FDA Clears Novel Cancer Immunotherapy R-5780 for Early-Stage Trial

• The FDA has accepted the investigational new drug (IND) application to proceed with a phase 1 clinical trial of R-5780 in patients with cancer.
• R-5780 is an orally delivered immune oncology drug candidate that has previously shown the ability to engage immune pathways that enhance the effectiveness of immune checkpoint inhibitor therapy.
• The phase 1 clinical trial (NCT06398418) of R-5780 plans to assess the agent’s safety, drug exposure, and clinical activity in up to 33 participants.

The FDA has cleared the IND of R-5780, allowing for the initiation of a phase 1 trial to evaluate the agent in patients with cancer.¹

R-5780 is an orally administered immune oncology therapeutic that currently is in development for cancer treatment. R-5780 has shown significant potential to activate immune pathways that augment the effectiveness of immune checkpoint inhibitors. The agent also leverages emerging insights into gut-regulated immune mechanisms to enhance the efficacy of immuno-oncology treatments.¹

Further, R-5780 represents a precision-engineered synthetic biology approach, targeting specific immune pathways to drive a strong antitumor T-cell response. This immune oncology drug candidate is among the first of its kind and offers a novel mechanism of action with promising potential in cancer therapy.

"The FDA's clearance for R-5780 is a testament to the innovation and dedication of our team at Rise Therapeutics driving novel immunotherapies forward into human proof-of-concept" states Christian Furlan Freguia, senior vice president of research at Rise Therapeutics, in a press release. "R-5780 represents a pioneering approach that leverages the power of gut-regulated immune pathways to enhance the effectiveness of immune checkpoint inhibitors.... We believe R-5780 has the potential to expand responses in patients that become refractory to immune checkpoint inhibitors and increase responsiveness in tumors initially unresponsive to these medications".

DNA helix enlarged model in bright colors and spots: © Radomir Jovanovic - stock.adobe.com

In this phase 1 trial, patients will receive [R-5780] orally and provide patient-reported overall feeling and physician-scored measure of their tumors. Investigators will also measure blood and fecal evaluations of inflammation and assessment of R-5780 on fecal levels.²

Patients between the ages of 18 and 80 are eligible for enrollment in the study if they have unresectable stage III or stage IV melanoma, basal cell carcinoma, or squamous cell carcinoma, regardless of BRAF mutation status and other solid tumors. Additional enrollment criteria requires patients to be refractory to anti–PD-1/L1 therapy per RECIST v1.1, defined as having disease progression after receiving at least 2 complete cycles of immune checkpoint inhibitor (ICI) therapy or disease progression 6 months from initiation of ICI therapy while still on active therapy, a life expectancy of over 3 months, and an ECOG performance status of 0, 1, or 2. Patients must also have disease that is evaluable by CT or MRI per RECIST 1.1 criteria or clinically apparent disease that the investigator can follow for response.

The primary end point of the study is to determine the incidence and severity of adverse events and their relationship to R-5780 administration at baseline through week 4. The secondary end point of the study is to assess quality of life scores from baseline through the end of study day 112.

REFERENCES

1. Rise Therapeutics receives FDA IND clearance to initiate clinical testing of R-5780 in cancer. News release. Rise Therapeutics. January 13, 2025. Accessed January 13, 2025. https://tinyurl.com/2a3zbuj8

2. R-5780-01 in combination with PD-1 checkpoint inhibitors (checkpoint protein on immune cells called T cells) in patients with solid tumors. ClinicalTrials.gov. Updated November 13, 2024. Accessed January 13, 2025. https://clinicaltrials.gov/study/NCT06398418