MedImmune has expanded the clinical trial protocol for its ongoing Phase I study investigating the safety and efficacy of monalizumab in combination with durvalumab for patients with metastatic colorectal cancer (CRC).

MedImmune, the R&D arm of AstraZeneca, partnered with immuno-oncology specialist Innate Pharma to examine of the drug combination in patients with advanced solid tumours. Innate contributes monalizumab, its first-in-class anti-NKG2A monoclonal antibody, while AstraZeneca brings durvalumab, its anti-PD-L1 immune checkpoint inhibitor.

The trial’s protocol has been expanded, with new cohorts added testing monalizumab in combination with both durvalumab and standard-of-care treatment in patients with first and second line CRC.

The dose-escalating portion of the study has already been completed, while the expansion cohorts in selected advanced solid tumours are ongoing.

The primary objective of the new study arms will be safety, with secondary outcome measures being overall response rate and duration of response, among others.

“We are delighted that our partner MedImmune has decided to further expand the colorectal patient population,” Innate chief medical officer Pierre Dodion said. “We look forward to the first clinical data read-outs from the Phase I study and initial expansion cohort programme during 2018.”

CRC is the third most commonly diagnosed cancer, with the World Health Organisation (WHO) estimating that worldwide there are 1.65 million new cases and 835,000 deaths each year. At diagnosis 21% of cases are metastatic, though as in many instances the disease progresses, estimates raise to around 50% following diagnosis.

Durvalumab blocks the interaction of the protein PD-L1 with receptors PD-1 and CD80, countering the immune-evading tactics of tumours and releasing the inhibition of immune responses. The drug is being investigated as a monotherapy and a combination treatment for a number of other diseases such as small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

Monalizumab targets NKG2A receptors on tumour-infiltrating cytotoxic NK and CD8 T lymphocytes. The drug may re-establish an anti-tumour response mediated by NK and T cells, as well as enhance the cytotoxic potential of other therapeutic antibodies.

Monalizumab is currently the only checkpoint inhibitor capable of acting simultaneously on T and NK cells, as well as tumour-infiltrating immune cells, offering a more effective immune response.

Innate Pharma currently has four first-in-class antibodies at a clinical stage, including its treatment for cutaneous T-cell lymphomas IPH4102, which is currently in a Phase I trial stage. The company also has a range of preclinical candidates and technologies in its pipeline.