New Evidence of Monotherapy and Combination Activity in Charged Tumor Types

RAPT Therapeutics FLX475 is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors
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(Vax Before Cancer)

A California immunology-based biopharmaceutical company announced positive initial clinical data from its ongoing Phase 1/2 trial for FLX475 in multiple cancer indications.

FLX475 is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues.

RAPT Therapeutics, Inc.’s initial observations as of November 10, 2020, from the ongoing trial for FLX475, include preliminary evidence of monotherapy activity, encouraging efficacy in combination with the PD-1 checkpoint inhibitor pembrolizumab (marketed as Keytruda®) and biomarker data supporting FLX475’s mechanism of action.

In addition, FLX475 demonstrated a favorable safety profile, both as monotherapy and in combination with pembrolizumab.

“We are pleased with the early evidence of clinical activity of FLX475, both as monotherapy and in combination with pembrolizumab in multiple charged tumor types,” said Brian Wong, M.D., Ph.D., President and CEO of RAPT, in a press release. 

“Based on these encouraging data, we have determined that three cancer indications, EBV+ lymphoma, nasopharyngeal cancer, and head and neck cancer, have generated sufficient early evidence of efficacy to advance into expanded Phase 2 evaluation. We continue to enroll patients and generate data in this multi-cohort, multi-indication trial and look forward to providing updates on all remaining cohorts and additional go-forward decisions next year.”

Scott Antonia, M.D., PhD., Professor of Medicine and Director of the Duke Cancer Institute Center for Cancer Immunotherapy and a member of RAPT’s Scientific Advisory Board, added, “FLX475 is a potent non-depleting CCR4 antagonist that is designed to block regulatory T cells that interfere with an effective anti-tumor immune response.” 

“These data are particularly impressive as the immunotherapy field has long recognized Treg as important targets in oncology, but until FLX475, others have not been able to selectively target these cells in the tumor microenvironment without affecting beneficial cells.  These data demonstrate that RAPT’s oral small molecule approach with FLX475 holds promise in treating a variety of charged cancers.”

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

Based on the promising early results from the Phase 1/2 trial with FLX475 observed to date, RAPT has selected (3) cancer indications for expansion:  

  • EBV+ lymphoma – Early data from the first two patients with EBV+ lymphoma treated with FLX475 monotherapy show significant target tumor reduction, including one patient (1/2) who achieved a durable complete metabolic response and continues on study after more than nine months. RAPT plans to expand the EBV+ lymphoma monotherapy cohort and initiate a separate expansion cohort in EBV+ lymphoma in combination with pembrolizumab.
  • Checkpoint inhibitor-naïve nasopharyngeal cancer (NPC) – Of the 10 evaluable patients with NPC treated with FLX475 monotherapy, seven of 10 (7/10) patients exhibited stable disease as best response. Seven of the 10 patients crossed over to combination therapy where significant clinical activity has been observed. Of the six evaluable patients who crossed over, five were checkpoint inhibitor naïve. All five (5/5) of the checkpoint inhibitor-naïve patients demonstrated significant tumor shrinkage, with three (3/5) of these patients showing a partial response (two confirmed and one unconfirmed). Based on these results, RAPT plans to open a combination cohort in checkpoint inhibitor-naïve NPC.
  • Checkpoint inhibitor-naïve head and neck cancer – Of the 10 evaluable patients with head and neck cancers treated with FLX475 monotherapy, five of 10 (5/10) patients exhibited stable disease as best response. Six patients initially treated with monotherapy crossed over to combination therapy, with one achieving a partial response and a second patient with an unconfirmed partial response (2/6). Seventeen patients are enrolled in a separate combination treatment cohort, of which 10 are evaluable so far. Substantial tumor reduction has been observed in four of the 10 (4/10), including one confirmed complete response and three patients with greater than 20 percent tumor reduction. Based on these results, RAPT plans to expand the combination cohort in checkpoint inhibitor-naïve head and neck cancers.

RAPT Therapeutics is a clinical-stage immunology-based biopharmaceutical company focused on discovering, developing, and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases.

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