On June 4, 2021 Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, reported that positive interim clinical data from the dose escalation portion of its first-in-human Phase 1 trial evaluating RBN-2397, a small molecule inhibitor of PARP7, as a monotherapy in patients with advanced solid tumors (Press release, Ribon Therapeutics, JUN 4, 2021, View Source [SID1234583556]). Presenting the data in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4, 2021, will be Gerald S. Falchook, M.D., Director, Drug Development, Sarah Cannon Research Institute at HealthONE, Denver, CO and Clinical Investigator in the RBN-2397 Phase 1 trial.
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"We are pleased to see demonstration of target inhibition and preliminary signs of antitumor activity in this early stage of clinical development of a novel target," said Dr. Falchook. "In the expansion part of the study, we will seek to demonstrate definitive clinical activity in tumor types predicted to respond to RBN-2397."
The primary objectives of the study are to determine any dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and establish the recommended phase 2 dose (RP2D). The dose escalation portion evaluated two dosing schedules with multiple ascending dose cohorts of RBN-2397. As of April 1, 2021, the dose escalation portion of the study, in which 50 patients were enrolled, is complete and the key results are as follows:
Single-agent RBN-2397 was well-tolerated at exposures predicted to be efficacious in preclinical studies
RP2D was 200 mg BID on a continuous dosing schedule
In this heavily pretreated, heterogenous patient population, preliminary antitumor activity was observed with one partial response (PR) in a patient with HR+ breast cancer and nine patients with stable disease (SD) > 4 months
Includes one patient with squamous cell carcinoma of lung (SCCL) who has been on study with SD for 17+ months and 29% tumor shrinkage post data cutoff date and a second SCCL patient with SD for 4+ months and 19% tumor shrinkage
Proof of mechanism demonstrated by increase in tumoral Type I interferon (IFN) response and immune cells after treatment with RBN-2397
Expansion phase is currently enrolling patients in a number of defined cohorts, including SCCL
"These results validate our approach to drug development by targeting cellular stress and modulating the immune system to induce antitumor activity," said Sudha Parasuraman, M.D., Chief Medical Officer, Ribon Therapeutics. "We expect the expansion part of the study to establish proof of concept for RBN-2397 monotherapy and look forward to expanding our development program with the initiation of a Phase 1b/2 combination study with pembrolizumab in SCCL in the second half of 2021."
About RBN-2397
RBN-2397 is an orally available small molecule inhibitor of PARP7 that Ribon Therapeutics is developing for the treatment of solid tumors. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors (NCT04053673). PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.