On November 3, 2023 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported safety and efficacy data from its Phase 2 trial of FLX475 (tivumecirnon) in patients with advanced non-small cell lung cancer (NSCLC) who had no prior checkpoint inhibitor therapy (Press release, RAPT Therapeutics, NOV 3, 2023, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-announces-positive-data-including-objective [SID1234636896]). The trial evaluated FLX475, an oral small molecule CCR4 antagonist designed to block the migration of regulatory T cells, in combination with the checkpoint inhibitor pembrolizumab. In this cohort of NSCLC patients, 36 patients were evaluable for efficacy, of which 20 were PD-L1 positive. In these PD-L1 positive patients, the combination of FLX475 and pembrolizumab showed a 40% (8/20) confirmed ORR and a median PFS of 6.3 months as of the data cut off date, with seven patients continuing on study. For comparison, historical pembrolizumab monotherapy activity in checkpoint inhibitor-naïve and previously-treated NSCLC patients showed a confirmed ORR of 18% and a median PFS of 4.0 months. The confirmed ORR for the combination of FLX475 and pembrolizumab in PD-L1 low and high subsets were 38% (6/16) and 50% (2/4), respectively. For comparison, the ORR for pembrolizumab monotherapy in the PD-L1 low and high subsets has been previously reported as 10% and 30%, respectively.
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The data were presented today in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting being held in San Diego. The presenting author was Julie Brahmer, M.D., Co-director of the Upper Aerodigestive Department and Professor of Oncology, Johns Hopkins University.
"We are excited by the response rates and PFS data for FLX475 in combination with a checkpoint inhibitor in this cohort of NSCLC patients. The data from this cohort, which will continue to mature and potentially improve, met our criteria to advance development of FLX475," said Brian Wong, M.D., Ph.D., President and Chief Executive Officer of RAPT. "We are particularly intrigued to see differentiating efficacy in patients with cool (PD-L1 low) tumors, which are typically poorly responsive to checkpoint inhibitors and checkpoint inhibitor combinations, such as those with anti-TIGIT antibodies. Along with RPT193, we now have two internally discovered compounds that have demonstrated clinical proof of concept in large, commercially attractive indications."
Phase 2 Data Summary in CPI-naïve NSCLC Patients (n=20)
PD-L1 Status Confirmed Responses (n) Confirmed ORR
Positive (TPS ≥1%) 8/20 40%
Low (TPS 1-49%) 6/16 38%
High (TPS ≥50%) 2/4 50%
At the time of data cut off, there was one additional response among the PD-L1 low patients awaiting confirmation.
The combination of FLX475 and pembrolizumab was well tolerated in this Phase 2 NSCLC cohort. The most common treatment-emergent adverse event deemed related to study treatment was QT prolongation that was asymptomatic and reversible. FLX475 has now been dosed in more than 300 patients with various advanced cancers and has been generally well tolerated, and the combination with pembrolizumab has not increased immune-related toxicity beyond that expected with pembrolizumab alone.
In previous disclosures, FLX475 showed durable objective responses as monotherapy in an EBV+ lymphoma, as well as in combination with pembrolizumab in EBV+ gastric cancer.
Webcast Conference Call Information
RAPT will host a webcast conference call today, November 3, 2023 at 10:00 a.m. PT. To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the RAPT Therapeutics website at https://investors.rapt.com/events-and-presentations.
About FLX475
FLX475 (tivumecirnon) is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues. Treg represent a dominant pathway for downregulating the immune response, generally correlate with poor clinical outcomes, and may limit the effectiveness of currently available therapies such as checkpoint inhibitors. FLX475 may restore naturally occurring antitumor immunity alone and may synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators, cancer vaccines, and adoptive T cell therapy.