Dostarlimab

The FDA granted Jemperli (dostarlimab-gxly) a breakthrough therapy designation for locally advanced dMMR/MSI-H rectal cancer, marking its second designation for this population. Jemperli showed a 100% clinical complete response rate in a phase 2 trial, supporting its potential to improve treatment for patients with this condition.

Incidence of squamous cell anal carcinoma (SCAC) is rising; ASCO's 2024 guideline recommends concurrent chemoradiation with mitomycin-C and 5-fluorouracil or capecitabine. Retifanlimab, a checkpoint inhibitor, showed improved progression-free survival and overall survival in phase 3 trials, potentially becoming a new standard of care for SCAC. SCAC, primarily HPV-driven, remains a significant unmet medical need with no FDA-approved treatments for advanced disease.

Zejula-Jemperli combo showed 16.7% pCR and 44.4% RCB score of zero or 1 in BRCA-mutated ER+/HER2- breast cancer patients. Common severe side effects included rash, increased liver enzymes, and nausea.

Niraparib plus dostarlimab induced responses in BRCA-positive ER+/HER2- breast cancer patients, with a 16.7% pCR rate. Increased baseline sTILs associated with pathologic response. Further research on immunosuppressive tumor microenvironment needed.

Dostarlimab achieved a 100% clinical complete response rate in patients with dMMR/MSI-H advanced rectal cancer, according to a phase 2 study. The FDA granted dostarlimab breakthrough therapy designation for locally advanced dMMR/MSI-H rectal cancer treatment. No grade 3 or higher adverse events were reported, and the safety profile was consistent with previous data.

ANB032, a BTLA agonist, did not meet primary/secondary endpoints in ARISE-AD trial for atopic dermatitis; well tolerated with no safety signals. AnaptysBio to discontinue ANB032 investment, focusing on rosnilimab (PD-1+ T cell depleter/agonist) with Phase 2b RA data expected Feb 2025 and Phase 2 UC data in Q1 2026. Year-end 2024 cash estimated at $415M, extending runway to year-end 2027.

Cathy Eng, MD, FACP, FASCO, discussed biomarker testing, sequencing strategies, and clinical trial data for colorectal cancer (CRC) at the 42nd Annual Chemotherapy Foundation Symposium. Eng emphasized the importance of next-generation sequencing (NGS) and circulating tumor DNA (ctDNA) in informing treatment decisions. She highlighted data from the CheckMate-8HW and MOUNTAINEER-03 trials, and the role of immunotherapy and antibody-drug conjugates in CRC treatment. Eng also discussed the evolving use of ctDNA testing and the critical importance of NGS for all CRC patients.

2024 saw transformative advances in oncology, including improved liquid biopsy assays, AI-driven diagnostics, and expanded use of CDK4/6 inhibitors, antibody-drug conjugates, and immunotherapies. Notable approvals included ribociclib for high-risk breast cancer, T-DXd for HER2-low breast and gastric cancers, and tisotumab vedotin-tftv for cervical cancer. Molecular therapies like lazertinib and amivantamab-vmjw for NSCLC, and selpercatinib for medullary thyroid cancer, also advanced. Lifestyle interventions and metabolic therapies showed potential in improving quality of life and anticancer effects.

Experts discuss endometrial cancer treatment options based on genomic subtypes, emphasizing molecular testing, neoadjuvant strategies, and the role of chemotherapy, radiotherapy, and immunotherapy. They highlight the importance of histology and molecular classification in treatment decisions, with Westin advocating for minimally invasive surgery for low-grade tumors and more extensive imaging for higher-grade cases. The discussion also covers the use of immunotherapy in combination with chemotherapy for mismatch repair deficient tumors, and the potential of PARP inhibitors and HER2-targeted therapies in endometrial cancer treatment.

The FDA has approved MI Cancer Seek, a companion diagnostic test using whole exome and transcriptome sequencing to identify cancer patients eligible for targeted therapies, including pan-cancer and tumor-specific indications.