German drugmaker Boehringer Ingelheim has entered clinical studies with its pan-KRAS inhibitor BI 1701963, going after one of the most commonly mutated oncogenes—until recently considered undruggable. Previously, in September, the Ingelheim, Germany-based pharma entered a $720 million deal with Mumbai-based drugmaker Lupin to test its KRAS inhibitors with Lupin’s MEK inhibitor in gastrointestinal and lung cancers. KRAS and its role as a proto-oncogene in driving tumors was identified 30 years ago, but most attempts to tackle KRAS failed because the molecule lacks distinct drug-binding pockets. Amgen was the first to develop an inhibitor of the KRAS G12C-mutated form, the most frequent KRAS mutation in non-small-cell lung cancer (NSCLC). The company’s AMG 510 is the most clinically advanced KRAS inhibitor and in phase 1 testing in patients with KRAS G12C-mutant cancer. At the September European Society for Medical Oncology (ESMO) meeting in Barcelona, Spain, AMG 510 led to 7 partial responses and 6 cases of stable disease in 13 evaluable patients with NSCLC. At ESMO, Amgen also reported data from 12 evaluable patients with colorectal cancer: AMG 510 led to 1 partial response and 10 cases of stable disease. Other KRAS inhibitors are not far behind. Mirati Therapeutics expects data this quarter from a phase 1/2 trial testing MRTX849, and Johnson & Johnson is evaluating JNJ-74699157 (ARS-3248) in a phase 1 study. Like Amgen, both companies are enrolling patients with KRAS G12C-mutant cancer, as their small-molecule drugs are KRAS G12C inhibitors. As for Boehringer, its phase 1 trial will evaluate BI 1701963 as monotherapy and in combination with Mekinist (trametinib) in 140 patients. Boehringer’s drug is distinct from its competitors in that it is a pan-KRAS inhibitor that targets both KRAS G12C and SOS1, a protein responsible for RAS activation. The study is recruiting patients with any KRAS mutation.