KRAS, TIGIT, CD47... Do you know the latest developments in these popular targets?

Recently, the American Society of Clinical Oncology (ASCO) annual meeting opened onlineAs one of the world's largest clinical oncology conferences, ASCO's annual conference is where pharmaceutical and biotechnology companies announce the latest advances in innovative therapiesThe latest clinical results for innovative therapies targeted at a number of popular targets were presented at the ASCO conferenceThese targets include the innovative immunocheckpoint inhibitor TIGIT, the "Don't Eat Me" signal CD47, the former "non-drug- target KRAS" kraS, and the emerging target B cell maturity antigen (BCMA) in the field of blood cancerIn today's article, the Pharmaceutical Mingcon content team will take stock of ASCO's latest developmentsFollowing the success of the first generation of immunocheckpoint inhibitors, represented by PD-1/PD-L1, CTLA-4, an important direction in the development of cancer immunotherapy is the search for a new generation of immunocheckpoint inhibitors that can be used in conjunction with existing checkpoint inhibitors to further improve the effectiveness of cancer treatmentIN RECENT YEARS, TIGIT HAS BECOME AN INNOVATIVE IMMUNE CHECKPOINT TARGET THAT HAS ATTRACTED THE ATTENTION OF THE INDUSTRYAccording to BioCentury, at least 12 TIGIT targeted therapy research and development projects are now in the clinical development phaseAmong them, Roche's anti-TIGIT antibody tiragolumab is undoubtedly the focus of attentionEarlier this year, Roche announced that it was pushing the candidate therapy into Phase 3 clinical development, demonstrating confidence in itAt ASCO's annual meeting, Roche announced the results of tiragolumab's Phase 2 clinical trial CITYSCAPEIn the treatment of PD-L1 high expression (TPS -50%) patients with metastatic non-small cell lung cancer as a first-line therapy, tiragolumab and Tecentriq combined with an objective remission rate of 66%, higher than Tecentriq single drug therapy (24%)This combination reduces the patient's risk of disease progression or death by 70% (HR-0.30, 95% CI, 0.15-0.61)The level OF PFS in the treatment group was not yet reached, while the Tecentriq single drug group PFS was 4.1 monthsGilead Sciences has acquired Forty Seven, a biotech company that develops CD47 antigensAt ASCO's annual meeting, Gilead Sciences announced the results of phase 1b clinical trials for the first-line treatment of patients with high-risk myelogenic hyperplasia syndrome (MDS) and acute myeloid leukemia (AML) in combination with aphasiaThe results showed that magrolimab combination therapy achieved an objective remission rate (ORR) of 91% and a full remission rate (CR) of 42% when treating patients with high risk of MDS (n-33) In AML patients who were unable to receive strong chemotherapy (n-25), this combination of therapies reached 64% ORR and 56% CR or complete remission accompanied by incomplete hematologic remission The median mitigation duration and the median total lifetime were not yet reached at the time of the results report KRAS is one of the most common mutations in human tumors, but it has long been considered an "non-drug" target Last year, a breakthrough was made in the development of drugs directly targeting KRAS, and the KRAS G12C inhibitors developed by several companies entered the clinical development phase Amgen's AMG 510 is the first KRAS G12C inhibitor to publish clinical results, which has shown positive results in the treatment of non-small cell lung cancer patients with KRAS G12C mutations At this year's ASCO annual meeting, Amkin announced the effects of AMG 510 in the treatment of patients with colorectal cancer and other non-NSCLC solid tumors with KRAS G12C mutations The results showed that patients receiving a dose of AMG 510 had an ORR of 12% and an 80% disease control rate (DCR) in the treatment of patients with advanced colorectal cancer (CRC) The median progression-free survival (PFS) was 4.2 months, and when the median follow-up time was nearly 8 months, the median total survival period had not yet been reached These patients are of a very difficult type, with 69% of them having received more than three pre-treatments In the treatment of non-NSCLC or CRC solid tumor patients, 3 patients with appendicone, melanoma, and endometrial cancer were partially alleviated, and 6 of the 8 pancreatic cancer patients who received assessment were stable, with 3 having a 30% reduction in tumor load compared to the baseline Of a total of 19 patients who received an acceptable assessment, 13 had reduced tumors These patients have also been treated with a variety of pre-treatments Currently, Phase 2 clinical trials for AMG 510 treatment of NSCLC and CRC patients have been registered, and Phase 2 clinical trials for patients with NSCLC are expected to be available this year Amjin has also launched six Phase 1b clinical trials to test the efficacy and safety of different combination therapies based on AMG 510, and the company has initiated phase 3 validation clinical trials to further test the effectiveness of AMG 510 in the treatment of Patients with NSCLC The strategy of targeting KRAS is not limited to direct targeting of KRAS mutants The onvansertib, developed by Cardiff Oncology (formerly Trovagene), is a third-generation oral PLK1-specific inhibitor PLK1 is overexpressed in many types of cancer, and studies have shown a "synthetic lethal" relationship between PLK1 and KRAS This means that tumors carrying the KRAS gene mutation are particularly sensitive to PLK1 inhibitors By targeting PLK1, onvansertib can target all common KRAS gene mutations In Phase 1b/2 clinical trials, onvansertib was used in conjunction with FOLFIRI and Avastin as a 2-line therapy for patients with metastatic colorectal cancer with KRAS mutations These patients have been treated with the standard therapy of FOLFIRI and Avastin The results showed that onvansertib combination therapy achieved an 89% disease control rate in 9 assessable patients, of which 4 patients received objective remission and 4 patients were stable Median PFS was over 6 months old and six patients are still being treated BMCA is one of the hottest targets in the field of blood cancer, with the number of cell therapies targeting this target nearly doubling in the past year alone Car-T therapy JNJ-4528, developed jointly by Nanjing Legends and Janssen, is a superior cell therapy in a number of research therapies aimed at BCMA Preliminary clinical results presented at the ASH annual meeting last year showed that the treatment achieved a 100% objective remission rate in the CARTITUDE-1 clinical trial for patients with recurrent/refractive multiple myeloma The latest clinical data for CARTITUDE-1, released today, were even better, with 25 of the 29 patients treated achieving complete remission while maintaining an objective remission rate of 100% At the ASH annual meeting, only 20 patients achieved complete remission This means that over time, patients treated with JNJ-4528 have a greater degree of remission This offers hope for long-term deep remission for patients Currently, the therapy is being tested in a Phase 3 clinical trial called CARTITUDE-2 The