
[3-D model of adagrasib molecule from PubChem]
In this feature, we round up a variety of oncology drug candidates that may prove to be promising cancer therapeutics in the coming years.
1. Adagrasib
Adagrasib from Mirati Therapeutics is a KRASG12C inhibitor. In 2021, the drug candidate won Breakthrough Therapy Designation for patients with advanced non-small cell lung cancer (NSCLC) with the KRASG12C mutation. The KRAS protein inhibitor has been the subject of 14 trials to date, including a Phase 3 study focused on colorectal cancer. Adagrisib was the focus of a July 14, 2022 NEJM article, which concluded that adagrasib showed clinical efficacy in patients with previously treated KRASG12C-mutated NSCLC without any new safety signals. In February, Mirati announced that FDA had accepted the New Drug Application (NDA) for adagrasib for small cell lung cancer (NSCLC) with the KRASG12C mutation. The potential indication would cover patients who had received at least one prior systemic therapy. The Prescription Drug User Fee Action (PDUFA) date for the compound is December 14, 2022.
2. Elacestrant

[3-D model of Elacestrant from PubChem]
3. Elranatamab
Elranatamab from Pfizer (NYSE:PFE) is B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody. Elranatamab has won Orphan Drug Designations from the FDA and the European Medicines Agency (EMA) for the treatment of multiple myeloma. The FDA has also granted elranatamab Fast Track Designation and for patients with MM who are refractory to at least one proteasome inhibitor, one immunomodulatory drug and one anti-CD38 antibody.
4. Magrolimab
Magrolimab from Gilead Sciences (Nasdaq:GILD) is a potential therapy for lymphoma and multiple myeloma (MM). Earlier this year, FDA lifted a partial clinical hold on magrolimab studies after reviewing safety data from a magrolimab lymphoma study. FDA granted magrolimab Breakthrough Therapy designation for treating newly diagnosed myelodysplastic syndrome (MDS) in 2020. Gilead is also developing the drug for acute myeloid leukemia (AML) and several hematologic cancers and solid tumor malignancies. Magrolimab was featured in a 2021 roundup of antibodies to watch from the peer-reviewed journal mAbs
5. Orelabrutinib

[3-D model of Orelabrutinib from PubChem]
6. Patritumab deruxtecan

[2-D model of deruxtecan from Pubchem]
7. Pirtobrutinib
Pirtobrutinib (LOXO-305) from Loxo Oncology and Lilly (NYSE:LLY) is an investigational, oral, highly selective, reversible (noncovalent) Bruton tyrosine kinase (BTK) inhibitor. The drug candidate has shown promise in preclinical studies to reversibly bind BTK. Investigators are investigating pirtobrutinib (LOXO-305) in clinical trials focused on chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma and non-Hodgkin’s lymphoma.
8. Poziotinib

[3-D model of poziotinib image courtesy of Pubchem]
9. Tislelizumab
Tislelizumab originally developed by BeiGene, is a humanized monoclonal antibody directed against PD-1. Novartis (NYSE:NVS) has licensed the drug in most major markets. In June, Novartis announced that the antibody plus chemotherapy improved overall survival as a first-line treatment for adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in the Phase 3 RATIONALE 306 study. Novartis noticed that, in the Phase 3 study, investigators saw benefits in patients regardless of PD-L1 status.
10. Ublituximab
The immunomodulator ublituximab from TG Therapeutics is an experimental glycoengineered monoclonal antibody targeting an epitope on CD20-expressing B-cells. TG Therapeutics is pursuing indications for the drug for lymphoma and leukemia. The drug candidate also fared well in relapsing multiple sclerosis studies, including the Phase 3 ULTIMATE I (NCT03277261) and II (NCT03277248) trials. The drug was recently profiled in The New England Journal of Medicine.
Filed Under: clinical trials, Drug Discovery, Oncology