Durvalumab plus tremelimumab or durvalumab monotherapy in metastatic urothelial carcinoma

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Published: 9 Feb 2018
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Dr Guru Sonpavde - Dana-Farber Cancer Institute, Boston, USA

Dr Sonpavde speaks with ecancer at the 2018 ASCO Genitourinary Cancers Symposium about the STRONG trial, which will look at the use of of fixed-dose durvalumab tremelimumab or durvalumab monotherapy in advanced solid malignancies. 

He outlines that despite initial high response rates to current standard of care first-line chemotherapy, most patients with locally advanced or metastatic urothelial carcinoma eventually experience disease progression.

With no defined standard of care second-line therapies, prognosis remains poor, though immunotherapy offers hope.

When the durvalumab monotherapy cohort is established, the study will look at a fixed dose of durvalumab in combination with tremelimumab, also to be given at a fixed dose every 4 weeks.

The STRONG study is specific where we have the trial still ongoing is a study looking at durvalumab alone, that's a PD-L1 inhibitor alone, or in combination with tremelimumab. It's not a randomised study, it's a PET cohort. The novel feature of this study is that the durvalumab is being given in a fixed dose and the other novelty is it's every four weeks. So ordinarily so far durvalumab is approved in the advanced bladder cancer, urothelial cancer setting in post-platinum patients as a q two weeks, every two weeks, dosage and it's weight based at 10mg/kg every two weeks. So in this study we have ongoing which is a phase IIIb expansion study, it's a safety and feasibility study, a fixed flat dosing of durvalumab once every four weeks, not every two weeks, so it simplifies the dosage. The reason they're doing that is they found that the trough level of durvalumab, the pharmacokinetics, is very well captured across different weights of patients with this flat dose every four weeks which makes it more convenient for patients and more convenient for physicians to remember this flat dosing instead of a weight based dosing.

So far it is premature to give the results of this study because the study is still ongoing. Preliminarily this kind of flat dosing every four weeks seems to achieve the pharmacokinetics of the minimum trough level of durvalumab which is required for its pharmacodynamic activity inhibiting PD-L1 on the tumour cell. Once we finish the durvalumab cohort in this study, we achieve the safety and feasibility demonstration of that, we then move on to the cohort of durvalumab plus tremelimumab which is a CTLA-4 inhibitor, the combined immunotherapy approach, again using a flat fixed dosing of tremelimumab every four weeks.

The adverse events of durvalumab are well known, there is a small risk of immune adverse events - the colitis, pneumonitis, hepatitis, so we have to watch for that; endocrinopathies like hypothyroidism, skin rash, so we watch for that. And of course this study with the fixed flat dosing every four weeks is trying to establish that the safety of this q every four weeks dosing with the flat dosing achieves a comparable safety profile compared to the every two weeks dosing.