FDA Gives Fast Track Designation to LYT-200 in Advanced Head and Neck Cancers

LYT-200 is a human IgG4 monoclonal antibody designed to target galectin-9 for those with locally advanced or metastatic solid tumors.

The FDA has granted fast track designation to LYT-200 plus a PD-1 inhibitor as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma, according to a press release from PureTech Health, the developer of LYT-200.¹

The acceptance was based on the results of a phase 1/2 trial (NCT04666688) assessing LYT-200 monotherapy or with chemotherapy and tislelizumab-jsgr (Tevimbra) for patients with locally advanced or metastatic solid tumors.² Of note, safety was favorable in all cohorts including the monotherapy and combination ones, and patients had disease control with a suggestion of antitumor activity.

"In the [United States], there are approximately 66,000 people diagnosed with head and neck cancers each year, and the prognosis for metastatic disease is unfavorable, with a median survival rate of about 10 months," said Eric Sherman, MD, a head and neck oncologist from Memorial Sloan Kettering Cancer Center and an investigator on the trial. "There is an important need to explore promising new mechanisms and targets such as galectin-9 to bring therapeutic innovation to this patient population."

LYT-200 is a human IgG4 monoclonal antibody designed to target galectin-9 for those with locally advanced or metastatic solid tumors. Those with this disease often have poor survival rates. This treatment is also being evaluated for those with hematologic malignancies, specifically acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To date, LYT-200 is the most potent clinical program against galectin-9.

Investigators have found that LYT-200 has previously shown direct cytotoxic and anti-leukemic events through multiple mechanisms and has shown a cohesiveness with standard chemotherapy and venetoclax (Venclexta).

Currently, a phase 1b trial (NCT05829226) is underway assessing LYT-200 monotherapy and LYT-200 plus venetoclax and a hypomethylating agent for patients with AML and MDS. The most recent data have shown favorable safety and tolerability as well as potential clinical activity.

An estimated 80 patients are expected to enroll in the phase 1/2 trial for solid tumors. Part 1 will include the single agent in a dose=escalation design using a continuous reassessment method and a combination portion using a 4+2 design. In part 2, the dose-expansion portion will look at specific disease indications based on results from part 1.

The arm for part 1 will include single-dose LYT-200, and the combination arm will include LYT-200 plus tislelizumab or gemcitabine/nab-paclitaxel. In part 2, LYT-200 will be combined with either tislelizumab or nab-paclitaxel (Abraxane).

The primary end points in part 1 were the incidence of treatment-emergent adverse effects and incidence of dose-limiting toxicities, while in part 2 it is progression-free survival or objective response rate. Secondary end points for part 1 included a pharmacokinetic profile for the maximum plasma concentration, time to maximum plasma concentration, area under the curve, and pharmacodynamics.

Patients were eligible for enrollment if they were older than 18 years, could comply with the study protocol, and had histologically confirmed unresectable locally advanced or metastatic cancer. In part 1, the head and neck cancer cohorts 11 and 12 patients must have histologically confirmed locally advanced or metastatic squamous cell carcinoma of the head and neck including cancers of the oral cavity, oropharynx, hypopharynx, or larynx.

Additionally, patients must have a life expectancy of over 3 months, an ECOG performance status of 0 or 1, and can undergo pre- and posttreatment biopsies. Those with measurable disease, adequate hematologic and end-organ function, and no evidence of serious infection were also included.

Patients were excluded if they were diagnosed with metastatic cancer of an unknown primary, had a current illicit drug addiction, or had clinically significant, active uncontrolled bleeding. If patients had received other investigational agents or were part of another clinical trial within 3 weeks of study treatment, had radiation therapy within 4 weeks of the first study dose, and had fungating tumor masses they were also excluded.

"By granting fast track designation to LYT-200 for head and neck cancers, the FDA continues to highlight areas of critical need within oncology as well as the potential for LYT-200," said Aleksandra Filipovic, MD, PhD, head of oncology at PureTech. "As galectin-9’s role in suppressing immune-mediated activity has been well-validated, it represents an important area of clinical research, especially in aggressive cancers with increased mortality."

References

1. PureTech receives FDA fast track designation for LYT-200 in head and neck cancers. News release. PureTech. April 11, 2024. Accessed April 12, 2024. https://shorturl.at/uwZ48
2. LYT-200 alone and in combination with chemotherapy or tislelizumab in patients with locally advanced or metastatic solid tumors. ClinicalTrials.gov. Accessed April 12, 2024. https://shorturl.at/ceDFG