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Novartis reports late-breaking data from phase III COMBI-i trial of spartalizumab (PDR 001) with Tafinlar and Mekinist in advanced melanoma.
Novartis announced detailed results from the Phase III COMBI-i trial evaluating the investigational immunotherapy spartalizumab (PDR 001) in combination with the targeted therapies Tafinlar (dabrafenib) and Mekinist (trametinib) compared to Tafinlar + Mekinist alone.
The efficacy data achieved in the trial’s control arm among patients treated with Tafinlar + Mekinist represent the longest progression-free survival results (PFS) observed across multiple Phase III studies. The trial did not meet its primary endpoint of investigator-assessed progression-free survival (PFS) for patients treated with the investigational triplet therapy. The COMBI-i study was conducted among treatment-naive patients with advanced BRAF V600 mutation-positive cutaneous melanoma. Results were presented as a late-breaking oral presentation during the European Society of Medical Oncology (ESMO) Virtual Congress 2020 .
"For treating physicians and patients alike, the durable, progression-free survival seen with dabrafenib + trametinib in COMBI-i confirms that this targeted therapy combination remains a gold standard treatment for people with advanced BRAF-mutated melanoma,” said Dr. Paul Nathan, consultant medical oncologist, Mount Vernon Cancer Centre, United Kingdom, and COMBI-i principal investigator. “The good news is that the control arm of the study performed better than we originally expected, with the efficacy of dabrafenib + trametinib improving consistently over time. Although the study did not meet its primary endpoint, an important trend was seen in favor of the triple therapy arm. There is clearly more for us to learn about patients who may benefit from the potential addition of an immunotherapy.”
Findings from this randomized, double-blind, placebo-controlled study showed a median time of PFS of 16.2 months for patients treated with the triple therapy (n=267) compared to 12.0 months for patients receiving the combination Tafinlar + Mekinist alone (n=265; hazard ratio [HR] 0.82; 95% CI 0.655-1.027; p=0.042). Overall response rate was 68.5% for spartalizumab with Tafinlar + Mekinist (95% CI, 62.6-74.1%) compared to 64.2% for Tafinlar + Mekinist alone (95% CI, 58.1-69.9%). A significant duration of response (DOR) was seen in the study as median DOR for the triple therapy was not reached at two-year data cutoff, compared to 20.7 months with Tafinlar + Mekinist.
“The study results reinforce that patients taking Tafinlar + Mekinist continue to see durable responses and a meaningful progression-free survival benefit, consistent with data reported in previous Phase III studies.”
About the COMBI-i Study : COMBI-i was a Phase III, double-blinded global study (NCT02967692) evaluating the investigational anti-PD1 therapy spartalizumab in combination with Tafinlar + Mekinist compared to Tafinlar + Mekinist and placebo as first-line therapy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The study was conducted in three parts. In the safety run-in (part 1), the primary endpoint was incidence of dose-limiting toxicities, and in the biomarker cohort (part 2), the primary endpoint was immune microenvironment and biomarker modulation. In the randomized portion of the study (part 3), the primary endpoint was investigator-assessed progression-free survival. COMBI-i study participants were classified as having either Stage IIIC (unresectable) or Stage IV (metastatic) disease and received study treatments as first-line therapy. No new side effects were seen and the safety profile in the control arm was consistent with what has been observed in previous studies. COMBI-i also evaluated a new side effect management protocol to address pyrexia – or fever – a common side effect seen among targeted therapies.
Serious treatment-related adverse events (TRAEs) grade greater than 3 occurred in 23.2% of patients in the triple therapy arm compared to 11% in the Tafinlar + Mekinist arm. The most common grade greater than 3 adverse events independent of treatment relationship observed in the triple therapy and Tafinlar + Mekinist arms were blood creatine phosphokinase increase (7.9% vs 7.2%), pyrexia (5.2% vs 3.0%), aspartate aminotransferase increase (3.7% vs 1.1%), fatigue (3.4% vs 1.9%), rash (3.4% vs 0.4%), asthenia (2.2% vs. 1.1%), headache (1.1% vs. 1.5%), diarrhea (0.7% vs. 1.9%), nausea (0.7% vs 0.4), arthralgia (0.7% vs 1.5%), and chills (zero vs. 0.8%). TRAEs leading to discontinuation of all 3 study drugs occurred in 12% compared to 8% of patients, respectively.
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Condition: Metastatic Melanoma
Type: drug