Combinations and personalized healthcare most powerful hits to cancer


Edward Bradley, MD

While not the official theme for this year’s meeting of the American Society of Clinical Oncology (ASCO), personalized healthcare (PHC) dominates the various presentations.

For oncology, PHC is especially potent because of the number of genetic mutations that could be targeted by drugs. Take PHC a step further and add combination therapeutics and companion diagnostics to the mix of cancer treatment, and what we have is a formula for powerful medicine.

That is precisely what we’ve been working toward here at MedImmune and AstraZeneca. For more than two decades, our goal has been to understand the biology of disease and how we can identify it at the patient level—making medicine personal for patients. Oncology is a core therapeutic area in which we’ve made significant breakthroughs.

Increased potential for anti-PDL1s
At last year’s ASCO annual meeting, we were excited to talk about MEDI4736—our investigational human monoclonal antibody (mAb) directed against programmed cell death ligand 1 (PD-L1). We know that signals from PD-L1 help tumors avoid detection by the immune system and that MEDI4736 blocks those signals, thus countering a tumor’s immune-evading tactics and empowering the patient’s own immune system.

This year, we’ll be sharing new data that support the enormous potential of this investigational molecule across cancer types as both monotherapy and in combination treatments. In particular, we have even more confidence in MEDI4736 as a cornerstone for our studies of our novel combination treatments. That’s because of the encouraging early data we have on the clinical activity of MEDI4736 combined with other immuno-oncology and small molecule investigational medicines for different cancers. This includes the results of trials with MEDI4736 and tremelimumab, regardless of PD-L1 biomarker status, as well as the potential of MEDI4736 in combination with AZD9291 and with both BRAF and MEK inhibitors.

More specifically, we’ll present the following data and other information:

  • Safety and efficacy of MEDI4736 in combination with tremelimumab in patients with non-small cell lung cancer (NSCLC).
  • Safety and efficacy of the triple combination of MEDI4736 and BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in patients with advanced melanoma.
  • An open-label study of MEDI4736 in combination with MEDI0680—another of our investigational anti-PD-L1 mAbs—in patients with advanced malignancies.
  • Dose escalation data from a Phase I study of MEDI4736 in combination with gefitinib, AstraZeneca’s epidermal growth factor receptor (EGFR) mutation- positive tyrosine kinase inhibitor (TKI) in advanced NSCLC.
  • Preliminary results from TATTON, a multi-arm Phase Ib trial of AZD9291 combined with MEDI4736, AZD6094 or selumetinib in EGFR-mutant lung cancer patients who have progressed following therapy with an EGFR-TKI.

In addition, we’ll present updates that reinforce the durability of MEDI4736 as monotherapy in patients with NSCLC and in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), as well as the development of a PD-L1 companion diagnostic assay. This test—jointly developed by Ventana Medical Systems and MedImmune—has shown robust, reproducible results as a biomarker to predict response to MEDI4736.

We believe that combination approaches can have a tremendous impact on cancer treatment, including overcoming some of the resistance and unresponsiveness that we have seen with some immuno-oncology approaches in the past.

The challenge lies in identifying which combinations will work best in which patients. This is where PHC and companion diagnostics may propel the future of cancer therapeutics, further unlocking the benefits of immuno-oncology for a greater number of patients across all tumor types and tumor biology.