Phase 1/2 trial launches of molecular glue degrader for ccRCC

The first patient has been dosed in a phase 1/2 trial (NCT07300241) of NEO-811, an investigational molecular glue degrader being evaluated for locally advanced or metastatic nonresectable clear cell renal cell carcinoma (ccRCC).¹

“NEO-811 is a novel, potent, cereblon-dependent, and selective molecular glue degrader designed to fully block a key signaling pathway in clear cell renal cell cancer,” said Toni K. Choueiri, MD, chair of the study steering committee, in a news release from the drug’s developer, Neomorph, Inc.¹ “The unique mechanism of action of NEO-811 is quite promising and could offer a new treatment option for patients.”

Choueiri is director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, coleader of the Kidney Cancer Program at Dana-Farber/Harvard Cancer Center, and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School.

The open-label, first-in-human study is designed to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of NEO-811 in this patient population.² The study will consist of a single-agent dose-escalation phase, followed by a dose-expansion phase.¹

Trial investigators plan to enroll up to 30 patients with locally advanced or metastatic nonresectable ccRCC who progressed on standard therapies. The study is enrolling patients through clinical trial sites across the US.

To be eligible for enrollment, patients must have measurable disease per RECIST version 1.1; an ECOG performance status of 0 or 1; adequate hematologic, hepatic, and renal function; and newly obtained or archival formalin-fixed paraffin-embedded tumor tissue. Patients are not eligible if they have predominantly non–clear cell RCC histologic subtypes; leptomeningeal disease or symptomatic active central nervous system (CNS) metastases (with exceptions for asymptomatic treated CNS metastases, per protocol); or a history of hepatitis B virus, hepatitis C virus, or HIV infection.²

The primary outcome measures for phase 1 of the study are the frequency and severity of treatment-emergent adverse events as well as the determination of a maximum tolerated dose and/or recommended phase 2 dose of NEO-811 monotherapy. The study will also assess preliminary tumor responses and other pharmacokinetic measures. Primary completion of the study is expected in January 2027, with final completion slated for September 2027.²

“Dosing the first patient in our phase 1/2 trial of NEO-811 in renal cell carcinoma marks a pivotal inflection point for Neomorph, representing the first clinical evaluation of an asset from our internally developed pipeline,” said Phil Chamberlain, DPhil, cofounder, president, and CEO of Neomorph, in the news release.¹ “As we advance in the clinic, we look forward to generating data that will inform the continued development of NEO-811 and further validate the potential of our platform to deliver differentiated medicines for patients with significant unmet need.”

REFERENCES

1. Neomorph announces first patient dosed in phase 1/2 trial evaluating NEO-811 for the treatment of locally advanced or metastatic non-resectable clear cell renal cell carcinoma. News release. Neomorph Inc. February 3, 2026. Accessed February 5, 2026. https://www.globenewswire.com/news-release/2026/02/03/3231475/0/en/Neomorph-Announces-First-Patient-Dosed-in-Phase-1-2-Trial-Evaluating-NEO-811-For-the-Treatment-of-Locally-Advanced-or-Metastatic-Non-Resectable-Clear-Cell-Renal-Cell-Carcinoma.html

2. Open-label phase 1/​2 study of NEO-811 in subjects with locally advanced or metastatic non-resectable clear cell renal cell carcinoma. ClinicalTrials.gov. Updated January 14, 2026. Accessed February 5, 2026. https://clinicaltrials.gov/study/NCT07300241