FDA Grants Orphan Drug Status to LYT-200 for Pancreatic Cancer

The FDA has granted orphan drug designation to LYT-200 for the treatment of patients with pancreatic cancer, according to a press release issued by PureTech Heal plc.

LYT-200 fully human IgG4 monoclonal antibody, which targeted the protein galectin-9 to treat solid tumors like pancreatic cancer, colorectal cancer, and cholangiocarcinoma. According to preclinical investigations of LYT-200, the agent has high expression of galectin-9 in breast cancer, pancreatic cancer, and cholangiocarcinoma. The drug was associated with a decreased time to disease relapse and poor survival, signaling that galectin-9 may be an important therapeutic target and cancer biomarker.

"The FDA's decision to grant orphan drug designation for LYT-200 reflects its potential as a novel anti-cancer therapy designed to block multiple immunosuppressive pathways in the tumor microenvironment," said Julie Krop, MD, chief medical officer at PureTech, in a press release. "Too many pancreatic cancer patients do not respond to existing immunotherapy agents and other standard of care regimens. We are looking forward to advancing LYT-200 through the clinic in hopes of meeting this substantial need."

A phase 1/2 adaptive design trial (NCT04666688) is currently underway to assess safety, pharmacokinetics (PK), and anti-tumor activity of LYT-200 both alone and in combination with chemotherapy as treatment of patients with metastatic solid tumors.

The study is open-label, uncontrolled, and being conducted across multiple centers. Initially, a part 1 dose-finding analysis will be conducted using a continuous reassessment method. This initial part of the study will determine the dose-limiting toxicities (DLTs) of LYT-200 as well as the recommended phase 2 dose of the drug. In part 2, the cohort will be expanded to specific solid tumors like pancreatic cancer, cholangiocarcinoma, and others following a Simon’s 2-stage optimal design.

The coprimary end points of part 1 are the incidence of treatment-emergent adverse events and the incidence of DLTs. The coprimary end points of part 2 include progression-free survival and objective response rate. The secondary end points, which will be explored during both parts of the study include PK, and pharmacodynamics.

To be eligible for inclusion in the study, patients must be aged 18 years of age or older with histologically confirmed unresectable metastatic cancer. Both males and females are permitted in the study, but female patients must not be pregnant. All patients are required to have a life expectancy of greater than 3 months, an ECOG performance status of 0 to 1, be negative for coronavirus SARS-CoV-2, have measurable disease per RECIST v1.1, have adequate hematologic and organ function, and show no evidence of active infection, serious infection within 4 weeks, or infection requiring antibiotics.

The study excludes individuals who have been previously treated with investigational agents for the treatment of a solid tumor within 4 weeks of study entry, as well as those who received radiation therapy within 4 weeks of study entry. In addition, patients with fungating tumors masses, locally advanced pancreatic ductal adenocarcinoma without distant organ metastatic deposits, as well as patients with history of second malignancy and previous toxicities that may interfere with study treatment are not permitted to receive LYT-200 in the phase 1/2 study.

Patients with metastatic solid tumors in Arizona, Colorado, Florida, Michigan, Minnesota, Tennessee, and Texas are being actively recruited to enroll in the study.

_References:

_{1. PureTech Receives orphan drug designation for wholly owned candidate lyt-200 for the treatment of pancreatic cancer. News release. November 15, 2021. Accessed November 15, 2021. https://bit.ly/3nfRvmg}

_{2. LYT-200 alone and in combination with chemotherapy or anti-pd-1 in patients with metastatic solid tumors. Clinicaltrials.gov. Accessed November 15, 2021. https://bit.ly/3wNEWlc}