Dr Truong on the Background of the ImmunoCobiVem Trial in BRAF V600+ Melanoma

Thach-Giao Truong, MD, medical director, Melanoma Program, Cleveland Clinic, discusses the background of the phase 2 ImmunoCobiVem trial (NCT02902029), which evaluated early switch from targeted therapy to immunotherapy in patients with advanced BRAF V600–positive melanoma.

The ImmunoCobiVem trial enrolled 185 patients with untreated, BRAF V600–mutated unresectable or metastatic melanoma. All participants began with a 3-month run-in phase of the targeted therapy combination vemurafenib (Zelboraf) and cobimetinib (Cotellic). Following this, patients were randomly assigned 1:1 into 2 groups: Arm A (n = 69), in which patients continued to receive vemurafenib plus cobimetinib, and Arm B (n = 66), in which patients switched to receive the immunotherapy agent atezolizumab (Tecentriq). The primary end point was progression-free survival (PFS1), measured from the start of the run-in phase to the first disease progression. A secondary end point assessed the time from first to second disease progression.

This trial offered an interesting approach to evaluating the optimal sequencing of targeted therapy and immunotherapy in BRAF V600–mutated metastatic melanoma, Truong begins. Unlike other studies, this trial explored a structured switch between targeted therapy and immunotherapy, examining outcomes with a single-agent immunotherapy approach rather than a combination regimen, she states. In one arm, patients started treatment with targeted therapy in a lead-in phase and continued with it, whereas in the other arm, patients also started treatment with targeted therapy but were then transitioned to treatment with single-agent immunotherapy—a less common choice for melanoma monotherapy, Truong reports. This design reflects a novel treatment approach, as prior trials often did not investigate combined immunotherapy for melanoma treatment.

This trial addressed the need for targeted therapy in patients requiring immediate disease control due to rapid progression, often seen in metastatic melanoma with BRAF mutations, she continues. By starting all patients with a lead-in targeted therapy phase, the trial provided insights distinct from other melanoma trials, according to Truong. This strategy avoids the initial drop-off effect often observed when immunotherapy is started without prior disease control in high-risk patients, Truong reports. Consequently, this trial’s unique design acknowledges the critical role of targeted therapy for stabilization before immunotherapy and provides comparative data on maintaining targeted therapy vs transitioning to immunotherapy with a single agent, she concludes.