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.
§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).