The Evolving NSCLC Treatment Paradigm: Where Will Your Asset Fit?
New therapeutics targeting actionable biomarkers or other aberrations of malignancy, are evolving treatment paradigms at an accelerated pace, and challenge drug developers to pressure test clinical development strategies.
In particular, the NSCLC treatment landscape has seen therapeutic advances define new patient segments and new clinical benefit thresholds that drugs in development will have to meet to be therapeutically relevant.
- The Phase III ADAURA study. It investigated adding osimertinib to adjuvant therapy for patients with completely resected Stage IB-IIIA disease harboring an EGFR mutation. For Stage II-IIB disease, 2-year DFS was improved to 90% from 44% with placebo, a HR of 0.17. Including patients with stage IB disease, the 2-year disease-free survival rates were 89% vs 53%, respectively. This will be practice changing. However, because osimertinib is already approved for metastatic NSCLC harboring certain EGFR mutations, some physicians continue to believe that it should remain a 1L SoC until more mature adjuvant results are reported.
- Second, the Phase II VISION study reported that Tepotinib, a highly selective oral MET inhibitor, induced an ORR of 46.5%, a median duration of response of 11.1 months, and a DCR of 65.7% in patients with locally advanced or metastatic disease that harbored a MET exon 14 skipping mutation. Although these MET exon 14 skipping mutations occur in 3%-4% of NSCLC, in September 2019, the FDA granted Tepotinib a Breakthrough Designation in NSCLC patients with this MET aberration who had failed prior platinum containing therapy. Is this a future SoC?
- And third, the Phase II CITYSCAPE trial investigated adding the anti-TIGIT mAb tiragolumab, versus placebo, to atezolizumab, in chemotherapy-naïve locally advanced or metastatic NSCLC patients with a PD-L1 tumor proportion score of at least 1%. ORR of 37.3% vs 20.6% in favor of the tiragolumab study arm were reported at ASCO, as were mPFS rates of 5.6 months vs 3.9 months, respectively. The ASCO presentation also reported an even more favorable outcomes in an exploratory subgroup, patients with TPS scores > 50%. Is this another IO-IO combination regimen that will join the Nivolumab-Ipilimimab doublet so as to again redefine 1L options?
So, in the context of these, and other promising trial results, the challenge before you is how will you design a drug development strategy that will deliver your asset as a differentiated and therapeutically relevant treatment option to the practicing oncologist.
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