First Patient Dosed With KSQ-004EX In Solid Tumor Clinical Trial

KSQ-004EX is being evaluated in solid tumors including melanoma, non-small cell lung, head and neck, colorectal, pancreatic and cervical cancer.

The first patient has been dosed in a phase 1/2 clinical trial evaluating KSQ-004EX in solid tumors including melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC), pancreatic cancer and cervical cancer.

The development was announced in a news release issued by clinical-stage biotechnology company KSQ Therapeutics, Inc.

The trial, according to the news release, is an open-label dose escalation study for patients with advanced solid tumors, with the primary objective of the phase 1 portion of the trial being to evaluate the safety and tolerability of the drug, and the primary objective of the phase 2 portion being to study the antitumor activity in indication-specific cohorts of patients.

KSQ-004EX, as explained by the National Cancer Institute on its website, is made in a laboratory from tumor-infiltrating lymphocytes, or TILs, a type of white blood cell from the patient’s tumor tissue, and may kill tumor cells by blocking genes that help the tumor form and grow.

The first patient treated with KSQ-004EX was enrolled by Dr. Rodabe Amaria, a professor of melanoma medical oncology and principal investigator of the study at The University of Texas MD Anderson Cancer Center in Houston, according to the news release.

KSQ-004EX is described as a dual SOCS1 and Regnase-1 edited CRISPR/Cas9 engineered tumor Infiltrating lymphocyte (eTIL) therapy, designed to inactivate both the SOCS1 and Regnase-1 genes.

“The promise of TIL therapy remains high, but current approaches fall short of addressing the needs of most patients with solid tumors. Preclinically, the combined inactivation of SOCS1 and Regnase-1 in KSQ-004EX strongly increased anti-tumor functionality. We believe these enhancements give KSQ-004EX the potential to significantly advance TIL therapy for the treatment of solid tumors,” said Qasim Rizvi, CEO of KSQ and CEO-Partner at Flagship Pioneering, in the news release.

More about TIL therapy

CURE previously spoke with Dr. Goran Micevic, assistant professor of dermatology and dermatopathology at Yale and member of the Yale Cancer Center, to discuss TIL therapy and how the science behind it.

“The basic idea is that you take T cells, which are immune cells that can recognize foreign threats from the patient, you expand them outside of the patient's body and then you reinfuse them in an effort to battle cancer,” Micevic explained. “And so this is kind of a live therapy, as opposed to chemotherapies, which are chemicals and molecules, and as opposed to immune therapies, which we've kind of [been] witnessing the revolution [of], which are still molecules. So these are live cells, and they're the patient's own cells.”

TIL therapy, Micevic noted, is a fairly complex therapy that has gone through a number of iterations, and has to date only been available in an inpatient setting.

“The reason for that is that when you infuse somebody with their own T cells, there's a lot of preparatory work that you need to do,” he said. “So it's not unlike a bone marrow transplant. It's very involved really. So you have to prepare the patient and essentially immunosuppress them."

“So, you give them a lymphoablative therapy over a period of about a week prior to them receiving their own cells, and then when they receive the cells, you still have to receive what we call interleukin-2, high-dose interleukin-2, which is a chemical that actually activates T cells to kind of wake them up from their slumber. But that treatment also induces some unpleasant symptoms which are not unlike an inflammatory condition called sepsis.”

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