Regorafenib, nivolumab, chemo combo found safe and effective for various cancers, heading to phase 3 trial

Researchers at Memorial Sloan Kettering Cancer Center in New York have completed a phase II trial of chemotherapy combining the drugs nivolumab and regorafenib.

The results of the study, “First-Line Regorafenib with Nivolumab and Chemotherapy in Advanced Esophageal, Gastric, or Gastroesophageal Junction Cancer in the United States: A Single-Arm, Single-Center, Phase 2 Study,” Lancet Oncology, suggest that regorafenib and nivolumab with chemotherapy are safe and show some antitumor activity in patients with advanced esophagogastric cancer. Based on these results, a randomized Phase 3 clinical trial of this combination is planned.

Previous studies have shown potential efficacy of each drug against esophagogastric adenocarcinoma. Regorafenib has shown promise in improving outcomes in refractory esophagogastric cancer, nivolumab (an anti-PD-1 antibody) has been shown to be beneficial in combination with chemotherapy, and chemotherapy itself is the standard It is a treatment option. It was hoped that the combination of these agents might improve the overall efficacy of treatment and lead to better outcomes.

Despite the initial benefits of immunotherapy (such as nivolumab) and chemotherapy in treating esophagogastric cancer, many patients eventually develop treatment resistance. The addition of regorafenib, which can modulate the tumor microenvironment and enhance immune responses, was a strategic approach that could overcome or delay the development of resistance.

Nivolumab is an immune checkpoint inhibitor that can activate the patient’s own immune system to target cancer cells. In addition to its direct anti-tumor effects, regorafenib can enhance the function of natural killer cells and CD8.⁺ T cells inhibit immunosuppressive factors produced by tumors.

Esophagogastric cancer is the second leading cause of cancer-related deaths, causing approximately 1.3 million deaths annually. Many patients are diagnosed with metastatic disease, which is difficult to treat effectively because it spreads to different areas of the body.

The trial was conducted at Memorial Sloan Kettering Cancer Center and had a final sample size of 35. Participants received combination therapy including FOLFOX chemotherapy, nivolumab, and oral regorafenib. The primary endpoint was 6-month progression-free survival, and safety was assessed in all patients who received at least one dose of any study treatment.

At 6-month assessment, 25 of 35 evaluable patients (71%) were progression-free, an improvement of 18% compared with the primary endpoint of 53% in historical controls achieved.

A follow-up evaluation performed approximately 18 months later revealed that fatigue was the most common adverse event (92% of patients). Serious adverse events occurred in 26% of patients and included acute kidney injury (8%), hepatotoxicity (5%), sepsis (5%), dry skin, pruritus or rash (3%), nausea ( 3%), gastric perforation (3%). There were no treatment-related deaths.