primary endpoint
placebo
abemaciclib
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
maciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
SCO
PRESENTED BY: Mark A. Dickson, MD
#ASCO26
ASCO
AMERICAN SOCETVOR
CUNICAL ONCOLOGY
MEETING
Presentation is property of the author and ASCO Permission required for reuse: contact permissions@asce.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
Overall Survival
placebo
abemaciclib
Median OS
abemaciclib: Not reached
1.00
placebo: 25.5 months
Overall survival probability
0.75
Hazard ratio 0.55
(95% Cl: 0.28-1.07)
0.50
Stratified log-rank
12-month OS
0.25
p-value: 0.07
abemaciclib: 85%
placebo: 71%
0.00
0
10
20
30
40
50
24-month OS
Months from randomization
abemaciclib: 72%
Number at risk
placebo: 51%
placebo
54
34
20
8
1
0
bemaciclib
54
34
22
9
4
0
0
10
20
30
40
50
Months from randomization
ASCO
PRE SENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY or
#ASCO26
CURICAL ONCOLOGY
IUAL MEETING
Presentation 6 property of the author and ASCO Pennission required for reuse, contact permissions@asce.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 4]
Phase 3 trial results for Dedifferentiated Liposarcoma
Progression
Difference in
Line
required
mPFS
mPFS
Outcome
Ref
eribulin VS dacarbazine
3rd Line
no
2.0m VS 2.1m
0.1 month
FDA-approved
Demetri et al. JCO 2017
trabectedin vs dacarbazine
2-3rd Line
no
2.2m VS 1.9m
0.3 month
FDA-approved
Patel et al. Cancer 2019
3rd Line
selinexor vs placebo
yes
2.8m vs 2.1m
0.7 month
negative
Gounder et al., JCO 2022
milademetan vs trabectedin
2nd Line
yes
3.6m vs 2.2m
1.4 months
negative
Sanfilippo et al., CTOS 2023
brigimadlin vs doxorubicin
1st Line
no
8.4m vs 7.2m
1.2 months
negative
Schöffski et al., CTOS 2024
abemaciclib vs placebo
Any Line
yes
9.7m vs 1.5m
8.2 months
positive
Dickson et al., ASCO 2026
ASCO
PRE SENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCETY OF
#ASCO26
CUINICAL GHICOLOGY
NNUAL MEETING
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KNOWLEDGE CONQUERS CANCER
[Slide 1]
Schema
Advanced / metastatic Dedifferentiated Liposarcoma
Stratify by:
Prior systemic treatment (0 vs ≥1)
Randomization 1:1
Abemaciclib
Placebo
CT q6w X 36w
200 mg PO bid
200 mg PO bid
crossover
then q12w
2026 ASCO
PRESENTED
BY: Mark A. Dickson, MD
#ASCO26
ASCO
AMERICAN SOCIETY or
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 2]
Progression-Free Survival
placebo
abemaciclib
Primary endpoint
1.00
Stratified log-rank
Median PFS
0.75
p-value: <0.001
abemaciclib: 9.7 months
placebo: 1.5 months
0.50
Hazard ratio 0.38
0.25
(90% Cl: 0.25-0.59, p <0.001)
0.00
6-month PFS
0
10
20
30
40
abemaciclib: 60%
Months from randomization
placebo: 22%
Number at risk
12-month PFS
placebo
54
8
3
0
0
abemaciclib: 39%
abemaciclib
54
21
9
3
2
placebo: 13%
0
10
20
30
40
Months from randomization
2026 ASCO
#ASCO26
PRESENTED BY: Mark A. Dickson, MD
ASCO
AMERICAN SOCIETY or
CLINICAL ONCOLOGY
ANNUAL MEETING
Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
16
Progression-Free Survival (Abemaciclib Only)
no prior lines of therapy
1 or more prior lines of therapy
Exploratory Analysis
1.00
by Prior Therapy
0.75
Log-rank
Median PFS
0.50
p = 0.029
0.25
No prior lines of therapy:
16.4 months
0.00
0
6
12
18
24
30
36
42
Months from randomization
One or more prior lines of
Progression-Free Survival (Abemaciclib Only)
therapy:
0 prior
27
16
12
8
6
2
1
0
5.3 months
21 prior
27
11
5
3
2
1
1
1
0
6
12
18
24
30
36
42
Months from randomization
2026 ASCO
#ASCO26
PRE SENTED BY: Mark A. Dickson, MD
ASCO
SOCIETY C
CUNICAL ONCOLOGY
ANNUAL MEETING
Presentation " property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
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[Slide 4]
CDK4 amplification drives Dedifferentiated Liposarcoma
High level amplification of CDK4 in nearly all tumors
CDK4 inhibitors are active in vitro and in vivo
Two phase 2 clinical trials of palbociclib in DDLS: mPFS 4.2 months
Phase 2 clinical trial of abemaciclib in DDLS: mPFS 7.7 months
Abemaciclib is the most CDK4 selective inhibitor available
Barretina et al., Nat Genet 2010
Zhang et al. Mol Cancer Ther 2014
Dickson et al. JCO 2013
Dickson et al. JAMA Oncol. 2016
Gleason et al. Clin Cancer Res. 2024
2026 ASCO
#ASCO26
PRS SENTED BY
Mark A. Dickson, MD
ASCO
- OF
CUNICAL DRODUCT
ANNUAL MEETING
Proventation - priparty - - - and ASCO Permission required for - -
KNOWLEDGE CONQUERS CANCER
SARC041 (NCT04967521) is a SARC-sponsored, Lilly-funded, investigator-initiated Phase 3 randomized double-blind study of the CDK4/6 inhibitor abemaciclib (Verzenio) versus placebo in patients with advanced (locally recurrent and/or metastatic) dedifferentiated liposarcoma (DDLPS). DDLPS is a rare, aggressive soft-tissue sarcoma subtype with limited systemic therapy options. The biological rationale rests on near-universal CDK4 amplification in DDLPS — making selective CDK4 inhibition a precision-targeted strategy. Patients with placebo-arm progression cross over to open-label abemaciclib. Principal investigator: Mark A. Dickson, MD (Memorial Sloan Kettering). Presented as an ASCO 2026 Plenary Session presentation (LBA2) on Sunday, May 31, 2026.
Study Design
Phase 3 randomized double-blind multicenter U.S. study. 108 patients enrolled across 9 SARC-network centers (powered at 80% / two-sided alpha 10% to detect HR 0.6). Crossover to open-label abemaciclib permitted at progression.
Population
Adults (≥18) with histologically confirmed locally recurrent and/or metastatic dedifferentiated liposarcoma. ECOG PS 0-1. RECIST 1.1 measurable disease with documented progression (new disease, new sites, or ≥20% growth within 6 months of registration).
Primary: Progression-free survival (PFS) by investigator-assessed RECIST 1.1. Secondary: Objective response rate (ORR), PFS and ORR after crossover, overall survival (OS), safety. Exploratory: Archival tissue biomarkers.
Efficacy & Safety
SARC041 Plenary Results
INVESTIGATIONAL · DDLPSAbemaciclib is FDA-approved in HR+/HER2- breast cancer but remains investigational for dedifferentiated liposarcoma
SARC041 is the first positive Phase 3 study of a CDK4/6 inhibitor in dedifferentiated liposarcoma. Eli Lilly has indicated the data will support a regulatory submission for a new DDLPS indication. KOL reaction at the Plenary was strongly positive — characterized as practice-changing for a disease with virtually no effective systemic options.
Progression-Free Survival (Primary Endpoint)
Abemaciclib met the primary endpoint with a median PFS of 9.7 months versus 1.5 months for placebo — hazard ratio 0.38 (90% CI 0.25–0.59), stratified log-rank p<0.001. The benefit held across landmark timepoints: 6-month PFS 60% vs 22% and 12-month PFS 39% vs 13%. This is the first positive Phase 3 readout for any systemic therapy in dedifferentiated liposarcoma. An exploratory analysis by prior treatment showed a larger effect in treatment-naive patients (median PFS 16.4 months with no prior lines vs 5.3 months with ≥1 prior line; p=0.029).
A positive OS trend favored abemaciclib despite 85% of placebo patients crossing over to open-label abemaciclib at progression. Median OS was not reached with abemaciclib versus 25.5 months for placebo — HR 0.55 (95% CI 0.28–1.07), stratified log-rank p=0.07. Landmark OS favored abemaciclib at 12 months (85% vs 71%) and 24 months (72% vs 51%). The OS comparison did not cross the significance threshold — expected given the high crossover — but the consistent direction reinforces the PFS benefit.
Objective response rate was 9% with abemaciclib versus 0% with placebo, consistent with abemaciclib's distinction as the only CDK4/6 inhibitor producing meaningful monotherapy responses in DDLPS (a disease dominated by disease stabilization rather than tumor shrinkage). Among the 46 placebo patients (85%) who crossed over to abemaciclib at progression, post-crossover median PFS was 3.4 months with a 4% response rate — demonstrating activity even in a more heavily pretreated, progressing population.
Dedifferentiated liposarcoma most commonly arises in the retroperitoneum or abdomen. Recurrent/metastatic disease has historically had no standard-of-care systemic therapy — chemotherapy provides modest, short-lived benefit, and prior CDK4/6i trials (palbociclib, ribociclib) showed primarily stable disease. The earlier Phase 2 abemaciclib monotherapy study (Dickson et al., 30 patients) reported median PFS of 30-33 weeks and 12-week PFS of 76.7%, providing the rationale for SARC041.
Abemaciclib is an oral selective CDK4/6 inhibitor (vs the broader CDK4/6 class — palbociclib, ribociclib). DDLPS is characterized by amplification of the 12q13-15 region containing CDK4 and MDM2, making CDK4 a near-universal oncogenic driver. Inhibition disrupts cell-cycle progression and, per correlative work, induces tumor-cell senescence with secondary immune infiltration (CD4+ TILs). Among the three approved CDK4/6 inhibitors, abemaciclib is unique in producing meaningful monotherapy objective responses.
The Plenary safety profile was consistent with the well-characterized abemaciclib class effects from monarchE (adjuvant breast) and MONARCH 2/3 (metastatic breast): predominantly low-grade diarrhea, neutropenia, and fatigue. Grade ≥3 neutropenia rate in prior abemaciclib monotherapy trials runs in the 20-25% range, with median time-to-onset ~29-37 days; dose reduction to 100 mg has not historically compromised efficacy. No new safety signals were reported in the earlier DDLPS Phase 2. Full DDLPS-specific safety detail is in the Plenary deck and the upcoming publication.
Verzenio (abemaciclib) is currently approved by FDA in HR+/HER2- early and metastatic breast cancer. SARC041 provides the first randomized Phase 3 evidence of a CDK4/6 inhibitor benefit in any sarcoma subtype. Eli Lilly has stated the SARC041 data will support a regulatory submission for an expanded DDLPS indication. The Plenary selection (LBA2) — alongside LIBRETTO-432, HARMONi-6, RASolute 302, and PROTEUS — signals ASCO's view of the study as practice-changing for a rare disease with no current standard of care.
