FDA Fast Tracks Early Stage Novel Tumor-Infiltrating Lymphocyte Therapy

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The FDA has granted Fast Track designation to Biosyngen’s BST02, a novel T-cell therapy for all types of liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma.¹ The FDA approved an Investigational New Drug Application for BST02 to advance to clinical trials in October 2023, and the therapy was approved by China’s National Drug Administration earlier this month.²

BST02 is a tumor-infiltrating lymphocyte (TIL) therapy, which is a cell-based immunotherapy that harnesses a patient’s immune cells from the microenvironment of the solid tumor to eliminate tumor cells.³

“TIL therapy has some unique advantages in the treatment of solid tumors, but it still faces a series of challenges,” wrote the authors of a study published by Cancers. “The tumor immunosuppressive microenvironment is still the main obstacle of TIL therapy. Furthermore, there is still considerable room for improvement in the isolation and expansion of effective tumor-reactive T cells, and alternative combined therapies still need to be explored.”³

BST02 is the first TIL therapy to have advanced to the clinical stage that was developed to treat all types of liver cancer.² BST02 does not require high doses of interleukin-2 and the drug is cryopreserved, which allows it to overcome distance issues associated with traditional TIL therapies, according to Biosyngen.²

An open-label, single-arm, investigator-initiated Phase I trial (NCT06173726) is currently evaluating the treatment.⁴ Enrollment criteria include being between 18 and 75 years of age with histologically or cytologically confirmed locally advanced or metastatic liver cancer, including HCC, intrahepatic bile duct carcinoma, and metastatic liver cancer; for those with HCC and cholangiocarcinoma, the disease must be stage B or C and not amenable to local treatment; and patients with metastatic liver cancer cannot be eligible for radical surgery.

Further, those with locally advanced liver cancer must have received a minimum of frontline systemic therapy and be found unsuitable for, or have declined, systemic therapy following failure of prior treatment. Those with metastatic disease must have experienced disease progression or intolerance to second-line or later therapy, have declined standard therapy, or have been given an inappropriate therapy recommendation per the investigator.

Patients must be fit enough to undergo at least one operation without radiation or local treatment within 28 days to extract tumor lesions that have an estimated lesion volume of at least 8 cm³— not including necrotic areas—to prepare BST02 cells.

Other criteria for enrollment include having at least one measurable lesion per RECIST v1.1 criteria; ECOG performance status of 0 or 1; a Child-Pugh cirrhosis score of seven or fewer points; a minimum of three months of expected survival time; and adequate organ and bone marrow function within the screening period or 14 days before TIL sampling. Further, adverse events (AEs) experienced with prior treatment that were not found by investigators to pose a safety risk must be resolved to grade 1 or lower before tumor sampling per the Common Adverse Event Evaluation Criteria.

Investigators will administer 250 mg or 1.5 g/m² of a single intravenous infusion of cyclophosphamide three days prior to administration of BST02 to stimulate lymphocyte proliferation. The study’s primary endpoints are AE occurrence and incidence, reports of severe AEs, and dose-limiting toxicity. The study has primary completion date of December 5, 2026.

References

1. Biosyngen announces FDA fast track designation for BST02 in treatment of liver cancer. News release. Biosyngen. February 1, 2024. Accessed February 2, 2024. https://www.prnewswire.com/news-releases/biosyngen-announces-fda-fast-track-designation-for-bst02-in-treatment-of-liver-cancer-302050377.html

2. Biosyngen’s BST02, the world’s first TIL therapy for liver cancer, is granted an IND approval by FDA. News release. Biosyngen. October 26, 2023. Accessed February 2, 2024. https://www.prnewswire.com/news-releases/biosyngens-bst02-the-worlds-first-til-therapy-for-liver-cancer-is-granted-an-ind-approval-by-fda-301968656.html

3. Zhao Y, et al. Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges. Cancers (Basel). 2022 Aug 27;14(17):4160. doi: 10.3390/cancers14174160. PMID: 36077696; PMCID: PMC9455018. Accessed February 2, 2024.

4. Investigator-initiated phase I exploratory clinical study of the safety, tolerability, and efficacy of BST-2 injection in the treatment of locally advanced/metastatic liver cancer. ClinicalTrials.gov. Updated December 18, 2023. Accessed February 2, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06173726