AL3818 hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma

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Published: 10 Jun 2021
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Prof Brian Van Tine - Washington University in St. Louis, St. Louis, USA

Prof Brian Van Tine speaks to ecancer in an online interview for the virtual ASCO 2021 meeting about the APROMISS trial.

This was a phase III trial evaluating AL3818 (catequentinib, anlotinib) hydrochloride monotherapy compared with dacarbazine in subjects with metastatic or advanced synovial sarcoma.

He reports that the progression free survival for catequentinib bettered dacarbazine with the safety profile comparable to similar drugs in the field.


Catequentinib is a multi-tyrosine kinase inhibitor that is being developed within the field of sarcoma. There is a three-arm phase III clinical trial ongoing of which we reported the first arm that matured. The first arm that matured was within the synovial sarcoma cohort where we did a randomised arm looking at catequentinib versus dacarbazine for which we found a statistically significant progression free survival and the tail of the curve which had a prolonged duration in a subset of patients, suggesting that this is an active agent for the treatment of synovial sarcoma. In addition, we found that prior pazopanib use did not affect the outcomes of catequentinib, suggesting we may have a second tyrosine kinase inhibitor available for the treatment of synovial sarcoma.

This study was an intention to treat randomised phase III with a 2:1 ratio. For every two patients that got catequentinib one patient was randomised to dacarbazine. Patients that were randomised to dacarbazine at progression could then go on to catequentinib, thus overall survival would not be a read-out of this study.

The key results were as follows. The progression free survival of catequentinib was better than dacarbazine which is an active comparator. The tail of the curve was much better for catequentinib than it was for dacarbazine. The safety profile of catequentinib was much simpler than, say, comparable drugs in our field such as pazopanib and with no hepatotoxicity, our main findings being diarrhoea, hypothyroidism and hypertension which are common for the class. Taken together we are hoping that this will allow for another tyrosine kinase inhibitor to become available for the treatment of synovial sarcoma. We await the readout of the other two randomised arms looking at leiomyosarcoma and alveolar soft part sarcoma.

Catequentinib is oral and to have a second oral agent which a lot of us feel is quite tolerable available to patients that will give them an opportunity to not have to come in for IV chemotherapy, so we will have a second chance to try to find a tyrosine kinase inhibitor that’s active for synovial sarcoma in the journey that they are on. We’re hoping that by having one or two choices, hopefully most patients would potentially respond to both. We would have that same idea as we have with GIST where we go from one tyrosine kinase inhibitor to another, in that case it’s c-KIT. Within synovial sarcoma it’s actually unknown what we’re hitting; these are broad spectrum tyrosine kinase inhibitors and so we’re hoping that the activity of catequentinib when added to this [?? 2:38] journey which allows you to stay off IV chemotherapy.

One of the things that’s important to point out is that to do a three-arm randomised histology-focussed clinical trial within sarcoma is actually the right way to do it so that you’re not mixing too many histologies at once. This is why we’re beginning to read out arms of this trial that are positive.