A breakthrough that is very personal – CheckMate 76K

There is a strong back-story to the popular joint win in this year’s Australian of the Year award.

Professor Georgina Long and Professor Richard Scolyer’s enduring partnership has saved thousands of lives from melanoma, known as Australia’s national cancer. But is also very personal for them. 

Professor Scolyer is currently being treated for incurable grade 4 brain cancer, using experimental immunotherapy based on the pair’s melanoma breakthroughs. 

Less than a decade ago, advanced melanoma was fatal – but thanks to their immunotherapy approach, which activates a patient’s own immune system, it has become a curable disease.   

With over 1,000 published articles referenced to each, their groundbreaking and ongoing phase 3, double-blind CheckMate 76K trial, has been transformative in terms of displaying their work’s potential – specifically using the drug nivolumab. 

In the study’s latest update, published October last year, Professor Long highlighted that although stage II melanoma was less advanced than stage III or stage IV disease, stage II disease was associated with a greater absolute number of eventual deaths due to its far greater incidence. 

“Real-world studies evaluating patients before the approval of adjuvant checkpoint inhibitors suggest that the 5-year risk of recurrence in patients with stage IIB or stage IIC disease is approximately 35% and 50%, respectively, with 5-year melanoma-specific survival (MSS) rates of 83–87% for IIB and 70–82% for IIC,” she said.  

“MSS rates in patients with stage IIB/IIC disease are like those for stage IIIA (93%), stage IIIB (83%) and stage IIIC (69%) disease. Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease.” 

From 28 October 2019 through 3 November 2021, 986 patients in 20 countries worldwide were screened at 129 sites, and 790 were randomized 2:1 to receive nivolumab (526 patients, stratified by tumour category to 480mg) or placebo (264 patients) at 119 sites, every 4 weeks for 12 months. 

“Of the patients treated with nivolumab, 49.0% completed blinded phase treatment and 12.2% were still on treatment; for placebo, this was 59.8% and 14.8%, respectively,” Professor Long said. 

“The primary endpoint was investigator-assessed recurrence-free survival (RFS), while secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus the placebo (hazard ratio (HR = 0.42;), with a 12-month RFS of 89.0% versus 79.4%. 

“The improvement in RFS with nivolumab versus placebo was presumably driven by numerically fewer distant recurrences (4.9% versus 11.7%) and regional recurrences, but was consistent across stages, with an HR of 0.34 for patients with stage IIB disease and 0.51 for patients with stage IIC disease. 

“Improvement was also observed with adjuvant nivolumab for the key secondary endpoint of DMFS, with 8.0% of patients in the nivolumab group and 15.5% of patients in the placebo group experiencing distant recurrence or death (HR = 0.47).” 

Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients, and one treatment-related death (0.2%) occurred with nivolumab. 

Overall, the study found that Nivolumab was an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma, and data from the trial has also led to the FDA and European Medicines Agency’s approval of the adjuvant pembrolizumab, in patients with resected stage IIB/C melanoma. 

The full study can be accessed here: https://www.nature.com/articles/s41591-023-02583-2