Emerging Therapies

Improving clinical outcomes in the second line of treatment in patients with advanced biliary tract cancer remains an important goal, and researchers have been exploring various therapeutic targets, including HER2, an oncogene that creates a protein that encourages cell growth and accelerates the spread of cancers.

During the 2023 American Association for Cancer Research Annual Meeting, researchers presented results from a phase 2b clinical trial demonstrating significant improvement in recurrence-free survival in patients with high-risk melanoma who were treated with a combination of an investigational personalized mRNA-based vaccine plus the immune checkpoint inhibitor pembrolizumab (Keytruda), compared with pembrolizumab alone.

Single-agent mosunetuzumab is a safe and clinically promising chemotherapy-free therapy for elderly and unfit patients with untreated diffuse large B-cell lymphoma (DLBCL), said Adam J. Olszewski, MD, Associate Professor of Medicine, Brown University, Providence, RI, at ASH 2020. Dr Olszewski reported the results of a phase 1/2 clinical study of mosunetuzumab in patients with DLBCL.

Results of a phase 1 clinical trial showed that approximately 66% of patients with chronic-phase chronic myeloid leukemia (CML) had a major cytogenetic response (MCyR) to the novel oral BCR-ABL1 tyrosine kinase inhibitor (TKI) vodobatinib, regardless of whether they previously received ponatinib therapy. Jorge E. Cortes, MD, Director, Georgia Cancer Center, Augusta University, presented the results at ASH 2020.

Magrolimab, a first-in-class investigational antibody targeting CD47, showed good efficacy when combined with azacitidine injection (Vidaza) regardless of TP53 mutation in patients with treatment-naïve acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, according to data presented at ASH 2020. The results also showed that this combination did not lead to significant immune-related side effects.

The selective, oral retinoic acid receptor alpha (RARA) agonist, SY-1425, combined with azacitidine showed encouraging activity in patients with relapsed or refractory acute myeloid leukemia (AML) that is overexpressing the RARA gene in a phase 2 clinical trial presented at ASH 2020. The RARA gene is a novel target in patients with AML.

Sotorasib, an investigational small-molecule inhibitor of the KRAS p.G12C mutation, demonstrated promising activity and encouraging safety in patients with advanced solid tumors, in particular those with non–small-cell lung cancer (NSCLC), in the preliminary phase 1 CodeBreaK 100 trial. The findings were presented at the 2020 virtual meeting of the European Society for Medical Oncology (ESMO) and were recently published.

VS-6766, a unique inhibitor of the RAF/MEK-signaling pathway, has shown antitumor activity in RAS/RAF mutation–positive solid tumors and in multiple myeloma, when administered on an intermittent dosing schedule, according to recently published data.

Xevinapant, an investigational antagonist of IAPs (inhibitor of apoptosis proteins), prolonged overall survival (OS) in patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) when added to chemoradiotherapy, according to an updated analysis of a phase 2 clinical trial that was presented at the 2020 European Society for Medical Oncology (ESMO) congress.

A single infusion of the investigational agent lifileucel—an immunotherapy using cryopreserved autologous tumor-infiltrating lymphocytes (TIL)—induced responses in more than 33% of patients with advanced melanoma whose disease progressed with multiple previous therapies, including PD-1 and BRAF/MEK inhibitors.