IMspire150: The First Pivotal Study Combining Immunotherapy With BRAF/MEK-Targeted Therapy ^1,3

A Phase III, double-blind, randomized, placebo-controlled, multicenter study that evaluated TECENTRIQ, in combination with COTELLIC^® (cobimetinib) and ZELBORAF^® (vemurafenib), in patients with 1L BRAF V600+ unresectable or metastatic melanoma

During the 28-day targeted therapy run-in cycle, patients received COTELLIC 60 mg qd and ZELBORAF 960 mg bid on Days 1 to 21; on Days 22 to 28, patients in the treatment arm received ZELBORAF 720 mg + placebo* bid, and patients in the control arm received ZELBORAF 960 mg bid. During Cycle 2 and onward, patients in the treatment arm received TECENTRIQ 840 mg intravenously (IV) on Days 1 and 15, in combination with COTELLIC 60 mg qd on Days 1 to 21 and ZELBORAF 720 mg + placebo* bid on Days 1 to 28; in the control arm, patients received placebo IV on Days 1 and 15, in combination with COTELLIC 60 mg qd on Days 1 to 21 and ZELBORAF 960 mg bid on Days 1 to 28. In both arms, patients were treated until disease progression or unacceptable toxicity. Randomization was stratified by geographic location and baseline LDH. This study excluded patients if they had a history of autoimmune disease; administration of a live, attenuated vaccine within 28 days prior to randomization; administration of systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomization; and/or active or untreated CNS metastases.

Primary endpoint ¹

• Progression-free survival^†

Key secondary endpoints ¹

• Overall response rate^†‡
• Duration of response^†‡
• Overall survival^§

1L=first line; bid=twice a day; ECOG=Eastern Cooperative Oncology Group; PS=performance status; qd=every day; RECIST=Response Evaluation Criteria In Solid Tumors.
*Patients received an oral placebo so that the same number of pills was received in both treatment arms.
^†As assessed by the investigator, per RECIST v1.1.
^‡Confirmed responses.
^§At the time of the analysis, median OS was evaluated as part of a prespecified analysis and the data were not mature.

Baseline characteristics were well balanced between treatment arms ³

IC=tumor-infiltrating immune cell; PD-L1=programmed death-ligand 1.
^||All patients are reported as BRAF V600 mutation-positive status in melanoma tumor tissue by a locally approved test. BRAF mutation genotype is reported missing when sample was not centrally analyzed owing to insufficient tumor sample.
^¶PD-L1 positivity was based on the proportion of cells per tumor area occupied by PD-L1–expressing IC of any intensity (% IC). For percentage of IC, immunohistochemistry staining was scored as 0 (<1%), 1 (≥1% to <5%), 2 (≥5% to <10%), or 3 (if ≥10% of cells per area were PD-L1 positive).