KraS inhibitor Adagrasib compared to Sotorasib's treatment of lung cancer

On October 25, Mirati Therapeutics published two new clinical data on its KRAS G12C selective inhibitor Adagrasib (MRTX849) at the 32nd International Symposium on Molecular Targeting and Cancer Therapy (EORTC-NCI-AACR). It was shown that Adagrasib had an objective remission rate (ORR) of 45% and a disease control rate of 96% for advanced/metastatic non-small cell lung cancer with KRAS G12C mutation, and a 17% orR for colorectal cancer with KRAS G12C mutation and a disease control rate of 94%.
In terms of data alone, Adagrasib is really good, after all, Sotorasib (AMG510) just released the latest data on non-small cell lung and colorectal cancer in September, with ORRs of 32.2% and 7.1%, respectively, and disease control rates of 88.1% and 73.8%, respectively.
if Adgrasib has the potential to win Sotorasib, it's important to analyze the information behind these numbers.
the latter can be found in detail: NEJM: Sotorasib's treatment of KRAS mutated advanced solid tumors has a significant effect.
, however, this comparison is not a head-to-head study, so the direct comparison is still incomplete, after all, there is a difference between the two study groups.
, the following is for informational purposes only.
, the baseline of patients in the group, Adagrasib, was the most white, with a median age of 65, and 89 percent of current or previous smokers and those treated with PD-1/L1.
in Sotorasib's clinical study, 59 NSCLC patients and 42 colorectal cancer patients were included, but the patients were in different dose cohort studies and did not all receive the recommended dose (960 mg). the median age of
is 60, and the proportion of current or previous smokers is comparable to that of Adgrasib, with almost all patients with NSCLC receiving platinum-based chemotherapy and PD-1/L1 treatment, a higher proportion than Adgrasib, with a median line level of 3 for previous systematic anti-cancer treatments.
II, the effectiveness data Adgrasib in the NSCLC queue, assessed 51 patients (14 from I./I.b; 37 from Phase II, although from different studies, but given the same dose), 45% of patients had objective Responses (23/51 patients, 5 of whom had unproven partial reactions and were still receiving treatment), 70% (16/23) of respondents had a optimal response of more than 40% to the tumor, and the patient's disease control rate was 96% (49/51).
65 per cent (33/51) of patients were still receiving treatment within 3.6 months of the median follow-up time, and 83 per cent (19/23) of the respondents had not progressed and were still receiving treatment.
, however, the Adagrasib data were targeted at a clinically active group of patients with ≥1 assessable lesions, not at all cases included in the study.
Adagrasib's ORR in I./I.b should be 33.3% (6/18) and the disease control rate should be 77.8% (14) if calculated on the basis of all patients included in the study /18). In the I./I.b and II. studies, ORR should be 29.1% (23/79) and disease control 62.0% (49/79).
this doesn't seem to show an advantage over Sotorasib data.
the recommended dose (960 mg) queue, 35.3% (12/34) of patients showed PR and the disease control rate was 91.2% (31/34).
, in CRC, Adagrasib single-drug treatment for colorectal cancer with KRAS G12C mutation: ORR 17%, disease control rate of 94%.
, the ORR was 12.5 percent and the disease control rate was 70.8 percent, based on patients included in the study.
3, safety data in 110 patients receiving 600 mg BID, Adagrasib single drug treatment tolerance is good, the incidence of adverse reactions (TRAEs) at any level is 85%, the most common (≥20%) adverse reactions are nausea (54%), diarrhea (51%), vomiting (3) 5%), fatigue (32%) and elevated ALT (20%), the proportion of adverse reactions of level 3 and above was 32%, 1 case of relapsed pneumonia and heart failure of 5 adverse reactions, 4.5% of patients due to treatment-related adverse events led to suspension of drugs, adverse reactions led to drug suspension rate of 7.5%.
, sotorasib has a higher rate of adverse reactions than other events.
125 patients reported adverse events (96.9%) during treatment, the most common being diarrhoea (38 cases (29.5%)), fatigue (30 cases (23.3%)) and nausea (27 cases (20.9%).
level 3 or higher adverse events (52.7%) were reported in 68 patients.
a total of 73 patients (56.6%) experienced treatment-related adverse events, 2 patients (1.6%) had serious adverse events, and 15 patients (11.6%) reported adverse events related to level 3 or 4 treatment.
treatment-related levels of adverse events include elevated levels of alanine transaminase (4.7%), diarrhea (3.9%), anemia (3.1%), elevation of acetone transaminase (AST) (2.3%), and blood Increased levels of alkaline phosphatase (1.6%), hepatitis (0.8%), lymphocyte count decreased (0.8%), γ-glutamine transirase levels increased (0.8%) and hyponatrexemia (0.8%).
one patient (0.8%) reported an increase in treatment-related level 4 ALT, and one patient (0.8%) was interrupted by an increase in treatment-related levels of level 3 ALT and AST.
Adagrasib and Sotorasib both had level 5 adverse events, but there was little difference in the probability of suspension due to adverse reactions (7.5% vs 7.0%).
, in terms of effectiveness, Adagrasib had a total ORR of 29.1% (23/79 for all patients in the study, the same dose of the drug), and Sotorasib was in the recommended dose (960 mg) queue, 35.3% (12/34) of patients showed PR, and Sotorasib had a higher disease control rate than Adagrasib;
Of course, the above data are not the final clinical data of the two drugs, the clinical sample size is small, not to be a head-to-head clinical comparison, only in the current data to spy on the potential clinical effectiveness of the two KRAS G12C inhibitors differences.
summary, it is concluded from the data that the results of phase I and Phase II clinical trials show that there is no significant difference between the two in the therapeutic effect, but in adverse reactions, the adverse reactions of the inhibitor Adagrasib (MRTX849) were better than those of Sotorasib (AMG510).
from the results of Phase III, it can be seen that the inhibitor Adagrasib (MRTX849) treatment effect is higher than soorasib (AMG510), MRTX849 objective mitigation rate is higher than AMG510, disease control rate is also much higher.
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