RAPT Therapeutics Reports Positive Initial Data from Ongoing Phase 1/2 Clinical Trial of FLX475 in Multiple Cancer Indications - Seite 2

Charged cancers are tumors that contain high levels of both regulatory T cells (T_reg) and CD8 T cells and express high levels of the ligands for CCR4.

Phase 1/2 Clinical Trial Design
The ongoing open-label Phase 1/2 study is enrolling patients with multiple types of cancer at leading cancer centers across the United States, Australia and Asia. The Phase 1 portion of the trial is focused on evaluating the safety, pharmacokinetics and pharmacodynamics of FLX475 as a monotherapy and in combination with pembrolizumab. The Phase 2 portion is designed to evaluate the degree of antitumor activity of FLX475 as a monotherapy and in combination with pembrolizumab specifically in patients with several types of charged tumors. Changes in the tumor microenvironment and other biomarkers are being evaluated in both phases of the study. For more information please visit clinicaltrials.gov identifier NCT03674567.

Phase 1 Dose Escalation Data
The dose escalation Phase 1 portion of the trial enrolled a total of 37 patients with cancers of different types. Nineteen patients were treated with one of four doses (25 mg, 50 mg, 75 mg or 100 mg once daily) of FLX475 monotherapy and 18 were treated with one of three doses (50 mg, 75 mg or 100 mg once daily) of FLX475 in combination with the standard dose of pembrolizumab. Disease control, defined as a best response of stable disease (SD), an unconfirmed or confirmed partial response (PR) or complete response (CR), was observed in 14 of the 17 evaluable monotherapy patients, including an unconfirmed partial response in a patient with relapsed metastatic cervical cancer. In the combination cohorts, disease control was observed in 13 of the 14 evaluable patients. This includes two confirmed partial responses: a patient with NSCLC who had progressed on prior checkpoint treatment (atezolizumab) and who remains on study after 18 months of treatment, and a patient with checkpoint inhibitor-naïve urothelial cancer who was on study for over nine months of treatment. In addition, preliminary data show an increase in the CD8 to T_reg ratio after treatment, which is consistent with the hypothesis that a CCR4 antagonist can block the recruitment of tumor T_reg, increase the CD8 to T_reg ratio and potentially enhance antitumor immunity.