HSPPC-96 + temozolomide

HSPPC-96 + temozolomide is a combination therapy used primarily for treating glioblastoma multiforme (GBM), a type of brain cancer. This combination consists of an autologous heat shock protein peptide complex-96 (HSPPC-96) vaccine derived from the patient's own tumor tissue, administered alongside temozolomide, which is a standard chemotherapy drug for GBM. ## Description HSPPC-96 (also known as vitespen) is an autologous tumor-derived heat shock protein peptide complex vaccine that is made from each individual patient's tumor tissue. The vaccine is designed to reprogram the patient's immune system to better target tumor cells[5]. It works by stimulating an antitumor immune response, as evidenced by significant increases in tumor-specific immune response after vaccination[2]. Temozolomide is an alkylating agent used as standard chemotherapy for GBM. The combination therapy typically follows the "Stupp's regimen," which includes surgical resection followed by radiotherapy plus concurrent temozolomide chemotherapy[2]. In clinical trials, HSPPC-96 vaccination was administered concurrently with the beginning of adjuvant temozolomide chemotherapy. The vaccine was typically given via subcutaneous injection in 25-μg doses weekly for 6 weeks, with cyclophosphamide (400 mg) administered intravenously before each vaccine injection[2][7]. ## Clinical Evidence Phase 2 trials of HSPPC-96 in combination with temozolomide for newly diagnosed GBM have shown promising results: - A Phase 2 trial with 46 patients across eight US centers showed a median progression-free survival (PFS) of 17.8 months, with 63% of patients progression-free at twelve months and 20% progression-free at 24 months. This represented a considerable improvement compared to the standard of care (radiation plus temozolomide alone), which typically results in a PFS of 6.9 months[3]. - Median overall survival was 23.3 months, with an 85% survival rate at 12 months. This compared favorably to the standard of care, which typically results in a median overall survival of 14.6 months[3]. - The combination therapy was well-tolerated, with no grade 3 or 4 vaccine-related adverse events reported during treatment[2]. ## Development Status As of 2013, Agenus planned to hold an end of Phase 2 meeting with the US Food and Drug Administration to discuss a Phase 3 trial that could potentially lead to marketing approval of the HSPPC-96 vaccine as a treatment for patients with newly diagnosed GBM[3]. More recently, a Phase 2 trial (NCT03018288) has been investigating the combination of radiation therapy plus temozolomide and pembrolizumab with and without HSPPC-96 in newly diagnosed glioblastoma[1][4][8]. The canonical name for this drug combination is HSPPC-96 + temozolomide, with HSPPC-96 also known as vitespen. This combination represents an innovative approach to GBM treatment that leverages both standard chemotherapy and personalized immunotherapy.