Translational Science in Oncology: Beyond PD-L1 Expression

The field of Immuno-Oncology (IO) has increasingly focused on PD-1 and PD-L1 inhibitors — and with good reason, given their proven ability in enabling the immune system to fight cancer. However, while PD-L1 expression may help to identify patients more likely to benefit from anti-PD1/PD-L1 therapies, not every patient will respond.

So, what is MedImmune doing about it?

Extensive research is underway at MedImmune to identify biomarkers that can further predict which patients might respond to our medicines, as monotherapy or in combination with other immunotherapies, small molecules, or chemotherapies.

At this year’s American Society of Clinical Oncology (ASCO) meeting, we’re presenting a number of abstracts in which we describe emerging predictive markers.

Some of these include:

  • Interferon gamma (IFNG) signature
    We previously presented a positive correlation between high levels of an IFNG signature that we developed and outcomes in patients with lung cancer treated with our anti-PD-L1 antibody, durvalumab. The new investigational data presented at ASCO takes this a step further, assessing the predictive value of the IFNG signature in patients with bladder cancer, and exploring its relationship to PD-L1 expression. Based on what we observed, our study concludes that an IFNG signature is an additional potential predictive biomarker in bladder cancer patients worthy of further study.
  • Circulating tumor DNA
    We also recently presented clinical data showing that early reduction in variant allele frequencies (VAFs) in circulating tumor DNA (ctDNA) correlated with clinical outcomes in patients with lung cancer treated with durvalumab. At ASCO, we are presenting investigational data that explores that same pattern in patients with bladder cancer treated with durvalumab. Here, we found that ctDNA may be an early predictor of clinical benefit with durvalumab, potentially providing an early signal for how patients may or may not respond to our medicines.
  • Liver metastases
    In this study, the data indicate a correlation of liver metastases and clinical outcomes in lung cancer patients treated with durvalumab, irrespective of PD-L1 status. Thus, liver metastases may be an additional factor to consider when determining when to use anti-PD1/anti-PDL1 therapies.

These, and other investigational data sets being presented at ASCO this year— including additional combination therapies for patients who may not respond to these checkpoint inhibitors—reveal in part what MedImmune scientists are doing to better identify patients who may or may not respond to specific cancer immunotherapies.