While ESMO 2023 is just about to begin, Mirati Therapeutics is all geared up to present its discoveries from the KRYSTAL-7 study investigating KRAZATI in first-line setting. There are also other companies including  Jiangsu HengRui Medicine, Revolution Medicines, Jacobio and many more targeting solid tumors harboring KRAS mutation. 

KRAS NSCLC Highlights

• Abstract Number – #LBA65

• Abstract Type – Proffered Paper Session
• Indication – NSCLC
• Target – KRAS-mutated advanced NSCLC
• Title: Could the findings from the KRYSTAL-7 trial be promising enough to drive a major breakthrough?
• Executive Summary –  Mirati Therapeutics is all set to discuss the efficacy and safety of KRAZATI with KEYTRUDA in patients with treatment-naïve, advanced non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation.

Main Content –  Non-Small Cell Lung Cancer (NSCLC) is the predominant form of lung cancer, and it frequently exhibits various genetic mutations. Among these, PD-L1, EGFR, KRAS, ALK, PI3KCA, BRAF, MET, and ROS-1 are the most frequently encountered. KRAS mutations account for a substantial portion and contribute to approximately 15-30% of the mutations or biomarkers in NSCLC.

In 2021 LUMAKRAS (sotorasib) was the only drug that received approval for the adult patients with KRAS G12C mutated locally advanced or metastatic NSCLC in the second line setting. Soon in 2022, Mirati Therapeutics received the accelerated approval for its flagship product KRAZATI in the second-line setting in the United States while the approval decision took a negative turn in Europe. 

Despite such challenges the company is planning to bring this flagship oral targeted treatment  in the first-line setting and is currently investigating its product in Phase II/III trial. The KRYSTAL-7 study evaluates the efficacy and safety of the drug as monotherapy and in combination with KEYTRUDA in Phase II portion and the Phase III portion of the study compares the efficacy of the drug in combination with KEYTRUDA versus KEYTRUDA in patients with locally advanced or metastatic nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50%. 

While the detailed results of KRYSTAL-7 trial is still awaited but as per the data published till now the drug showed better results for liver toxicity which is quite a challenge in LUMAKRAS and the drug along with KEYTRUDA demonstrated promising preliminary clinical activity across all PD-L1 subgroups with an objective response rate (ORR) of 49%. It was also found in a recent finding that the drug and KEYTRUDA showed a confirmed overall response rate of 63% in PD-L1-high patients. 

If approved, the drug is estimated to enter the United States market in 2027 and capture a market of ~USD 4 million in the same year in the first-line setting and target a patient population of ~1300  by 2032 in the United States.

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.