Phesgo and Tecentriq Performance and Approvals
Divarasib in CRC: Positive early combination data at AACR
Potential for best-in-class profile
Divarasib (KRAS G12Ci)
in vitro proliferation assay
Roche
AACR
American Association
for Cancer Research
FDA BTD
Ph lb results for divarasib + cetuximab in advanced or metastatic CRC
ORR results
20
Viability IC50 UM
(free drug)
0.1
0.01
0.001
0.0001
0.00001-
Divarasib
G12C
non-G12C
Viability IC50 UM
(free drug)
0.1
0.01
0.001
0.0001
0.00001
a
Sotorasib
G12C
non-G12C
++H+
Viability IC 50 UM
(free drug)
10
0.1
0.01
0.0011
0.0001
0.00001-
Adagrasib
G12C
non-G12C
**
Best SLD Change from Baseline (%)
0
-20-
-40
-60-
-80-
Best Response
SD PR * Confirmed
GDC-6036 Dose Level (mg) 400 400 400 400 200 400 400 400 400 200 200 400 400 400 400 400 400 400 400 400 400 400 400 400 400 400 400 400 400
Baseline SLD (mm) 15 74 87 144 90 121 84 84 109 38 43 65 59 59 87 86 33 43 35 189 90 24 83 59 57 83 35 62 53
Days on Treatment 181 167 181 49 84 80 169 210 167 232 138 140 197 173 167 92 168 138. 183 124
174 294
Active on Treatment
Prior KRAS G12Ci
Y
Y N Y
N N N N
N N Y
N N N N Y N N N Y N Y N
Y
Y Y N Y N Y
Y
Y
Y
N
Y
Y
N N N N N N N N
N
N
161 213 342 160 188 71 265
N Y Y Y Y Y
N N Y N N N
Indicates 24 months on treatment
•
•
Irreversible covalent inhibitor of KRAS G12C
More potent and selective in vitro than
sotorasib and adagrasib
•
Promising Ph lb results in CRC with unconfirmed / confirmed ORR = 66% / 62% and
manageable safety profile
Strong responses in several other indications, including 2L+ NSCLC
•
Granted FDA BTD for 2L NSCLC
•
Confirmatory pivotal Ph III trial in 2L+ NSCLC initiated in Q4 2022
•
KRAS is the most frequently mutated oncogene,
•
Ph II/III (BFAST) with divarasib cohort in NSCLC ongoing
occurring in more than 25% of all cancers
Source: Purkey et al. AACR 2022; Phase lb study of GDC-6036 in combination with cetuximab in patients with colorectal cancer (CRC) with KRAS G12C mutation, Desai et al., AACR annual meeting 2023; KRAS-kirsten rat sarcoma;
G12C-glycine-to-cysteine substitution at codon 12; IC 50-inhibitory concentration; BTD=breaktrough therapy designation; CRC=colorectal cancer; NSCLC=non-small cell lung cancer; ORR=overall response rate; SLD-sum of lesion
diameter; SD-stable disease; PR=partial response; Lumakras (sotorasib) is a registered trademark/product of Amgen; Krazati (adagrasib) is a registered trademark/product of Mirati Therapeutics
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