Alexander N. Shoushtari, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discusses the rationale for the ​phase 3 CheckMate-067 trial in advanced melanoma.

​The ​landmark CheckMate-067 trial ​randomized patients with previously untreated, advanced melanoma 1:1:1 to receive nivolumab (Opdivo) plus ipilimumab (Yervoy) followed by nivolumab, nivolumab plus ipilimumab-matched placebo, or ipilimumab plus nivolumab-matched placebo.

During the time of the study, ipilimumab ​monotherapy was considered the standard of care​, says Shoushtari. ​However, nivolumab and pembrolizumab (Keytruda) ​have since become new standards in the space.

As such, the ​study evaluated whether the addition of ipilimumab to nivolumab was superior to nivolumab alone, Shoushtari concludes.

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Alexander N. Shoushtari, discusses the rationale for the ​phase 3 CheckMate-067 trial in advanced melanoma.








Dr. Shoushtari on the Rationale for the CheckMate-067 Trial in Advanced Melanoma

Alexander N. Shoushtari, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discusses the design of the ​phase 3 CheckMate-067 trial in advanced melanoma. 

​The study randomized ​patients with previously untreated, unresectable, stage III or IV melanoma 1:1:1 to receive 1 mg/kg of nivolumab (Opdivo) plus 3 mg/kg of ipilimumab (Yervoy) for 4 doses​, followed by 3 mg/kg of nivolumab​; 3 mg/kg of nivolumab plus ipilimumab-matched placebo; or 3 mg/kg of ipilimumab for 4 doses plus nivolumab-matched placebo until progression or unacceptable toxicity, says Shoushtari.

Less common subtypes, such as mucosal ​and acral melanoma, were included in the study, ​but the majority of patients had cutaneous melanoma, ​adds Shoushtari. Notably, patients with uveal melanoma ​were excluded. 

Ultimately, the trial was powered to detect a difference in progression-free survival and overall survival between nivolumab and ipilimumab​, as well as ​between the combination of nivolumab and ipilimumab and ipilimumab monotherapy, ​Shoushtari explains.

The difference in efficacy between nivolumab monotherapy and the combination regimen, as well as the long-term outcomes of patients with mucosal melanoma served as exploratory analyses of the study, Shoushtari concludes. 

Alexander N. Shoushtari, MD, discusses the design of the ​phase 3 CheckMate-067 trial in advanced melanoma. 

Dr. Shoushtari on the Design of the CheckMate-067 Trial in Advanced Melanoma  

Alexander N. Shoushtari, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discusses the role of nivolumab (Opdivo) and ipilimumab (Yervoy) in mucosal melanoma. 

​Mucosal melanoma is a distinct subtype of melanoma for which the combination of nivolumab and ipilimumab can be used, explains Shoushtari. However, long-term survival is not commonly seen with nivolumab. 

The rarity of this disease makes it difficult to accumulate sufficient clinical data to establish a definitive standard of care for patients with mucosal melanoma, Shoushtari says.

​However, the clinical activity observed with the combination has led to its use as the preferred frontline therapy for patients who can tolerate the ​potential toxicity​ associated with the regimen, Shoushtari concludes.

Alexander N. Shoushtari, MD, discusses the role of nivolumab and ipilimumab in mucosal melanoma. 

Dr. Shoushtari on the Role of Nivolumab and Ipilimumab in Mucosal Melanoma 

Alexander N. Shoushtari, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discusses the significance of the findings from the first-in-human trial evaluating tebentafusp (IMCgp100), a TCR—CD3 bispecific, in patients with advanced melanoma.

This TCR-CD3 bispecific was specifically engineered to mimic the human leukocyte antigen (HLA) molecule that that is found in everybody. Shoushtari says it is amazing to see tebentafusp working in the first-in-human trial, which has generated a lot of excitement among physicians.

The hope is that this agent will work for patients with uveal melanoma, but Shoushtari adds that the success with this mechanism of action can be broadly applied to other targets or those who don’t have this specific HLA type.

Alexander N. Shoushtari, MD, discusses the significance of the findings from the first-in-human trial evaluating tebentafusp, a TCR–CD3 bispecific, in patients with advanced melanoma.

Alexander N. Shoushtari, MD

Articles

Dr. Shoushtari on the Rationale for the CheckMate-067 Trial in Advanced Melanoma

Dr. Shoushtari on the Design of the CheckMate-067 Trial in Advanced Melanoma

Dr. Shoushtari on the Role of Nivolumab and Ipilimumab in Mucosal Melanoma

Dr. Shoushtari on the Data from the First-in-Human Trial for Tebentafusp in Advanced Melanoma