SynDevRx, Inc., a clinical-stage oncology company, has submitted results of its Phase 1 dose escalation safety study in late-stage cancer patients with progressive, metastatic solid tumors to the United States Food and Drug Administration (FDA) . The study’s primary endpoint was to establish the maximum tolerated dose and dosing schedule and the recommended Phase 2 dose for SDX-7320, the company’s lead drug candidate for the treatment of metabolically sensitive cancers . Secondary and exploratory endpoints included analysis of anti-tumor efficacy and changes in key angiogenic and metabolic biomarkers.
The study evaluated data from 32 patients, whose disease progression and new lesion formation were measured at intervals of every 2 months from the initiation of treatment. Exploratory changes from baseline to metabolic hormones were measured, including leptin and adiponectin, as well as changes to insulin levels and insulin sensitivity (HOMA-IR). Exploratory changes from baseline to angiogenesis biomarkers bFGF, VEGF, and IGF-1 were also evaluated. A total of 28 patients had at least one tumor burden assessment performed, of whom 21 (75%) had at least one stable disease determination before leaving the study or experiencing progressive disease. Of these 21 patients, the period of measurable stable disease averaged 85 days. There were no objective partial or complete responses.
“The results of our Phase 1 trial suggest that SDX-7320 may have potent anti-angiogenic activity, appears to induce favorable changes to insulin, leptin and adiponectin, and has a safety profile that supports future combination studies. These data provide us with the scientific rationale for future clinical studies in tumors that are sensitive to metabolic hormones, i.e., metabo-oncology,” said Brad Carver, President and CEO of SynDevRx. “Animal data we previously presented at the San Antonio Breast Cancer Symposium in 2019 showed that SDX-7320 attenuated the hyperglycemia and hyperinsulinemia caused by the PI3K inhibitor alpelisib, and showed synergistic tumor growth inhibition in mice. Considering the aforementioned data together with this clinical data, we believe SDX-7320 could provide real benefit to breast cancer patients taking a PI3K inhibitor. We expect to open enrollment for our upcoming clinical trial in metastatic ER+/Her2- breast cancer patients with a mutation in the PIK3CA gene early next year, followed by additional trials focused on triple-negative breast cancer and prostate cancer, tumor types that are highly sensitive to systemic metabolic dysfunction.”
About the Study:
SynDevRx’s Phase 1 dose escalation study was designed to assess the safety and tolerability of SDX-7320 in patients with advanced refractory or late-stage solid tumors (lung, colon, breast, rectal, pancreatic, appendiceal, carcinoid, cholangiocarcinoma, cervical, endometrial, hepatocellular, and urothelial cancers).  Patients were a mean age of 66 years old and had progressed following five prior lines of treatment for their metastatic disease, on average.
SDX-7320 was administered subcutaneously at doses ranging from 1.7–65 mg/m2 and induced primarily mild side effects including fatigue, GI symptoms (nausea, abdominal pain, diarrhea), and anemia. The dose-limiting toxicity event, thrombocytopenia, was generally reversible without intervention and was observed only at the highest doses tested. Results of the study suggest that the dose of SDX-7320 at 49 mg/m2 on a once every two weeks (i.e., Q14D) schedule may be appropriate for future studies. 
SDX-7320 acts by inhibiting MetAP2, a clinically validated target that appears to play a key role in tumor growth, metastasis, angiogenesis, and metabolic dysfunction. “Many solid tumor types are highly sensitive to dysregulated metabolic hormones, such as insulin, leptin, or adiponectin. These hormones signal through known oncogenic pathways, like PI3K/Akt/mTOR or STAT3. Given the epidemic of metabolic syndrome in the world plus the frequency of tumors that are sensitive to metabolic hormones (e.g., breast and prostate cancers), we believe that SDX-7320 could help clinical oncologists treat their cancer patients with concomitant, systemic metabolic dysfunction in combination with standard-of-care therapies,” said James Shanahan, Co-Founder and Chief Business Officer of SynDevRx.
SynDevRx believes that SDX-7320 is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. SDX-7320 acts by binding irreversibly to the target enzyme MetAP2, triggering improvements in the metabolic hormones, insulin, leptin and adiponectin. Additionally, SDX-7320 inhibits the important angiogenic proteins bFGF and VEGF, and in preclinical studies, inhibited multiple cell cycle signaling pathways and reversed immune suppression within the tumor micro-environment. SDX-7320 is being developed for use in combination with clinically indicated standard-of-care cancer therapies.