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 

The ImmunoCobiVem trial enrolled 185 patients with untreated, 

 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 

 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 

 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.

Videos

Thach-Giao Truong, MD, discusses the ImmunoCobiVem trial of early switch from targeted therapy to immunotherapy in advanced BRAF V600–positive melanoma.

Dr Truong on Targeted Therapy vs Immunotherapy in BRAF V600–Positive Melanoma

Thach-Giao Truong, MD, medical director, Melanoma Program, Cleveland Clinic, discusses long-term findings from the phase 2 ImmunoCobiVem trial (NCT02902029) investigating early switch from targeted therapy to immunotherapy in patients with advanced 

ImmunoCobiVem enrolled 185 patients with previously untreated, 

 V600–mutated unresectable or metastatic melanoma. All patients received the targeted therapy combination vemurafenib (Zelboraf) plus cobimetinib (Cotellic) during a 3-month run-in phase. During the randomization phase, patients were randomly assigned 1:1 to arm A (n = 69), in which they continued to receive vemurafenib plus cobimetinib, or arm B (n = 66), in which they switched to receive the immunotherapy agent atezolizumab (Tecentriq). The primary end point was PFS from the start of the run-in phase until first disease progression (PFS1). The time from first disease progression to second disease progression served as a secondary end point.

Patients in arm A, who switched from the targeted therapy combination to single-agent immunotherapy, had worse PFS1 outcomes vs those in arm B who did not switch therapies and instead continued to receive targeted therapy, Truong begins. This included loss of response after the switch, Truong adds. The median PFS1 was 13.0 months (95% CI, 9.9-15.6) in arm A vs 5.9 months (95% CI, 5.5-8.3) in arm B (HR, 0.61; 95% CI, 0.41-0.91; stratified 

 = .006). These data indicate that single-agent immunotherapy is not as effective as a targeted therapy combination in the treatment of patients with advanced 

These findings also further contextualize other datasets in the melanoma field, such as the phase 3 DREAMseq trial (NCT02224781), which investigated dabrafenib (Tafinlar) plus trametinib (Mekinist) followed by nivolumab (Opdivo) plus ipilimumab (Yervoy) vs the reverse sequence in patients with advanced 

-mutant melanoma, Truong explains. Other melanoma clinical trials have raised questions about the efficacy of frontline immunotherapy-containing triplet vs doublet regimens, she emphasizes. Overall, research with immunotherapy in melanoma indicates that the efficacy of this treatment class depends on the line of therapy it is administered in, as well as the specific regimen used, Truong concludes.

Thach-Giao Truong, MD, discusses the ImmunoCobiVem trial investigating the switch from targeted therapy to immunotherapy in advanced BRAF V600+ melanoma.

Paolo Tarantino, MD is an Advanced Research Fellow in the Breast Oncology Program at Dana-Farber Cancer Institute and Harvard Medical School.

Professor of Medicine in the Division of Medical Oncology

, where he is Co-Leader for the Precision Cancer Department at Duke University's School of Medicine. 

Welcome to OncLive On Air®! I’m your host today, Jax DiEugenio.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we invited experts from across oncology specialties to discuss the abstracts and presentations they are most looking forward to seeing at the 2024 ESMO Congress.

Emre Yekedüz, MD, an associate professor of medical oncology at Ankara University in Turkey and a research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts, shared insights on his latest work in genitourinary malignancies, particularly muscle-invasive bladder cancer. 

Thach-Giao Truong, MD, a hematologist and medical oncologist at the Cleveland Clinic in Ohio who specializes in skin cancers including basal cell carcinoma, melanoma, and Merkel cell carcinoma, highlighted her recent findings in targeted therapies for advanced skin cancers.

John H. Strickler, MD, an associate professor of medicine in the Division of Medical Oncology at Duke University in Durham, North Carolina, emphasized key updates in the treatment of gastroesophageal malignancies, where he sees significant progress on the horizon.

David Spigel, MD, chief scientific officer and medical oncologist at Sarah Cannon Research Institute in Nashville, Tennessee, discussed the expanding lung cancer clinical trial program he oversees, ensuring patients have access to cutting-edge therapies.

Finally, Paolo Tarantino, MD, a researcher at the European Institute of Oncology and clinical research fellow at Dana-Farber Cancer Institute, focused on advancements in breast cancer research, particularly in HER2-targeted therapies and antibody-drug conjugates.

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Podcasts

Experts from across oncology specialties discuss the abstracts and presentations they are most looking forward to seeing at the 2024 ESMO Congress.

Thach-Giao Truong, MD

Articles

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

Dr Truong on Targeted Therapy vs Immunotherapy in BRAF V600–Positive Melanoma

Oncology Experts Preview Top Abstracts From the 2024 ESMO Congress