An international, randomized, open-label phase III study comparing the efficacy and safety of nivolumab plus bempegaldesleukin—an experimental interleukin (IL)-2–based drug—vs nivolumab monotherapy in patients with previously untreated, unresectable, or metastatic melanoma is now enrolling participants. The study design (abstract TPS9601) was presented during a poster session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago.
“The prognosis today is much better than it was 10 or 15 years ago, but that still means that half of the patients that come with metastatic disease will end up dying of their disease. So, there’s still a huge amount of work to be done,” said Mario Sznol, MD, of Yale Cancer Center in New Haven, Connecticut, an author on the poster, in an interview with Cancer Network.
Though high-dose IL-2 monotherapy is effective and can even be curative in patients with metastatic melanoma, its use has largely been replaced by newer, more effective, immunotherapy treatments due to its poor toxicity profile and need for inpatient hospital administration, explained Sznol.
“The hypothesis is that now if you combine this pegylated form of IL-2, which you can give subcutaneously once a week instead of having to bring the patients into the hospital, that the IL-2 interacts with … nivolumab, to improve its activity,” said Sznol.
The phase II PIVOT-02 trial is currently evaluating the safety and efficacy of the nivolumab-bempegaldesleukin combination in solid tumors, such as melanoma, renal cell carcinoma, and urothelial carcinoma. The combination appears to be clinically active and well tolerated.
“It’s a very important concept to test. There are many other ways of adding to nivolumab, many other kinds of drugs, that will be tested or that are being tested in phase III trials,” said Sznol, “and we’ll probably accelerate this study in the near future.”
For the phase III study, the investigators are seeking approximately 764 patients. Eligible patients must be at least 12 years of age, with histologically confirmed stage III (unresectable) or stage IV melanoma and an ECOG performance score of at least 1 or a Lansky play-performance score of at least 80% (for those 12–17 years of age). Key exclusion criteria include active brain or leptomeningeal metastases, uveal melanoma, active (known or suspected) autoimmune disease, and/or a recurrence within 6 months of completing an adjuvant treatment.
Patients will be randomized to receive bempegaldesleukin (0.006 mg/kg IV every 3 weeks) plus nivolumab (360 mg IV every 3 weeks) or nivolumab alone (360 mg IV every 3 weeks) for up to 24 months, until progression or unacceptable toxicity. Stratification factors include PD-L1 status, BRAF mutation status, and lactate dehydrogenase level. The primary endpoints are objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival. The secondary endpoints include safety, ORR and PFS by investigator review, and ORR and PFS by central review and OS in a population of patients with biomarker data available at baseline.