Trial begins of NUV-1511 in solid tumors, including mCRPC

The first patient has been dosed in a phase 1/2 dose escalation trial of NUV-1511 in patients with advanced solid tumors, including metastatic castration-resistant prostate cancer (mCRPC), announced Nuvation Bio, the developer of the therapy, in a news release.¹

The investigational new drug application was cleared by the FDA in January 2024.

According to Nuvation, NUV-1511 is the first clinical candidate from the company’s novel drug-drug conjugate (DDC) platform, which is designed to deliver anti-cancer therapies to tumor cells and exert greater toxicity against them than against healthy tissues.²

“Dosing the first patient with NUV-1511 marks a significant milestone for our proprietary DDC platform, from which we are developing potent oncology-focused chimeric small molecules designed to selectively deliver anti-cancer therapeutics to cancer cells, while mitigating effects on healthy non-target tissues,” said David Hung, MD, the founder, president, and CEO of Nuvation Bio, in the news release.¹ “DDCs are the core technology upon which the Company was founded and we are excited to bring our first DDC clinical candidate to patients.”

The investigational new drug application was cleared by the FDA in January 2024 to initiate the launch of the current phase 1/2 study.³

Overall, the trial is designed to explore the safety, tolerability, pharmacokinetics, and preliminary clinical activity of NUV-1511 in patients with mCRPC, HER2-negative metastatic breast cancer, pancreatic cancer, and platinum-resistant ovarian cancer whose tumors have progressed following treatment with fam-trastuzumab-deruxtecan-nxki (Enhertu) and/or sacituzumab govitecan-hziy (Trodelvy). Phase 1 of the trial will explore 2 dosing schedules for NUV-1511 with the goal of establishing the recommended phase 2 dose for the next phase of the trial.

Additional studies in mCRPC

NUV-1511 is the most recent addition to the company’s investigational compounds, which also includes NUV-868, a BD2-selective oral small molecule bromodomain and extra-terminal inhibitor. Assessment of NUV-868 began with the initiation of a phase 1/2 trial (NCT05252390), with the phase 1 dose escalation portion of the study designed to explore the treatment as a monotherapy in patients with advanced solid tumors.⁴

The phase 1b portion of the study was launched in December 2022 to explore the safety and dosing of NUV-868 in combination with olaparib (Lynparza) or enzalutamide (Xtandi).⁵ The therapy in combination with olaparib will be assessed in adult patients with mCRPC, ovarian cancer, triple-negative breast cancer, pancreatic cancer, and other advanced solid tumors. The therapy in combination with enzalutamide will be assessed in adult patients with mCRPC.

Patients will be excluded from the phase 1/2 trial if they have received chemotherapy, hormonal therapy, radiation, or biological anticancer therapy 14 days prior to first treatment dose, if they have taken medications known to be strong inducers or inhibitors of CYP3A4/5 enzymes, if they are pregnant or breastfeeding, or if they have received treatment with any investigational agent within 14 or 21 days prior to first treatment dose for non-myelosuppressive agents or myelosuppressive agents, respectively.⁶

Treatment in the phase 1b study remains ongoing for both combination arms. Treatment will be administered at escalating dose levels until a recommended phase 2 combination dose level is determined. The company also noted plans for a phase 2 monotherapy study to further assess the safety and efficacy of NUV-868 in patients with mCRPC.⁴

References

1. Nuvation Bio doses first patient in phase 1/2 study of NUV-1511 for the treatment of advanced solid tumors. News release. Nuvation Bio. March 14, 2024. Accessed March 19, 2024. https://investors.nuvationbio.com/news/news-details/2024/Nuvation-Bio-Doses-First-Patient-in-Phase-12-Study-of-NUV-1511-for-the-Treatment-of-Advanced-Solid-Tumors/default.aspx

2. Pipeline. Nuvation Bio. Accessed March 19, 2024. https://www.nuvationbio.com/pipeline/

3. Nuvation Bio announced FDA clearance of investigational new drug application for NUV-1511 for the treatment of advanced solid tumors. News release. January 8, 2024. Accessed March 19, 2024. https://investors.nuvationbio.com/news/news-details/2024/Nuvation-Bio-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-NUV-1511-for-the-Treatment-of-Advanced-Solid-Tumors/default.aspx

4. Nuvation Bio announced FDA clearance of investigational new drug application for NUV-868 for the treatment of advanced solid tumors. News release. Nuvation Bio Inc. January 20, 2022. Accessed March 19, 2024. https://investors.nuvationbio.com/news/news-details/2022/Nuvation-Bio-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-NUV-868-for-the-Treatment-of-Advanced-Solid-Tumors/default.aspx

5. Nuvation Bio doses first patient in phase 1b combination study of NUV-868. News release. Nuvation Bio Inc. December 19, 2022. Accessed March 19, 2024. https://investors.nuvationbio.com/news/news-details/2022/Nuvation-Bio-Doses-First-Patient-in-Phase-1b-Combination-Study-of-NUV-868/default.aspx

6. NUV-868 as monotherapy and in combination with olaparib or enzalutamide in adult patients with advanced solid tumors. ClinicalTrials.gov. Last updated February 28, 2024. https://clinicaltrials.gov/study/NCT05252390