“Bristol-Myers Squibb Company (NYSE: BMY) today announced initial results from the pivotal Phase 3 study, CheckMate -227, evaluating the Opdivo (nivolumab) 3 mg/kg pluslow-dose Yervoy (ipilimumab, 1 mg/kg) combination in first-line advanced non-small cell lung cancer (NSCLC) patients with high tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb). In the study, the combination demonstrated a superior benefit for the co-primary endpoint of progression-free survival (PFS) versus chemotherapy (HR 0.58; 97.5% CI: 0.41 to 0.81; p=0.0002). The PFS benefit was observed regardless of PD-L1 expression levels and in both squamous and non-squamous tumor histology. Additionally, based on an early descriptive analysis, encouraging overall survival was observed with the combination versus chemotherapy in patients with high TMB ≥10 mut/Mb (HR 0.79; 95% CI: 0.56 to 1.10).”
Drugs that activate the immune system to attack cancer in a process known as immune checkpoint blockade (ICB) are a focus of intense investigation. A number of them are already approved by the U.S. Food and Drug Administration (FDA) for various cancers; namely, the anti-CTLA4 antibody ipilimumab (Yervoy), two anti-PD-1 antibodies: pembrolizumab (Keytruda) and nivolumab (Opdivo), and three anti-PD-L1 drugs: atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These ICB drugs have the potential to induce durable cancer regressions, but the majority of cancer patients just do not respond to them at all.
Biomarkers, signature molecules in the blood or other tissue, can sometimes be used to predict a patient’s response to a given treatment. But no reliable biomarkers exist for ICB, and this is a serious concern. Patients who may really benefit from ICB could be overlooked, and patients who are not likely to respond may receive useless (and very expensive) ICB treatment.
Most potential response predictors that have already been identified are not yet useful for one or all of the following reasons: they are not extensively validated, their significance is still uncertain and may differ from one cancer (or even one patient) to another, or they are technically challenging for routine use. These markers are addressed below. Continue reading…
“The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) improved progression-free survival (PFS) compared with chemotherapy in treatment-naïve patients with high tumor mutation burden (TMB) non–small cell lung cancer (NSCLC).
“Bristol-Myers Squibb (BMS), the manufacturer of both immunotherapies, announced the preliminary findings from part 1a of the phase III CheckMate-227 trial in a press release. The company did not report any further data.”
“Scientists are stepping up the hunt for better diagnostic tests to predict if cancer patients will benefit from costly modern immunotherapy drugs, which are transforming cancer care but remain a hit-and-miss affair.
“Research presented at Europe’s biggest oncology congress in Madrid adds to evidence that patients with an above average number of genetic mutations in their tumors have a better chance of responding to the new treatments, and drugmakers are racing to confirm the idea.”