FDA Removes Clinical Hold From NL-201, Allowing Launch of Study in R/R Solid Tumors

The FDA has removed the clinical hold on the investigational new drug application of NL-201, a treatment for relapsed or refractory tumors, allowing a phase 1 clinical trial to begin.

The FDA has removed the clinical hold on the investigational new drug application of NL-201, a treatment for relapsed or refractory tumors, allowing a phase 1 clinical trial to begin, according to a press release by Neoleukin Therapeutics, Inc.

NL-201 IS an IL-2 AND IL-5 de novo receptor agonist that is meant to expand CD8 T cells and natural killer (NK) cells with any bias towards cells that express alpha receptor subunit (CD25). Preclinical data found that NL-201 stimulates and expands CD8+ and NK cells at low doses and minimally impacts immunosuppressive regulatory T cells. A clinical hold was placed on the agent in early January 2021 after the FDA requested that more precisely measures of the amount of protein being administered and demonstration of accurate delivery of the intended dose.

“We are pleased to have addressed the FDA’s concerns and receive clearance to proceed with our Phase 1 trial of NL-201 in the US,” said Jonathan Drachman, MD, chief executive officer, Neoleukin Therapeutics, Inc, in a press release. “We believe NL-201 represents the first de novo protein therapeutic to enter clinical development and look forward to evaluating its safety and preliminary antitumor activity in patients with advanced solid tumors.”

The planned non-randomized phase 1 study has a planned enrollment of 120 participants. It will be a first-in-human trial and has a planned competition date of December 2024. Primary outcomes include the recommended phase 2 dose of NL-201, the recommended dose schedule, incidents of treatment-emergent adverse events (TEAE), and the severity of TEAEs. Secondary outcomes include best objective response, objective response rate, progression-free survival, duration of response, pharmacokinetic profile by half-life, and under the plasma. Concentration time curve, and the immunogenicity of NL-201 with a time frame of up to 24 months. Other outcomes include flow cytometry analysis of immune cells in the blood, serum measurements of inflammatory cytokine levels, analysis of immune character of the tumor micromovement, and estimated additional measurements of anti-tumor activity of NL-201 per iRECIST criteria with a time frame of up to 36 months.

The study will be made up of 2 parts. Part 1 will be the dose-escalation portion. During this part, patients will be given NL-201 intravenously in ascending doses on 2 different schedules. During part 2, the dose-expansion cohort will be administered NL-201 at dose and schedule determined by part 1.

In order to participate, patients must have measurable disease, an ECOG performance status of 0 or 1, and must have a relapsed or refractory advanced solid tumor, other than prostate cancer, who have progressed, not tolerated, or are ineligible for all approved lines of therapy. During part 2, patients with skin cancer can participate if they have failed at least 1 line of systemic therapy. Patients with prostate cancer, any serious medical condition or laboratory abnormality, known or suspected SARS-CoV-2 infection, a history of solid organ transplant, or prior chimeric antigen receptor T-cell therapy are not eligible to participate.

Neoleukin Therapeutics announces clearance to proceed with NL-201 phase 1 clinical trial in the United States. News release. Neoleukin. April 26, 2021. Accessed April 26, 2021. https://bit.ly/3vcEOtI.