Abstract 1121P
Background
KRASG12C mutation is an oncogenic driver identified in ∼13% of NSCLC. Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRAS G12C activation. Pooled Phase 1,2 data from CodeBreaK 100 reported an objective response rate of 40.7%, a 2-year overall survival rate of 32.5% and a well-tolerated safety profile with sotorasib.
Methods
Prior to the EMA approval in 01/2022, French Health Authorities considered sotorasib an innovative drug and allowed a nominative Temporary Authorization of Use (nATU) in 12/2020 and then approved a cohort ATU (cATU) in 06/2021. Eligible pts were adults with KRASG12C driven mNSCLC who progressed after at least one prior line of systemic therapy.
Results
From 08/2021 to 01/2022, data from 679 pts were collected in 197 centers including 549 pts via cATU and 130 pts previously treated via nATU. 651 were exposed to sotorasib. Pts’ main characteristics are presented in the table. Table: 1121P
| Variable | Results |
| Age years median | 65.6 [35.9-87.7] |
| n=679 | |
| Sex % Male / female | 58.6 / 41.4 |
| n=679 | |
| Smoking status % Never / former / current | 3.5 / 81.1 / 15.3 |
| n=678 | |
| Histology % | |
| n=676 | |
| Adenocarcinoma | 95.1 |
| Other | 4.9 |
| ECOG performance status % | |
| n=679 | |
| 0 | 20.2 |
| 1 | 61 |
| 2 | 16.9 |
| 3 | 1.9 |
| PDL-1 status % | |
| n=679 | |
| <1 | 38.9 |
| [1-49] | 31.1 |
| ≥ 50 | 21.6 |
| Undetermined | 8.4 |
| KRAS testing % | |
| n=679 | |
| Sample: | |
| Tissue | 97 |
| DNA circulating tumor | 2 |
| Both | 1 |
| Modalities: | |
| Next Generation Sequencing | 83.1 |
| Single Gene | 16.2 |
| Both | 0.7 |
| Main metastasis location % | |
| n=679 | |
| Lung | 51.4 |
| Bones | 39.2 |
| CNS total (active) | 31.8 (10.9) |
| Extra-thoracic lymph nodes | 20.6 |
| Pleural | 19 |
| Adrenal | 15.9 |
| Liver | 11.6 |
| Sotorasib therapy line % 2 / 3 / ≥4 | 49.1 / 29.8 / 21 |
| N=651 | |
| Median of prior lines nATU / cATU pts | 2 /1 |
| N=677 |
Across prior lines and before exposure to sotorasib, pts received Chemotherapy (CT) alone, CT and Immunotherapy (IO), IO alone in 14.6%, 80.8%, 4.6% of cases respectively. In 1st line, 45.4% of pts received CT-IO (among them, 71.4% had sotorasib in 2nd line), 35.2% CT, 13.7% IO and 5.4% CT-bevacizumab. In 51% of pts, the immediate prior line before sotorasib contained IO. The median duration of sotorasib treatment was 7.5 [1.5-11.3] months for pts from nATU (n = 121/130) and 3.5 [0.2-5.7] months for new pts in cATU (n = 152/549) for a median follow up of 7.7 [1.9-11.3] and 4.0 [0.2-5.7] months respectively.
Conclusions
Broad KRAS G12C testing allowed 651 pts with KRASG12C driven mNSCLC ineligible to sotorasib clinical trials to be treated. Prior lines treatments received by cATU pts are in accordance with CodeBreaK trial pts. Further RW data on efficacy and safety are the subject of an ongoing French study NCT05273047.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Amgen.
Funding
Amgen.
Disclosure
J. Cadranel: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Sanofi, Takeda, Pfizer, Amgen; Financial Interests, Institutional, Other, Grant: AbbVie, Pfizer; Financial Interests, Personal, Advisory Board, Amgen: Lilly. X. Quantin: Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Other, Educational support: AstraZeneca. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Family member is an employee: AstraZeneca. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Seattle Genetics, Takeda; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. J.B. Auliac: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, BMS, Roche; Non-Financial Interests, Personal, Invited Speaker: Sanofi, Takeda. S. Couraud: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, MSD, Roche, Takeda, Sanofi, Fabentech; Financial Interests, Institutional, Funding: Amgen, AstraZeneca, BMS, Chugai, MSD, Novartis, Roche, Takeda, Bayer, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai, Takeda; Financial Interests, Personal, Other: Laidet. A. Madroszyk Flandin: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Roche. H. Curcio: Financial Interests, Personal, Invited Speaker: Viatris. A. Métivier: Financial Interests, Personal, Training: Takeda, MSD, BMS; Financial Interests, Personal, Sponsor/Funding: Novartis, Pfizer. O. Bylicki: Financial Interests, Personal, Expert Testimony: BMS, AstraZeneca, MSD, Roche; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, MSD, Roche. P. Tomasini: Financial Interests, Personal, Advisory Role: BMS, AstraZeneca, Roche, Amgen, Johnson & Johnson, AbbVie, Takeda. R. Veillon: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Roche; Financial Interests, Personal, Advisory Board: Janssen, Takeda; Financial Interests, Personal, Expert Testimony: AstraZeneca; Non-Financial Interests, Personal, Other, congress registration: Pfizer, Roche; Financial Interests, Institutional, Research Grant: Merck, Takeda, Novartis, GSK, AstraZeneca. C. Damade, C. Mourad, C. Veillard: Financial Interests, Personal, Full or part-time Employment: Amgen. H. Lena: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Roche, MSD, Pfizer, AstraZeneca, Lilly, Takeda, Amgen. All other authors have declared no conflicts of interest.