Combination Therapy

Johnson & Johnson’s amivantamab combined with chemotherapy shows promising results in metastatic colorectal cancer. The bispecific antibody, targeting EGFR and MET, achieved a 51% overall response rate in RAS/BRAF wild-type patients. Longer-term data indicate sustained efficacy, with over 70% response in the first-line setting and durable responses exceeding two years. The combination also demonstrated activity in patients with liver metastases, with a 57% ORR. The safety profile was consistent with prior studies, with low discontinuation rates.

HUTCHMED has advanced its pancreatic cancer program to Phase III, initiating a trial for a combination therapy of surufatinib, camrelizumab, nab-paclitaxel, and gemcitabine (S+C+AG) for metastatic PDAC in China. Promising Phase II results showed significant improvements in progression-free survival and objective response rate compared to the standard chemotherapy regimen. The Phase III trial will evaluate overall survival as the primary endpoint in approximately 400 additional patients.

At ESMO 2025, Kura Oncology presented early data on farnesyl transferase inhibitors (FTIs) darlifarnib and tipifarnib. Darlifarnib monotherapy showed on-target activity in HRAS-mutant tumors. Darlifarnib combined with cabozantinib yielded a 33-50% ORR in renal cell carcinoma. Tipifarnib with alpelisib achieved a 47% ORR in heavily pretreated PIK3CA-altered head and neck cancer. These preliminary results suggest FTIs can enhance targeted therapies by addressing resistance mechanisms. Further studies are ongoing to determine optimal dosing and durability.