Savolitinib (AZD6094, HMPL-504) has been demonstrated to inhibit the growth of tumors in a series of preclinical disease models, selectively for those tumors with aberrant c-Met signaling. Phase I dose escalation studies were initiated in Australia and China in 2012 and 2013 respectively. Savolitinib has demonstrated good safety and tolerability and favorable pharmacokinetic properties in late stage cancer patients, and has shown encouraging anti-tumor activity in several tumor-types, in particular for metastatic Papillary Renal Cell Cancer (PRCC). Phase II, study designed to evaluate the efficacy and safety of savolitinib in patients with locally advanced or metastatic PRCC. Approximately 20 centers in the United States, Canada, and Europe will participate in the study. The primary objective of this study is to assess the anti-tumor activity in patients with PRCC as measured by overall response rate according to Response Evaluation Criteria in Solid Tumours (“RECIST”). The secondary objectives for this study are to: assess the progression free survival and duration of response in patients with PRCC according to RECIST; assess the safety and tolerability in the treatment of patients with PRCC; characterize the pharmacokinetics and pharmacodynamics of savolitinib and metabolites following administration to steady state after multiple dosing when given orally.

Sulfatinib (previously known as HMPL-012) was developed as a small-molecule inhibitor targeting vascular endothelial growth factor receptors 1 and 3, fibroblast growth factor receptor 1 and colony-stimulating factor 1 receptor with potential antineoplastic and anti-angiogenic activities. Sulfatinib has shown encouraging antitumor activity and manageable toxicities in patients with advanced neuroendocrine tumors (NET). The drug is participating in two ongoing phases III studies, validating the efficacy of surufatinib in patients with NETs. In addition, in November 2018, Hutchison MediPharma completed a phase II trial of sulfatinib, for the treatment of patients with biliary tract cancer. This drug is also participating in the phase II trial that is currently in recruiting status in treating advanced medullary thyroid carcinoma.

AZD 9496 was discovered by AstraZeneca as a potent and selective estrogen receptor downregulator (SERD). This drug participated in phase I clinical trials to evaluate the pharmacokinetic profiles and the safety and tolerability of the different forms, formulations, and doses for the treatment of patients with breast cancer.

TAK-733 had been developed by Millennium Pharmaceuticals (subsidiary of Takeda) for the treatment of adult patients with advanced non-hematological malignancies. In 2015, Takeda discontinued this studies. TAK-733 is an inhibitor of MEK that exhibits anticancer chemotherapeutic activity. In tumor explant models, TAK-733 induces tumor regression. In colorectal cancer cells and melanoma cells, this compound suppresses cell growth. Additionally, TAK-733 decreases tumor growth and weight in animal models of lung cancer and melanoma.

PM-00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. PM-00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. Immunohistochemical studies in tumors also demonstrated histone-H2AX phosphorylation and p53 overexpression. PM-00104 has progressed into phase II clinical trials to treat Ewing sarcoma, urothelial carcinoma, multiple myeloma, endometrial and cervical cancer. The phase II study concluded that there were no objective responses in the cohort of 16 evaluable patients with Ewing sarcoma. The study of Urothelial carcinoma treatment was terminated early because there seemed to be no benefit from the current therapy. Moreover, PM-00104 as a single-agent did not prove to be an effective therapy for patients with advanced/metastatic endometrial or cervical cancer. None achieved objective tumor response was in phase II study for the treatment of advanced/metastatic endometrial or cervical cancer. Preliminary data showed PM-00104 to be safe to use in the treatment of multiple myeloma but the complete results from this trial have not been published.

G-0853 (also GDC-0853, or Fenebrutinib) is a potent, selective, orally administered, and noncovalent Bruton's tyrosine kinase (Btk) inhibitor currently in clinical development. Upon administration, G-0853 inhibits the activity of Btk and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and Btk-mediated activation of downstream survival pathways, which leads to the inhibition of the growth of malignant B-cells that overexpress BTK. BTK is overexpressed in B-cell malignancies, and plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival. G-0853 suppresses B cell- and myeloid cell-mediated components of disease and demonstrates dose-dependent activity in an in vivo rat model of inflammatory arthritis. G-0853 demonstrates highly favorable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria.

Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

EW-7197 is an orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. EW-7197 is in phase I clinical trials for the treatment of solid tumors. Also, EW-7197 has a strong potential as an anti-fibrosis therapeutic agent.

Zorbamycin (U-30,604E), an antibiotic that induced rapid degradation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in Bacillus subtilis cells. It was shown that this drug somehow induced a change in the structure or function of the cellular DNA fraction which resulted in rapid breakdown of this fraction. Zorbamycin also possesses antitumor activity.