FDA greenlights phase 1 trial of NSD2 inhibitor in mCRPC

The FDA has granted clearance to the phase 1 STRIKE-001 trial (NCT07103018)evaluating KTX-2001, an oral inhibitor of nuclear receptor-binding SET domain protein 2 (NSD2) for patients with metastatic castration-resistant prostate cancer (mCRPC), K36 Therapeutics announced in a news release.¹

The company also reported that they have entered into a clinical trial collaboration with Bayer, who will provide darolutamide (Nubeqa) for the trial. KTX-2001 will be assessed both as a monotherapy and in combination with darolutamide in the study.

"We are proud to announce the FDA cleared the [investigational new drug application] for our second clinical program, KTX-2001, on July 3rd. This achievement demonstrates our team's efficiency and focus on advancing KTX-2001 and positively impacting the lives of patients with mCRPC," said Terry Connolly, PhD, president and CEO of K36, in the news release.¹ "Along with this significant milestone, I am delighted to announce the company has entered into a clinical trial collaboration agreement with Bayer for supply of darolutamide for the combination with KTX-2001 in our trial."

The phase 1 STRIKE-001 trial will be operationalized by the Prostate Cancer Clinical Trials Consortium (PCCTC), which has been selected as the Contract Research Organization by K36 Therapeutics.

According to K36, enrollment for the phase 1 trial is set to begin in the second half of 2025.

In total, the multicenter, open-label trial plans to enroll 144 male patients with mCRPC across clinical trial sites in the US.² To be eligible forenrollment, patients must have an ECOG score of 0 or 1; metastatic disease per bone scan, CT, or MRI; and adequate renal, hepatic, and hematological function. Further, all patients enrolled in the study must have progressed following prior treatment with an androgen receptor pathway inhibitor (abiraterone [Zytiga], enzalutamide [Xtandi], darolutamide [Nubeqa], or apalutamide [Erleada]).

The trial will be conducted in 2 parts. In part A, patients will receive escalating doses of KTX-2001 monotherapy to assess the safety, tolerability, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) level(s) of the agent. Part B of the study will assess the safety and tolerability of escalating dose levels of KTX-2001 in combination with darolutamide to further determine the RP2D.

The primary outcome measure is the percentage of patients with dose-limiting toxicities to determine the MTD. Pharmacokinetics, pharmacodynamics, and preliminary clinical activity of KTX-2001 will also be assessed in both parts of the trial.

Primary completion of the study is anticipated for September 2027.

KTX-2001 marks K36 Therapeutics’ second NSD2 inhibitor to enter phase 1 development. Their first agent, KTX-1001, is currently being assessed in a phase 1 study (NCT05651932) for the treatment of patients with relapsed and/or refractory multiple myeloma with genetic translocation t(4;14).

"Targeting NSD2 inhibition as a first-in-class, oral therapy represents a fundamentally new approach to treating prostate cancer by modulating the epigenetic drivers of tumor progression. This novel mechanism is distinct from other epigenetic therapies and addresses the underlying biology in a new way,” concluded Jason Redman, MD, senior medical director at K36 Therapeutics and leader of the KTX-2001 prostate cancer program, in the news release.¹ “The STRIKE-001 phase 1 trial marks an important step forward, bringing a promising new option to patients with limited treatment alternatives."

REFERENCES

1. K36 Therapeutics receives FDA Clearance of investigational new drug (IND) application for KTX-2001 in metastatic castration-resistant prostate cancer (mCRPC) and announces clinical trial collaboration with Bayer for supply of darolutamide. News release. K36 Therapeutics. August 7, 2025. Accessed August 7, 2025. https://www.prnewswire.com/news-releases/k36-therapeutics-receives-fda-clearance-of-investigational-new-drug-ind-application-for-ktx-2001-in-metastatic-castration-resistant-prostate-cancer-mcrpc-and-announces-clinical-trial-collaboration-with-bayer-for-supply-of-daro-302523702.html

2. A clinical study of KTX-2001 in subjects with metastatic castration-resistant prostate cancer (STRIKE-001) (STRIKE-001). ClinicalTrials.gov. Last updated August 5, 2025. Accessed August 7, 2025. https://clinicaltrials.gov/study/NCT07103018