Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
Thursday, September 30, 2021
TPD DIGEST:September 2021ESMO Congress Post-Conference ReportCopyright: Hanson Wade 2021
This Digest has been created through considerable effort by Hanson Wade’s Beacon TPD research team. The terms of subscription restrict usage of this work to those who are named subscribers to the service. Unauthorized copying and/or distribution of this document constitutes copyright infringement. If you are in doubt about whether you are entitled to receive a copy of this Digest, check with your account holder or with Hanson Wade ([email protected])
www.beacon-intelligence.com
Welcome
• Earlier this month the European Society for Medical Oncology (ESMO) held their annual congress.
• In total, 23 abstracts were presented which are associated with a trial on Beacon TPD.
• This month’s digest provides an analysis of these abstracts, looking at the type of data presented.
• The analysis is followed by the summaries of all abstracts, grouped by clinical data and trial outlines, with links to the
relevant Beacon pages.
Table of Contents
• Monthly Updates
• Abstract Analysis
• Trial Data and Outlines
• Summary & Coming Up
Welcome to September
www.beacon-intelligence.com
Phase Distribution
Monthly Updates: Trials Added
1
5
1
4
3
2
0
1
2
3
4
5
6
Early Phase I Phase 1 Phase 1/2 Phase 2 Phase 3 Phase Unknown
Nu
mb
er
of T
ria
ls
www.beacon-intelligence.com
Therapeutic Class Distribution
Monthly Updates: Trials Added
9
4
3
1 1 1
0
1
2
3
4
5
6
7
8
9
10
IMiD SERD Proteasome Inhibitor E3 Modulator Bivalent Degrader Protein Degrader
Nu
mb
er
of T
ria
ls
www.beacon-intelligence.com
Table of Trials Added
Monthly Updates: Trials Added
Trial ID Phase Sponsor Disease Indication Drug Names
ChiCTR2100050786
Early
Phase 1 The Affiliated Hospital of Xuzhou Medical University
B-Cell Lymphoma, Central Nervous System
Lymphoma Lenalidomide
NCT04951778 1 Celgene
Myelodysplastic Syndrome, Acute Myeloid
Leukemia CC-91633
NCT05050097 1 Janssen Research & Development, LLC Multiple Myeloma
Lenalidomide,
Pomalidomide,
Carfilzomib
HWID39189 1 Accutar Biotechnology Inc Breast Cancer AC0682
2020-003178-34 1 Aileron Therapeutics Healthy Volunteers ALRN-6924
NCT05052970 1 CSPC ZhongQi Pharmaceutical Technology Co. Multiple Myeloma Bortezomib
NCT05054374 1/2 Memorial Sloan-Kettering Cancer Center Breast Cancer, Solid Tumors Fulvestrant
NCT05032820 2 Medical College of Wisconsin Multiple Myeloma Lenalidomide
NCT05050305 2 Dana-Farber Cancer Institute Multiple Myeloma, CNS Tumors
Pomalidomide,
Marizomib
NCT05050630 2 Affiliated Hospital to Academy of Military Medical Sciences
Hodgkin Lymphoma, Non-Hodgkin
lymphoma, High Grade B-cell Lymphoma,
Diffuse Large B-Cell Lymphoma Lenalidomide
ChiCTR2100051262 2 Changzhou Pharmaceutical Factory Advanced Colorectal Cancer Thalidomide
CTR20212307 3 Sihuan Pharmaceutical Holdings Group, XuanZhu Pharma Co Ltd Breast Cancer Fulvestrant
NCT05028348 3 European Myeloma Network Multiple Myeloma Pomalidomide
NCT05038735 3 Novartis Pharmaceuticals Breast Cancer Fulvestrant
NCT05047848 U Liaoning Tumor Hospital & Institute Breast Cancer Fulvestrant
NCT05058755 U
Xinhua Hospital affiliated to Shanghai Jiaotong University, School
of Medicine Extranodal NK/T- cell lymphoma Lenalidomide
www.beacon-intelligence.com
Phase Distribution
Monthly Updates: Trials Updates
1
41
25
64
42
31
0
10
20
30
40
50
60
70
Early Phase 1 Phase 1 Phase 1/2 Phase 2 Phase 3 Phase 4 Phase Unknown
Nu
mb
er
of T
ria
ls
www.beacon-intelligence.com
Recruitment Status Distribution
Monthly Updates: Trials Updates
67
62
22
15
4 42 1
0
10
20
30
40
50
60
70
80
Recruitingparticipants
Active notrecruiting
Completed Not yet recruiting Terminated Unknown Suspended Enrolling byinvitation
Nu
mb
er
of T
ria
ls
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT04065555 Early Phase 1 Recruiting participants Presage Biosciences
NCT01877382 1 Active not recruiting Daiichi Sankyo, Inc.
NCT04895410 1 Recruiting participants Abbvie
NCT03432741 1 Recruiting participants Mayo clinic
NCT02942095 1 Active not recruiting M.D. Anderson Cancer Center
NCT03269136 1 Active not recruiting Pfizer
NCT03449381 1 Recruiting participants Boehringer Ingelheim
NCT04242953 1 Recruiting participants Sun Pharma Advanced Research Company (SPARC)
NCT02734615 1 Active not recruiting Novartis Pharmaceuticals
NCT04956302 1 Not yet recruiting Ohio State University Comprehensive Cancer Center
NCT01965353 1 Completed Dana-Farber Cancer Institute
NCT04247126 1 Recruiting participants Syros Pharmaceuticals
ACTRN12613000283774 1 Terminated Celgene, The Alfred Hospital
NCT02513186 1 Active not recruiting Sanofi
NCT04912427 1 Not yet recruiting Washington University School of Medicine
NCT02333370 1 Active not recruiting Novartis Pharmaceuticals
NCT01661400 1 Recruiting participants Washington University School of Medicine
NCT03767335 1 Recruiting participants Menarini Group
NCT04940026 1 Completed Sanofi
NCT04447027 1 Suspended National Cancer Institute (NCI)
NCT05020639 1 Recruiting participants Chia Tai Tianqing (CTTQ) Pharmaceutical Group Co, Ltd
NCT04970901 1 Not yet recruiting ADC Therapeutics S.A.
NCT03798314 1 Completed Mayo clinic
NCT04847453 1 Not yet recruiting National Cancer Institute (NCI)
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT04022876 1 Recruiting participants Aileron Therapeutics
NCT02684032 1 Active not recruiting Celcuity
NCT02431208 1 Completed Hoffmann-La Roche
NCT04635683 1 Recruiting participants Ohio State University Comprehensive Cancer Center
NCT03772925 1 Recruiting participants National Cancer Institute (NCI)
NCT04108195 1 Recruiting participants Janssen Research & Development, LLC
NCT04045795 1 Recruiting participants Sanofi
NCT04483505 1 Recruiting participants Fundacion CRIS de Investigación para Vencer el Cáncer
NCT04840888 1 Recruiting participants Eli Lilly and Company
2020-003178-34 1 Unknown Aileron Therapeutics
NCT04172844 1 Active not recruiting Medical College of Wisconsin
NCT03056599 1 Completed Presage Biosciences
NCT01433965 1 Active not recruiting University of California, Davis
NCT01296555 1 Completed Genentech, Inc.
NCT04772885 1 Recruiting participants Kymera Therapeutics
NCT01723020 1 Completed Kartos Therapeutics, Inc
NCT04514159 1 Recruiting participants Zeno Alpha
NCT01749969 1 Active not recruiting Sanofi
NCT03939897 1/2 Suspended National Cancer Institute (NCI)
NCT03643549 1/2 Recruiting participants Haukeland University Hospital
NCT03280563 1/2 Recruiting participants Hoffmann-La Roche
NCT01638936 1/2 Completed Biotest Pharmaceuticals Corporation
NCT03319537 1/2 Recruiting participants Memorial Sloan-Kettering Cancer Center
NCT02119468 1/2 Unknown City of Hope Medical Center
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT04072952 1/2 Recruiting participants Arvinas
NCT03481556 1/2 Active not recruiting Oncopeptides
NCT03560531 1/2 Recruiting participants Zeno Alpha
NCT03363893 1/2 Active not recruiting Carrick Therapeutics Limited
NCT04973605 1/2 Recruiting participants BeiGene
NCT02384083 1/2 Completed PETHEMA Foundation
NCT01946152 1/2 Terminated M.D. Anderson Cancer Center
NCT03393013 1/2 Recruiting participants Kezar Life Sciences
NCT05025800 1/2 Not yet recruiting M.D. Anderson Cancer Center
NCT02004275 1/2 Active not recruiting Alliance for Clinical Trials in Oncology
NCT02773030 1/2 Recruiting participants Celgene
NCT04699188 1/2 Recruiting participants Novartis Pharmaceuticals
NCT04539236 1/2 Not yet recruiting University of Miami
NCT03715478 1/2 Recruiting participants Canadian Myeloma Research Group
NCT03284957 1/2 Recruiting participants Sanofi
NCT04079738 1/2 Active not recruiting Big Ten Cancer Research Consortium
NCT04185883 1/2 Recruiting participants Amgen
NCT04485260 1/2 Recruiting participants Kartos Therapeutics, Inc
NCT02899052 2 Recruiting participants Abbvie
NCT03224507 2 Active not recruiting University of Alabama at Birmingham
NCT04850599 2 Not yet recruiting OHSU Knight Cancer Institute
NCT02654132 2 Active not recruiting Bristol-Myers Squibb
NCT02530424 2 Completed Fondazione Michelangelo
NCT04899349 2 Not yet recruiting Novartis Pharmaceuticals
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT02728102 2 Active not recruiting National Heart, Lung, and Blood Institute (NHLBI)
NCT02874742 2 Active not recruiting Janssen Research & Development, LLC
NCT03314181 2 Recruiting participants Abbvie
NCT02610777 2 Completed Millennium Pharmaceuticals, Inc
NCT04835129 2 Not yet recruiting Medical College of Wisconsin
NCT01415882 2 Recruiting participants Mayo clinic
EUCTR2016-002600-90-BE 2 Active not recruiting HOVON Foundation
NCT03082677 2 Completed Memorial Sloan-Kettering Cancer Center
NCT04024436 2 Recruiting participants Taiho Oncology, Inc.
NCT04033926 2 Active not recruiting Kezar Life Sciences
NCT04436744 2 Active not recruiting Hoffmann-La Roche
NCT02399085 2 Active not recruiting MorphoSys
NCT02217163 2 Completed Singapore General Hospital
NCT03004287 2 Active not recruiting University of Arkansas
NCT02646735 2 Unknown Chinese Academy of Medical Sciences
ACTRN12619001117101 2 Recruiting participants National Health and Medical Research Council, Australia
NCT04876248 2 Not yet recruiting Roswell Park Cancer Institute
NCT04240054 2 Not yet recruiting Medical College of Wisconsin
NCT03763162 2 Recruiting participants M.D. Anderson Cancer Center
NCT02206984 2 Recruiting participants University of Pittsburgh
JPRN-UMIN000029294 2 Enrolling by invitation Japan Breast Cancer Research Group (JBCRG)
NCT05012397 2 Not yet recruiting Rain Therapeutics
NCT03942224 2 Recruiting participants Emory University
ACTRN12616001164482 2 Active not recruiting Celgene
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT02532257 2 Active not recruiting M.D. Anderson Cancer Center
NCT01356290 2 Recruiting participants Medical University of Vienna
NCT04738292 2 Recruiting participants University of Wisconsin, Madison
JPRN-jRCTs031180097 2 Completed Nagoya City University Hospital
NCT02955394 2 Active not recruiting University of Colorado, Denver
NCT03834623 2 Active not recruiting H. Lee Moffitt Cancer Center and Research Institute
NCT01946477 2 Recruiting participants Celgene
NCT01572480 2 Active not recruiting National Cancer Institute (NCI), National Institutes of Health Clinical Center (CC)
NCT03500445 2 Recruiting participants University of Chicago
NCT02572492 2 Unknown Aalborg University Hospital
NCT03691493 2 Recruiting participants Emory University
NCT02538198 2 Active not recruiting Memorial Sloan-Kettering Cancer Center
NCT04191616 2 Recruiting participants Amgen
NCT02315716 2 Active not recruiting University College, London
NCT03314636 2 Recruiting participants Oslo University Hospital
NCT04133636 2 Recruiting participants Janssen Research & Development, LLC
NCT04579380 2 Recruiting participants Seagen (Seattle Genetics) Inc.
NCT02279394 2 Active not recruiting Dana-Farber Cancer Institute
NCT02253316 2 Active not recruiting Washington University School of Medicine
NCT04382300 2 Recruiting participants Shanghai Chest Hospital
NCT03520985 2 Terminated Swiss Group for Clinical Cancer Research
NCT02169791 2 Completed Northside Hospital, Inc.
NCT03069326 2 Active not recruiting Memorial Sloan-Kettering Cancer Center
NCT03188172 2 Active not recruiting University of Leeds
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT02005289 2 Active not recruiting Ohio State University Comprehensive Cancer Center
NCT03161483 2 Completed Celgene
EUCTR2013-005157-75-BE 2 Active not recruiting HOVON Foundation
NCT02951819 2 Completed Janssen Scientific Affairs, LLC
NCT02507336 2 Active not recruiting University of Miami
NCT03386162 2 Active not recruiting UNICANCER
NCT03731832 2 Recruiting participants GWT-TUD GmbH
NCT02195479 3 Active not recruiting Janssen Research & Development, LLC
NCT02516696 3 Active not recruiting Weill Medical College of Cornell University
NCT02545283 3 Terminated Hoffmann-La Roche
NCT03275285 3 Active not recruiting Sanofi
NCT02495922 3 Completed University of Heidelberg Medical Center
NCT04923893 3 Recruiting participants Janssen Research & Development, LLC
NCT04862663 3 Recruiting participants AstraZeneca
NCT04824092 3 Recruiting participants MorphoSys
NCT01734928 3 Active not recruiting Celgene
NCT02422615 3 Active not recruiting Novartis Pharmaceuticals
NCT02990338 3 Active not recruiting Sanofi
NCT03792620 3 Recruiting participants Grupo de Estudos Multicentricos em Onco-Hematologia
NCT01942135 3 Active not recruiting Pfizer
NCT01602380 3 Active not recruiting AstraZeneca
NCT02541383 3 Active not recruiting Intergroupe Francophone du Myelome
NCT03268954 3 Active not recruiting Millennium Pharmaceuticals, Inc
NCT04975308 3 Not yet recruiting Eli Lilly and Company
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phases Trial Status Sponsor
NCT03201965 3 Active not recruiting Janssen Research & Development, LLC
NCT04270409 3 Recruiting participants Sanofi
NCT03539744 3 Recruiting participants Abbvie
NCT03180736 3 Active not recruiting European Myeloma Network
NCT03158688 3 Active not recruiting Amgen
NCT03901963 3 Recruiting participants Janssen Research & Development, LLC
NCT04266795 3 Active not recruiting Takeda
NCT01916252 3 Completed PETHEMA Foundation
NCT04975997 3 Not yet recruiting Celgene
NCT02437318 3 Active not recruiting Novartis Pharmaceuticals
NCT02252172 3 Active not recruiting Janssen Research & Development, LLC
NCT02390869 3 Recruiting participants Fondazione Italiana Linfomi ONLUS
NCT01863550 3 Active not recruiting ECOG-ACRIN Cancer Research Group
NCT03439046 3 Active not recruiting Novartis Pharmaceuticals
NCT04961996 3 Recruiting participants Hoffmann-La Roche
NCT03217812 3 Active not recruiting Janssen Research & Development, LLC
NCT01208766 3 Active not recruiting Stichting Hemato-Oncologie voor Volwassenen Nederland
NCT03234972 3 Active not recruiting Janssen Research & Development, LLC
NCT02107703 3 Active not recruiting Eli Lilly and Company
NCT04680052 3 Recruiting participants Incyte Corporation
NCT03643276 3 Recruiting participants University of Schleswig-Holstein
NCT04305496 3 Recruiting participants AstraZeneca
NCT05020236 3 Not yet recruiting Pfizer
NCT03151811 3 Active not recruiting Oncopeptides
www.beacon-intelligence.com
Table of Trial Updates
Monthly Updates: Trials Updates
Trial ID Phase Trial Status Sponsor
NCT04217967 4 Recruiting participants Peking Union Medical College Hospital
NCT03173092 4 Recruiting participants Millennium Pharmaceuticals, Inc
NCT03401372 U Completed Peking Union Medical College Hospital
www.beacon-intelligence.com
Trial News: Trial Announcements
Trial News: Results Updates
Monthly Updates: News
Trial ID Announcement
NCT03268954 Study did not achieve pre-defined statistical significance for the primary endpoint
of event-free survival
NCT05025800 ALX Oncology announces initiation of trial of evorpacept in combination with
lenalidomide and rituximab
Trial ID Summary
NCT02004275 Shared results in the American Journal of Hematology
NCT04072952 Provided an update in a company presentation
NCT03888612 Provided an update in a company presentation
NCT01602380 Provided an update in a company presentation
NCT02942095 Shared results in Investigational New Drugs
NCT02899052 Shared results in Blood Advances
NCT01433965 Shared results in Bone Marrow Transplantation
www.beacon-intelligence.com
Trial News: Results Updated
Monthly Updates: News
Trial ID Summary
NCT02217163 Shared results in the Blood Cancer Journal
NCT01734928 Shared results in the European Journal of Haematology
NCT03393013 & NCT04033926 Provided an update in a company presentation
NCT03401372 Shared results in Circulation
NCT03560531 Provided an update in a company presentation
NCT04772885 Provided an update in a company presentation
NCT04022876 Provided an update in a company presentation
NCT01877382 Provided an update in a company presentation
NCT01208766 Shared results in the Journal of Clinical Oncology
NCT02541383 Shared results in The Lancet Oncology
NCT01572480 Shared results in JAMA Oncology
NCT04382300 Shared results in BMC Cancer
NCT02572492 Shared results in the European Journal of Haematology
www.beacon-intelligence.com
Drug News: Regulatory Announcements
Monthly Updates: News
Drug Regulatory Announcement
AC0682 Accutar Biotechnology announced FDA clearance of IND
application for phase 1 trial of AC0682 in er-positive breast
cancer
APG-115 Granted fast track designation by the FDA for the treatment
of relapsed/refractory unresectable or metastatic melanoma
www.beacon-intelligence.com
Drug News: New Drugs
Monthly Updates: News
Developer Drug Name Disease Indication Therapeutic Class
University of Michigan ARD-2585 Prostate Cancer PROTAC
Shanghai Meizer
Pharmaceuticals
Shanghai Meizer
Pharmaceuticals PROTACs
B-cell Lymphoma PROTAC
Icahn School of Medicine at
Mount Sinai, University of
North Carolina
MS83 Cancer Indications PROTAC
www.beacon-intelligence.com
Here are this month's highlights from literature exploring early research within the TPD field
• AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss
• Discovery of a Novel BCL-X L PROTAC Degrader with Enhanced BCL-2 Inhibition
Early Papers
www.beacon-intelligence.com
Abstract Analysis
www.beacon-intelligence.com
Drugs for Clinical Abstracts at ESMO 2021
• Fulvestrant had the highest number of abstracts presented at ESMO 2021, due to the large number of trials currently
investigating the drug.
Abstract Analysis –Trials Presented at ESMO 2021
14
2 2 21 1 1
0
2
4
6
8
10
12
14
16
Fulvestrant ALRN-6924 Amcenestrant ZN-c5 Giredestrant BI 907828 Bortezomib
Nu
mb
er
of A
bstr
acts
www.beacon-intelligence.com
Trial Phase Distribution at ESMO 2021
• There is an even distribution of trial phases presented at ESMO 2021, with phase 1 trials being the most common. Half
of the phase 1 trial abstracts were on E3 modulators such as ALRN-6924 and BI 907828.
Abstract Analysis –Trials Presented at ESMO 2021
6
4 4
5
0
1
2
3
4
5
6
7
Phase 1 Phase 1/2 Phase 2 Phase 3
Nu
mb
er
of A
bstr
acts
www.beacon-intelligence.com
Trial Status Distribution at ESMO 2021
• The majority of trials presented at ESMO 2021 are still recruiting participants, 7/9 abstracts from trials recruiting
participants were on SERDs such as fulvestrant and ZN-c5.
Abstract Analysis –Trials Presented at ESMO 2021
9
8
2
1
0
1
2
3
4
5
6
7
8
9
10
Recruiting participants Active not recruiting Unknown Completed
Nu
mb
er
of A
bstr
acts
www.beacon-intelligence.com
Therapeutic Class Distribution at ESMO 2021
• The most common therapeutic class are SERDs due to the high number of abstracts presented for fulvestrant but also
for other SERDs such as amcenestrant, giredestrant and ZN-c5.
0
2
4
6
8
10
12
14
16
18
20
SERDs E3 Modulators Proteasome Inhibitor
Nu
mb
er
of A
bstr
acts
Abstract Analysis –Trials Presented at ESMO 2021
www.beacon-intelligence.com
Abstract Summaries
www.beacon-intelligence.com
ESMO Congress –Trial Data Trial ID Abstract
ID
Drug Title Results Safety
NCT01942135 1103P Fulvestrant 177Lu-DOTATATE efficacy and safety
in functioning neuroendocrine tumors:
A joint analysis of phase II prospective
clinical trials
Sixty-eight patients were enrolled, the majority (88.1%)
with a SR. One (1.5%) patient showed a CR, 21
(32.3%) had a PR and 40 (61.5%) SD. At a median
follow-up of 28.9 months (range 2.2-63.2) median PFS
was 33.0 months (95%CI: 27.1-48.2). Median OS
(mOS) had not been reached at the time of the analysis;
the 2-year OS was 87.8 months
Grade 1-2
hematological toxicity
was the most frequent
NCT02530424 141P Fulvestrant Gene-expression pathways and
dynamics during neoadjuvant chemo-
free therapy predict pathologic
complete response in ER+/HER2+
breast cancer (BC)
In the biomarker population, pCR rate was 28.6% and
16.0% in Fulv and NoFulv cohorts, respectively. At week
2, most of these pathways were also predictive of pCR,
with the addition of trafficking and processing of
endosomal toll-like receptors (TLR, p=4.0E-06, adj
p=0.006), with a similar effect in Fulv and NoFulv
cohorts (p=0.001 and p=0.0006, respectively)
No new safety signals
observed
NCT03449381 1548P BI 907828 A Phase Ia/Ib, dose-escalation/expansion
study of the MDM2–p53 antagonist BI
907828 in patients (pts) with
advanced/metastatic sarcoma
Mean plasma exposures (Cmax and AUC0-inf)
increased with dose. DCR defined as CR + PR + SD)
was 88.9%. 3 of 7 pts with well-differentiated LPS
achieved a PR (all were MDM2-amplified); 1 remained
on treatment >2 years. All 11 pts with DDLPS achieved
SD as best overall response; the median PFS was
approximately 10.8 months (range, 1.3–21 months)
5 patients
experienced DLTs in
arm A and 3 in arm B.
Most common G 3/4
AEs were TCP
(29.6%) and
neutropenia (22.2%)
www.beacon-intelligence.com
Trial ID Abstract
ID
Drug Title Results Safety
2019-001848-21 1654P ALRN-6924 A Phase 1b/2 Study of the Dual
MDMX/MDM2 Inhibitor, ALRN-6924,
for the Prevention of Chemotherapy-
induced Myelosuppression
Results compare favorably to recent
historical results of 63%, 70% and 76%,
respectively. None of the patients treated
at the 0.3 mg/kg ALRN 6924 dose level
had a related SAE; 6% required RBC
and platelet transfusions
No patients reported NCI CTC Grade
≥3 events of nausea, vomiting,
diarrhea; 5% had Grade 3 fatigue.
0.3 mg/kg ALRN 6924 dose level 24
hr prior to topo showed the most
favorable chemoprotection results,
with NCI CTC Grade 3/4 anemia and
thrombocytopenia limited to 19% and
50% of patients, respectively, and a
44% rate of Grade 4 neutropenia
2020-003178-34 1791P ALRN-6924 A Phase 1 Pharmacology Study of the
Dual MDMX/MDM2 Inhibitor, ALRN
6924, in Healthy Volunteers
Robust p21 induction was observed in
bone marrow cells, with peak expression
between 4 hr and 16 hr following ALRN-
6924 administration
Subjects experienced only mild,
transient AEs
NCT02333370 232P Fulvestrant Longitudinal circulating tumor DNA
(ctDNA) analysis in the phase 1b
MONALEESASIA study of ribociclib
(RIB) + endocrine therapy (ET) in
Asian patients (pts) with hormone
receptor–positive (HR+)/human
epidermal growth factor receptor 2–
negative (HER2–) advanced breast
cancer (ABC)
There was a consistent trend of lower BL
ctDNA levels in pts with partial response
(PR) or stable disease (SD) vs pts with
progressive disease; however, there was
no difference in ctDNA levels at on-
treatment time points and EOT by BOR
No new safety signals observed
ESMO Congress –Trial Data
www.beacon-intelligence.com
ESMO Congress –Trial Data
Trial ID Abstract
ID
Drug Title Results Safety
NCT01942135 234P Fulvestrant Effect of palbociclib (PAL) +
endocrine therapy (ET) on time
to chemotherapy (TTC) across
subgroups of patients (pts) with
hormone receptor-
positive/human epidermal
growth factor receptor 2-
negative (HR+/HER2-)
advanced breast cancer (ABC):
Post hoc analyses from
PALOMA-2 (P2) and PALOMA-
3 (P3)
Higher percentage of pts who received vs
who did not receive first subsequent CT
were aged <65 (80% vs 64% in P3, 77%
vs 71% in P3) or had a disease-free
interval (DFI) of ≤12 months
No new safety signals observed
NCT02646735 235P Fulvestrant Efficacy and safety of first-line
therapy with fulvestrant or
exemestane for
postmenopausal ER+/HER2-
advanced breast cancer
patients after adjuvant
nonsteroidal aromatase
inhibitor treatment: A
randomized, open-label,
multicenter study
Median PFS 8.51 months in fulvestrant
group versus 5.55 months in exemestane
group (P = 0.014, HR=0.615, 95%Cl:
0.417∼0.907); ORR of the fulvestrant
group was 19.48% compared to 5.97% of
the exemestane group (P =0.017); TTF
was significantly longer for fulvestrant
versus exemestane (median TTF was
8.38 months in the fulvestrant group and
5.45 months in the exemestane group,
P=0.008)
No significant differences in the
incidence of adverse events and
severe adverse events were observed
between the two groups
www.beacon-intelligence.com
ESMO Congress –Trial Data
Trial ID Abstract
ID
Drug Title Results Safety
NCT02107703 241P Fulvestrant Abemaciclib plus fulvestrant in
participants with HR+/HER2-
advanced breast cancer - a pooled
analysis of the endocrine therapy
naïve (EN) participants in MONARCH
2
Confirmed ORR was 59.1% (95% CI
49.9-68.3). Median follow-up was 9.8
(0.03-73.05) months. PFS and DoR
data are not mature currently
No new safety signals were reported
in the pooled EN cohort, and the
safety profile was consistent with the
previously reported MONARCH 2
population
TBC 253P Fulvestrant Risk factor (RF) identification (ID)
and hyperglycemia (HG) prevention
with alpelisib (ALP) + fulvestrant
(FLV) in PIK3CA-mutated,
hormone-receptor positive (HR+),
human epidermal growth factor-2
negative (HER2-) advanced breast
cancer (ABC)
Median duration of ALP was 86 days
(range 24-442), with 3 pts continuing
to receive ALP at time of analysis
13 pts permanently discontinued ALP
– 9 due to disease progression and 4
due to an adverse event with only 1
due to HG. 9 pts (56%) had G2-4
HG, with only 3 (19%) having G3 HG
and zero having grade 4. Pts with
G2-4 HG had a median of 2 RFs
compared to only 1 RF if no HG
(p=0.03)
NCT03284957 264P Amcenestrant AMEERA-1: Subgroup analyses of
Phase 1/2 study of amcenestrant
(SAR439859), an oral selective
estrogen receptor (ER) degrader
(SERD), with palbociclib in
postmenopausal women with ER+/
human epidermal growth factor
receptor 2-negative (HER2–)
advanced breast cancer (aBC)
In 33 response-evaluable pts with
baseline NGS data: 23 pts had
wtESR1 + other genomic aberrations,
with OR in 6/23 (26.1%) and CB in
16/23 (69.6%); of 11/33 pts with OR,
2/5 had OR and 4/5 had CB; of 9/33
pts with no CB, genomic aberrations
included PIK3CA and TP53
No new safety signals observed
www.beacon-intelligence.com
ESMO Congress –Trial Data
Trial ID Abstract
ID
Drug Title Results Safety
2017-002026-20 265P Fulvestrant Study of samuraciclib (CT7001), a
first-in-class, oral, selective inhibitor
of CDK7, in combination with
fulvestrant in patients with
advanced Hormone Receptor
positive HER2 negative breast
cancer (HR+BC)
Evaluation indicates evidence of
reduction in tumor disease
burden, including a partial
response in one patient who has
been on treatment for ∼ 1 year
Combination treatment was generally well
tolerated, with adverse drug reactions
(AE) of note being G1-2 nausea, vomiting
and diarrhoea
NCT03767335 266P Fulvestrant MEN1611, a PI3K Inhibitor,
combined with trastuzumab (T) ±
fulvestrant (F) for HER2+/PIK3CA
mutant (mut) advanced or
metastatic (a/m) breast cancer
(BC): safety and efficacy results
from the ongoing Phase 1b study
(B-PRECISE-01)
In the evaluable population (n=29)
9 pts showed partial response
(MEN+T 4/11, MEN+T+F 5/18),
and 18 pts had stable disease
(MEN+T 6/11, MEN+T+F 10/18)
as best response. 7 pts were on
treatment > 6 months (MEN+T 3,
MEN+T+F 4), and 1 pt received
MEN+T > 12 months
TEAEs, ≥20% were diarrhoea 64.3%,
nausea 42.8%, asthenia 31%, decreased
appetite 28.6%, anaemia 28.6%, and
hyperglycaemia 23.8%. Most TRAEs
were reversible and manageable by
supportive care. TRAEs caused treatment
interruption in 14 pts (33.3%, 1 pt
definitely) and dose reduction in 6 pts
(16.7%, only allowed in CE) mostly
hyperglycaemia, diarrhoea, nausea,
asthenia and decreased appetite. Serious
TRAEs were experienced by 8 pts;
hyperglycaemia 3 pts, diarrhoea 2 pts,
general physical health deterioration,
generalized oedema, and pneumonitis (1
pt each)
www.beacon-intelligence.com
Trial ID Abstract
ID
Drug Title Results Safety
NCT03280563 267P Fulvestrant Phase Ib/II open-label, randomized
evaluation of second- or third-line
(2L/3L) atezolizumab (atezo) +
entinostat (entino) in MORPHEUS-
HR+ breast cancer (M-HR+BC)
Confirmed ORRs were 6.7% (95% CI: 0.17,
31.95) and 0% (95% CI: 0, 23.16), respectively.
Duration of response was 2.5 months for
atezo+entino (N/A for control). Median PFS was
1.8 months (95% CI: 1.5, 3.6) and 1.8 months
(95% CI: 1.5, 2.7), respectively
40.0% and 21.4% of pts had
Gr 3/4 AEs; no Gr 5 AEs
occurred; serious AEs (SAEs)
occurred in 26.7% and 14.3%
of pts; 6.7% and 0% of pts
had tx-related AEs leading to
tx withdrawal. The most
common tx-related AEs were
nausea (33.3%), vomiting
(26.7%), fatigue (26.7%),
pyrexia (26.7%) and chills
(20.0%) with atezo+entino
NCT03439046 292P Fulvestrant Serum thymidine kinase 1 activity
in patients with hormone receptor
positive (HR+)/HER2 negative
(HER2-) advanced breast cancer
(aBC) treated in first-line with
ribociclib (R) and letrozole (L) in the
BioItaLEE trial
TKa dynamics were strongly predictive of PFS:
P2 indicated a worse outcome vs P1 (HR 2.89;
95% CI 1.57,5.31; p=0.0006), while P3 was
associated with shortest PFS (HR 5.65; CI
2.84,11.2; p<0.0001). For pts in P2, low TKa
No new safety signals
observed
ESMO Congress –Trial Data
www.beacon-intelligence.com
Trial ID Abstract
ID
Drug Title Results Safety
NCT02437318 309P Fulvestrant Antineoplastic (ANP) Therapies (Tx)
After Alpelisib (ALP) or Placebo
(PBO) + Fulvestrant (FUL) in Patients
(Pts) With Hormone Receptor-Positive
(HR+), Human Epidermal Growth
Factor Receptor 2-Negative (HER2–),
PIK3CA-Mutated (Mut) Advanced
Breast Cancer (ABC): An Analysis
From SOLAR-1
In the ALP arm, CT-based 1st subsequent tx was
more frequent in pts with PFS ≤6 mo (56%,
30/54) than pts with PFS >6 mo (40%, 25/63).
FUL and aromatase inhibitors (excluding FUL-
containing regimens) were part of 1st
subsequent tx in 21% (n=24) and 33% (n=39) of
pts in the ALP arm, and 10% (n=14) and 38%
(n=51) of pts in the PBO arm, respectively
No new safety signals
observed
TBC 846P Bortezomib Predictive and prognostic values of
serum VEGF in patients with
multiple myelomas receiving
bortezomib-based therapy
Mean ± SEM of VEGF (pg/ml) was 112.09
±13.25, with range of 4.08-419.50. Seventeen
patients (43.6%) had increased level of serum
VEGF. Patients with increased VEGF level had a
≥ VGPR (very good partial response) lesser than
those patients with normal VEGF level (P= .047)
No new safety signals
observed
NCT04436744 LBA14 Giredestrant Neoadjuvant giredestrant (GDC-
9545) + palbociclib (palbo) vs
anastrozole (A) + palbo in post-
menopausal women with oestrogen
receptor-positive, HER2-negative,
untreated early breast cancer
(ER+/HER2– eBC): Interim analysis
of the randomised, open-label,
phase 2 coopERA BC study
Ki67 suppression was observed in pts with
baseline Ki67 ≥20% (giredestrant: 83%
reduction; A: 71%) or <20% (65% vs 24%). At
week 2, 25% of tumors exhibited CCCA with
giredestrant vs 5% with A (Δ 20%; 95% CI = –
37%, –3%)
Fewer pts had giredestrant-
vs A-related adverse events
(AEs) (28% vs 38%); no
grade ≥3 AEs or serious AEs
were giredestrant-related
ESMO Congress –Trial Data
www.beacon-intelligence.com
ESMO Congress –Trial Outlines
Trial ID Abstract
ID
Drug Title Summary
NCT03284957 333TiP Amcenestrant AMEERA-1: Phase 1/2 study of
amcenestrant (SAR439859), an oral
selective estrogen receptor (ER) degrader
(SERD), with alpelisib in postmenopausal
women with ER+/ human epidermal growth
factor receptor 2-negative (HER2–)
PIK3CA-mutated advanced breast cancer
Primary objective in Part F is to confirm the recommended phase 2 dose
(RP2D) of amcenestrant in combination with alpelisib, based on safety. In
Part G, approximately 34 pts will be treated at the RP2D, the primary
endpoint being safety and tolerability. Secondary endpoints include PK
and antitumor activity. This study is currently recruiting participants
NCT04862663 338TiP Fulvestrant CAPItello-292: a phase 1b/3 study of
capivasertib, palbociclib and fulvestrant
versus placebo, palbociclib and
fulvestrant in HR+/HER2− advanced
breast cancer
CAPItello-292 is a phase 1b/3 study to evaluate the safety and efficacy
of capivasertib, palbociclib and fulvestrant compared with placebo,
palbociclib and fulvestrant in patients with ET-resistant, HR+/HER2– ABC
NCT04579380 557TiP Fulvestrant SGNTUC-019: Phase 2 basket study of
tucatinib and trastuzumab in previously
treated solid tumors with HER2
alterations (Trial in Progress)
SGNTUC-019 is a multi-cohort, open-label, phase 2 study. Cohorts will
enroll pts with HER2+ cervical, uterine, biliary tract, and urothelial
cancers, non-squamous NSCLC, other HER2+ solid tumors (except
GEC, BC, and CRC), HER2-mut non-squamous NSCLC, BC, and other
solid tumors. Primary objective is antitumor activity. Confirmed ORR per
investigator is primary endpoint; secondary endpoints are disease control
rate, DOR, PFS, and OS.
www.beacon-intelligence.com
ESMO Congress –Trial Outlines
Trial ID Abstract
ID
Drug Title Summary
NCT04514159 564TiP ZN-c5 A Phase 1b dose-escalation study of ZN-c5,
an oral selective estrogen receptor degrader
(SERD), in combination with abemaciclib in
patients with advanced estrogen receptor
(ER)+/HER2- breast cancer
This phase 1b, open-label, multicenter study is evaluating the safety,
pharmacokinetics, and preliminary anti-tumor activity of ZN-c5 in combination
with abemaciclib. The primary objective is to determine the maximum tolerated
dose and recommended phase 2 dose
NCT03560531 565TiP ZN-c5 A Phase 1/2 dose-escalation and
expansion study of ZN-c5, an oral
selective estrogen receptor degrader
(SERD), as monotherapy and in
combination with palbociclib in patients
with advanced estrogen receptor
(ER)+/HER2- breast cancer
This phase 1/2, open-label, multicenter study is evaluating the safety,
pharmacokinetics, and anti-tumor activity of ZN-c5 alone and in combination
with palbociclib
www.beacon-intelligence.com
Summary & Coming Up
www.beacon-intelligence.com
Summary
• ESMO 2021 abstracts were mainly centred around SERDs, particularly fulvestrant. This is a reflection of the high clinical
activity in this therapeutic class which does not seem to be slowing down due to the trials still recruiting participants.
• Other therapeutic classes such as E3 modulators and proteasome inhibitors were also present, with assets such as
ALRN-6924 and bortezomib.
• These assets have a large clinical activity so we can expect more data to come in future conferences.
Coming Up
• We hope you found this analysis of ESMO 2021 abstracts useful.
• In the meantime, stay up to date with the latest updates by signing up to our weekly newsletters here
Summary & Coming Up
Thursday, September 30, 2021
THANK YOU
Sofia Rodriguez
TPD Analyst
MAKING DRUG DEVELOPMENT DECISIONS, FASTER.