Breakthrough Clinical Results

MiNK Therapeutics announced the publication of a case report in *Oncogene* showing complete and durable remission in a patient with metastatic, treatment-refractory testicular cancer following treatment with agenT-797, their allogeneic iNKT cell therapy. The patient had progressed after multiple lines of therapy, including platinum-based chemotherapy, autologous stem cell transplant, and multiple immune checkpoint inhibitors. Following a single infusion of agenT-797 alongside nivolumab, the patient achieved complete remission with no evidence of disease over two years. This adds to growing evidence supporting agenT-797's potential in solid tumors, with data from a Phase 2 trial in gastric cancer also showing immune activation and tumor control. The ongoing Phase 2 trial in gastric cancer is actively enrolling.

Emerging Mechanism of Action

Testicular cancer (TC) is highly curable due to effective cisplatin-based chemotherapy. While surgery (radical inguinal orchiectomy) remains the primary treatment, the focus has shifted towards understanding and managing long-term treatment-related complications and refining post-orchiectomy management strategies.

Key Mechanisms of Action and Treatment Advances:

• Cisplatin-based chemotherapy: Remains the cornerstone of TC treatment, particularly for nonseminomatous germ cell tumors (GCTs). Cisplatin exerts its anticancer activity primarily through the generation of DNA lesions, interacting with purine bases on DNA, activating signal transduction pathways, and ultimately leading to apoptosis (programmed cell death).
• Post-orchiectomy management: This is determined by stage, histology, and risk classification. Options include surveillance, systemic therapy (chemotherapy), and nerve-sparing retroperitoneal lymph node dissection.
• Targeted therapies: Research is ongoing to identify novel vulnerabilities in TC biology that can be targeted therapeutically. This includes exploring the role of specific genes and proteins involved in tumor development and progression.
• Immunotherapy: Immune checkpoint inhibitors, which enhance the body's immune response against cancer cells, are showing promise in some types of cancer and are being investigated in TC.
• Addressing treatment-related complications: Long-term effects of cisplatin-based chemotherapy, such as hearing loss, neurotoxicity, and cardiovascular disease, are being actively studied. Research focuses on developing risk-stratified follow-up guidelines, preventive measures, and interventions to mitigate these late effects.
• Refining risk assessment and stratification: Improved understanding of risk factors, including genetic predisposition and cryptorchidism, is crucial for developing personalized treatment strategies and optimizing surveillance protocols.
• Focus on survivorship: Given the high cure rates, there is increasing emphasis on long-term survivorship care, addressing the physical and psychosocial needs of TC survivors.

Challenges and Future Directions:

• Drug resistance: Resistance to cisplatin remains a challenge. Research is ongoing to develop strategies to overcome resistance mechanisms, including combination therapies and novel platinum-based drugs.
• Minimizing side effects: Reducing the long-term side effects of cisplatin-based chemotherapy is a priority. This includes exploring alternative treatment regimens and developing supportive care strategies.
• Improving outcomes for brain metastases: Prognosis for TC with brain metastases remains poor. Research is needed to develop more effective treatments for this patient population.
• Understanding the increasing incidence: The reasons behind the rising incidence of TC are not fully understood. Further research is needed to identify potential environmental and lifestyle factors contributing to this trend.

Overall, the focus in TC research is on refining existing treatments, developing novel therapeutic strategies, and improving long-term outcomes for survivors.

Drug used in other indications