Rasagiline

Immunotherapies are crucial for multiple myeloma (MM) but face resistance and relapse. Proteasome inhibitors (PIs) and targeted therapies like BCL2 and BRAF/MEK inhibitors offer alternatives. Clonal evolution and subclonal mutations drive disease progression. Combination therapies, including melphalan, increase mutational load. Resistance to lenalidomide and anti-CD38 antibodies is common, but combinations like carfilzomib, daratumumab, and dexamethasone improve progression-free survival (PFS). BCMA-targeted antibody-drug conjugates (ADCs) show promise. Targeted inhibitors for BCL2, BRAF/MEK, and NSD2 benefit refractory patients. Despite clinical promise, access to these therapies is limited, highlighting the need for cost-effective treatments and innovative approaches.

Dr Victoria Kunene, a consultant medical oncologist at Queen Elizabeth Hospital Birmingham, is spearheading personalized mRNA vaccines for colorectal cancer as part of the NHS Cancer Vaccine Launch Pad initiative. These vaccines aim to prevent and treat cancer by re-educating the immune system to recognize and eliminate cancer cells. The trial focuses on high-risk stage two and three colon cancer patients with detectable circulating tumour DNA, offering them a bespoke vaccine after standard chemotherapy. The initiative seeks to improve patient outcomes and survival rates by integrating advanced genomic sequencing and immunotherapy.

PAS-004, a next-gen MEK inhibitor, showed favorable safety and tolerability in a phase 1 trial for MAPK pathway–driven advanced cancers, with no drug-related serious AEs. The trial's third cohort will test 8 mg doses, and pharmacokinetic data revealed a long half-life of 67.9 hours, suggesting potential for less frequent dosing. Early efficacy signals, including prolonged stable disease in a CRC patient, indicate PAS-004's potential to outperform current MEK inhibitors.

The phase 3 IKF-AIO-RAMTAS trial found no significant OS improvement with ramucirumab + TAS-102 vs TAS-102 alone in heavily pretreated mCRC patients, though benefits were seen in female patients and those with left-sided tumors. The combination showed improved PFS and DCR but increased hematotoxicity and dose reductions.

J&J's Rybrevant shows promise in colorectal cancer, with Phase II data suggesting it makes metastatic patients eligible for curative surgery, leading to a 49% ORR in the OrigAMI-1 study.

Amgen presents new oncology data at ESMO Congress 2024, highlighting targeted therapies for colorectal, lung, prostate, and gastric cancers, reflecting their strategy to advance diverse modalities for difficult-to-treat cancers.

RMC-6236, a non-covalent pan-RAS(ON) inhibitor by Revolution Medicines, shows efficacy in 'undruggable' RAS mutant tumors via a 'tri-complex' mechanism involving cyclophilin A. AACR 2024 meeting presentation covers its discovery, preclinical profile, and clinical updates.

Tempus AI announced four abstracts accepted for ESMO Congress 2024, focusing on AI's impact on clinical trials, ctDNA monitoring, genomic profiling in lung cancer, and RAS/BRAF mutations in MSI/dMMR colorectal cancers.

New therapies like trifluridine/tipiracil plus bevacizumab and fruquintinib expand options for refractory metastatic colorectal cancer (mCRC). Efforts focus on moving targeted therapies to earlier lines and developing novel therapies for previously undruggable mutations. Immunotherapy lags in mCRC, but combinations and new approaches show promise. Enrolling in clinical trials is crucial for further progress.

Novartis' HRO761, an oral allosteric WRN helicase inhibitor for MSI-high and dMMR tumors, emphasizes early HTS assay selection and medicinal chemistry strategies for optimizing LipE, TPSA, chameleonicity, and non-classical zwitterions. Discusses X-ray structure binding, differentiation from VVD-214, preclinical activity, clinical status, and chemical synthesis.