Orphan Drug Designation Granted to Small Cell Lung Cancer Treatment, ATI-1123

The US Food and Drug Administration (FDA) granted an orphan drug designation to Cytori Therapeutics’ ATI-1123 chemotherapy drug for the treatment of small cell lung cancer (SCLC). Now, the therapy is ready to move into a phase 2 clinical trial.

Data from a phase 1 clinical trial served as the basis for the designation. The non-randomized, single-group, open-label trial included 29 patients with cervical, gastric, melanoma, non-small cell lung, ovarian, pancreatic, prostate, thyroid, urachal, and uterine cancers. A clinical benefit with ATI-1123 was demonstrated by 82% of the participants.

An improved safety profile compared to the Taxotere label—a different chemotherapy drug—was also observed for ATI-1123, which demonstrated a 31% reduction in neutropenia and anemia. A 20% increase in maximum tolerated dose as compared with standard docetaxel—a different chemotherapy drug—and signs of efficacy with 1 partial responder were also demonstrated by ATI-1123.

For the trial, patients with advanced solid malignancies were intravenously (IV) administered escalating doses of ATI-1123 over 1-h every 3 weeks. An accelerated titration design was used to begin the dosing, which was followed by a modified 3 + 3 Fibonacci schema to establish the maximally tolerated dose (MTD).

Encapsulated/non-encapsulated docetaxel was searched for in plasma, and a model independent method was used to analyze pharmacokinetics (PKs). The MTD was identified as 90 mg/m² in the expanded cohort of 10 patients.

Fatigue, nausea, neutropenia, anemia, anorexia, and diarrhea were listed as the most common adverse events associated with ATI-1123 treatment. Linear and dose proportional PKs were demonstrated by ATI-1123.

A confirmed partial response was experienced by 1 patient with lung cancer, and in 75% of patients, stable disease was observed.

Currently, the only FDA-approved agent for 2nd line treatment of SCLC is topotecan, which is associated with an overall response rate of 24%, a median response duration or time to progression of 14 weeks, and a median overall survival of 25 weeks. Treatment usually consists of a consecutive 5-day regimen of either IV or oral administration of the drug, which has black box warnings for severe myelosuppression. Topotecan is also associated with substantial morbidity, including bone marrow suppression leading to neutropenia, thrombocytopenia, and anemia requiring interventions of transfusion and growth factor support.

As no novel, major treatment advances have been developed in the last 30 years, a significant and unmet need remains for patients who are unable to tolerate the adverse effects of first-line chemo-radiotherapy and for relapsed/refractory patients who are administered topotecan.

ATI-1123 is anticipated to have less intensive administration routine and an improved side effect profile in addition to comparable or better efficacy to currently available standards with its combination of improved liposome stability, reduced toxicity, and superior delivery, according to Cytori.