Pharma Update
Divarasib in KRAS G12C-mutant tumors
Potential best-in-class molecule; Ph II/III in 2L NSCLC ongoing
KRAS G12C inhibitor
Best-in-class potential supported by early clinical data
Proliferation potency/selectivity
GDC-6036
10
101
0.11
Sotorasib
0.11
0.01
Adagrasib
NONENE
0.1
0.01
0.0011
0.00011
0.00001-
G12C
non-G12C
0.011
0.001
0.0001
0.00001-
G12C
ztg-use
0.001
0.00011
0.00001
G12C
non-G12C
Overall response rates
Roche
FDA BTD
The NEW ENGLAND
JOURNAL of MEDICINE
PFS (all doses) in 2L+ NSCLC monotherapy
Indication
Regimen
2L+ NSCLC
Monotherapy
2L+ CRC
Monotherapy
2L+ CRC
Confirmed ORR
53% (all doses)
56% (400mg dose)
29% (all doses)
36% (400mg dose)
62%
Divarasib + cetuximab
Percentage of Patients
100
75-
50-
25-
mPFS=13.1 months
HHH
0-
0
3
6
9
12
15
18
21
24
Months
No. at Risk 60
48
37
23
14
17
4
1
0
•
•
Divarasib is an irreversible covalent
inhibitor of mutant KRAS G12C
protein resulting in a locked inactive
conformation
Best-in-class potential being more
potent and selective in vitro than
sotorasib and adagrasib
•
Robust clinical benefit in patients with KRAS G12Cm NSCLC and CRC as monotherapy and in combination
Manageable safety with reversible adverse events across tumor types
Pivotal Ph II/III trial in 2L NSCLC (BFAST) with divarasib cohort ongoing
Ph lb trials in 1L NSCLC (KRASCENDO) in combination with pembrolizumab and in 1L, 2L CRC (INSTRINSIC) in
combination with cetuximab +/- FOLFOX/FOLFIRI) initiated
Purkey H. et al., AACR 2022; Sacher A. et al., NEJM Aug 2023; Desai J, et al., AACR 2023; NSCLC= non-small cell lung cancer; CRC=colorectal cancer; PFS=progression free survival; mPFS=median progression free survival;
FOLFOX=folinic acid, fluorouracil and oxaliplatin; FOLFIRI=folinic acid, fluorouracil and irinotecan; ORR-Overall Response Rate
78View entire presentation