KRAS-Mutated CancersClinical Trials Landscape Therapies under investigation for KRAS-Mutated Cancers
June 2020
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Executive Summary
• As per clinical phase of development, there are currently ~64 assets in Phase I, ~41 assets in Phase I/II, ~86 assets in Phase II, ~17 assets in Phase III clinical development for KRAS-mutated cancer
• As per indication, colorectal cancer has the highest number of clinical trial trials among KRAS-mutated cancer which are ~93 trials in number, followed by NSCLC (~53 trials), Solid tumors (~32 trials), Pancreatic cancer (~13 trials), Breast cancer (~13 trials), Multiple Myeloma (~8 trials) and others
• As per MoAs, EGFR inhibitors are seeing maximum activity in clinical trials (~95 trials) for KRAS mutated cancer, followed by MAP inhibitors (~45 trials), PD-1 inhibitors (~15 trials), Pi3k inhibitors (~9 trials), KRAS Inhibitors (~ 7 trials)
• As per company/sponsors, the highest number of clinical trials in KRAS mutated cancer are being carried out by Amgen (~32 trials), Novartis (~18 trials), Merck (~17 trials), Roche/Genentech (~16), Pfizer (~16 trials), AstraZeneca (~11 trials), Eli Lilly (~11 trials), BMS (~11 trials), Array Biopharma (~11 trials), GSK (~8 trials), Boehringer Ingelheim (~5 trials), Takeda (~5 trials)
Phase I assets under investigation in KRAS mutated cancers (1/3)
BKM120
NCT01513356/
Novartis
Mesenchymal-marker
based ferrofluid
NCT02080650/Jansse
n Diagnostics
KRAS peptide
vaccine|Nivolumab|Ipi
limumab
NCT04117087/Bristol
-Myers Squibb
JNJ-74699157
NCT04006301/Jansse
n Research &
Development
BI 1701963|
Trametinib
NCT04111458/Boehri
nger Ingelheim
Sotorasib + Other
Anti-cancer
Therapies*
NCT04185883/Amge
n
MEK162 and
mFOLFIRI
NCT02613650/Array
BioPharma
Decitabine +
panitumumab
NCT00879385/Amge
n Inc.
Pembrolizumab +
Trametinib
NCT03299088
Novartis
REOLYSINÂ
+FOLFIRI &
bevacizumab
NCT01274624/
Oncolytics Biotech
AMG 510
NCT04380753/Amge
n
HL-085| Docetaxel
NCT03990077/Shang
hai Kechow Pharma.
AZD4785
NCT03101839/Astra
Zeneca
Panitumumab|
Cabozantinib
NCT02008383
Exelixis
AUY922|Cetuximab
NCT01294826/Novar
tis
Cobimetinib|
MEHD7945A
NCT01986166/Genen
tech.
GSK2110183+
Bortezomib+Dexamet
hasone
NCT01428492/
Novartis
PF-00299804
NCT00728390/Pfizer
HLX55
NCT04169178/
Henlix
BYL719|MEK162
NCT01449058/Array
BioPharma
GSK1120212+
Gemcitabine
NCT01324258/
GlaxoSmithKline
SCB-313
NCT03869697/Clover
Bio AUS
MM-121+Irinotecan+
Cetuximab
NCT01451632/Merri
mack
gedatolisib+Docetaxel
+ Cisplatin
NCT01920061/Pfizer
Erlotinib+PF-
02341066
NCT00965731/Pfizer
TNO155+ EGF816
(nazartinib)
NCT03114319/Novart
is
LXH254+LTT462+Tr
ametinib+ Ribociclib
NCT02974725
Novartis
Trametinib+fluoroura
cil+ radiation therapy
NCT01740648/Terenc
e Williams
Binimetinib+Pemetre
xed+Carboplatin
NCT02185690/Novart
is
RO5126766+VS-6063
NCT03875820/Chuga
i
Pancreatic CancerColorectal/Rectal cancerNon-Small Cell Lung CancerBreast CancerMultiple MyelomaSolid Tumours
Phase I assets
Active, Not recruiting
Not yet recruiting
Recruiting
*Other Cancer Therapies: Drug: PD1 inhibitorDrug: MEK inhibitorDrug: SHP2 allosteric inhibitorDrug: Pan-ErbB tyrosine kinase inhibitorDrug: PD-L1 inhibitorDrug: EGFR inhibitorDrug: Chemotherapeutic regimen
ASCO 2020 Readouts
Not shown…Phase I/II, Phase II, Phase III
ASCO Results 2020KRAS Mutated Cancers
ASCO20 Alert: AMG 510 monotherapy was well tolerated in KRASG12C mutated CRC
Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is associated with poor prognosis in colorectal cancer (CRC). AMG 510 is a first-in-class small molecule that specifically and irreversibly inhibits KRASG12C by locking it in the inactive guanosine diphosphate-bound state. In a previous interim analysis of the phase 1, first-in-human trial of AMG 510, we observed a favorable safety profile and preliminary antitumor activity in patients (pts) with advanced solid tumors harboring KRAS p.G12C. Here, we present updated data in pts with CRC.
Methods:Key inclusion criteria were KRAS p.G12C mutation identified through molecular testing, measurable disease, and progression on standard therapy. Primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), as assessed per RECIST 1.1, and overall survival (OS). Oral daily doses of 180, 360, 720, and 960mg were tested in the dose escalation phase, and 960mg dose was selected for the expansion phase.
Results:As of Jan 8, 2020, 42 pts with CRC (21 female [50%], median age: 57.5 years [range: 33–82]) were enrolled and dosed (25 on 960mg). All pts received prior systemic therapies; 19 pts (45.2%) received > 3 prior lines. Median follow-up was 7.9 months (mos) (range: 4.2–15.9). 13 pts (31.0%) died, and 8 pts (19.0%) remained on treatment (tx). 22 (52.4%) and 8 (19.0%) pts had remained on tx for more than 3 and 6 months, respectively. Progressive disease was the most common reason for tx discontinuation. 20 pts (47.6%) had tx-related adverse events (TRAEs): 18 (42.9%) had grade 2 or lower TRAEs; 2 (4.8%) had grade 3 TRAEs, which were diarrhea (2.4%) and anemia (2.4%). There were no dose-limiting toxicities, fatal TRAEs, or TRAEs leading to tx discontinuation. Overall, ORR and DCR were 7.1% (3/42) and 76.2% (32/42), respectively. At 960mg, ORR and DCR were 12.0% (3/25) and 80.0% (20/25). 3 pts with PR had duration of response of 1.5, 4.2, and 4.3 months, respectively, and their responses were still ongoing at data cutoff. In all pts treated with all doses, median duration of stable disease was 4.2 mos(range: 2.5[+]–11.0). PFS/OS will be reported.
Abstract Number: 4018 Indication: Colorectal cancer Source Reliability: High
Background
Methods & Results
Drug Name(s): AMG-510 Dev. Stage: Phase 1/2 (NCT03600883) MOA: K-Ras inhibitor (Small Molecule)
In pts with heavily pretreated KRAS p.G12C mutant CRC, AMG 510 monotherapy was well tolerated, with the majority of pts achieving disease control. Study is ongoing
1. https://meetinglibrary.asco.org/record/185490/abstract
Conclusion Sources: Secondary
CodeBreak 100: Activity of AMG 510, a novel small molecule inhibitor of KRASG12C, in patients with advanced colorectal cancer.
Abstract Title
Not shown…ASCO results for other Trials
Methodology & Disclaimer• All the trials captured are either industry
sponsored/associated or run in collaboration with other hospitals or academic groups or institutes
• The trials/assets captured are global in nature with no filters applied on trial location or company headquarters
• All the trials with status other than withdrawn/ terminated/ suspended have been included
• There are no filters applied on study start date or primary completion date, giving the exercise a wider scope
• The trials/assets with direct/undirect action on KRAS-mutated cancer have been captured
• Information covered in each cell are as follows: Asset in monotherapy/combination; NCTId, sponsor company, Trial status and the indication the trial is active in
• Source: Trial Trove, a paid subscription database, Clinical Trials.gov, company press release, ASCO posts, Pubmed/research articles and general secondary
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