A multi-histology basket trial of ado-trastuzumab emtansine in patients with HER2 amplified cancers

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Published: 2 Jun 2018
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Dr Bob Li - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Li speaks with ecancer at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss early results from a trial of anti-HER2 ado-trastuzumab emtansine in HER-2 amplified tumours detected in sites beyond breast and gastric diseases.

He outlines the trial design and recruitment scheme, in which evidence of response in a small patient cohort led to further recruitment in that indication.

Among these early results, Dr Li contrasts the total lack of response in HER-2 amplified colorectal tumours to the 100% response rate in salivary tumours, and discusses further trial expansion to further validate these findings.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

This is a basket trial and it’s targeting a biomarker called HER2 amplification. This is identified through next generation sequencing, so through genetic analysis. The structure of the trial is that the patients are identified through NGS and they are then treated with the same drug, irrespective of where the tumour comes from. We are specifically studying cancers other than breast and gastric for which there are approved HER2 targeted agents. So this includes lung cancers, endometrial cancers, bladder cancers, salivary cancers, colorectal cancers and other tumours. Patients are then treated with the same medicine, that’s ado-trastuzumab emtansine, or TDM-1, that is FDA approved in breast cancer, HER2 positive breast cancer. They’re given the same dose – 3.6mg/kg every three weeks intravenously until progression of disease.

For each cohort we would accrue seven patients and if there’s no response of the first seven we would then close that cohort but if there’s one or more response we would then expand that cohort to at least eighteen patients in total and we would have to see five responses in eighteen to reject the novel [?] hypothesis. So that’s the study design.

How are the results coming along?

The early result that was just presented at this meeting, it’s very promising, it showed clinical efficacy across a variety of solid tumours. The overall response rate was 28% in 57 evaluable patients. We recruited 62 patients altogether across a variety of solid tumours other than breast and gastric. Those patients were mostly heavily pre-treated with multiple lines of chemotherapy, up to seven prior lines of chemotherapy. We saw good efficacy, especially in lung cancer, with three out of seven patients had a confirmed partial response and durable responses. We saw a 25% response rate in heavily pre-treated HER2 amplified endometrial cancers. Those patients really don’t have an approved targeted therapy so really a patient population of unmet need. We saw five out of twenty patients with confirmed both partial responses and also complete responses that lasted two or more years. We also saw 100% response in the six patients with HER2 amplified salivary gland cancers. All of them responded and many of them are still going, approaching one year and beyond.

We also looked at other diseases that didn’t respond. So colorectal cancers, we treated seven patients, no response. Bladder cancers we treated three patients, no response. This may be due to genetic heterogeneity with concurrent genetic alterations like KRAS and NRAS. Also this could be differences in chemosensitivity of different tumour types because TDM-1, or ado-trastuzumab emtansine, is really a molecule that’s a targeted molecule but that has a chemotherapy that’s linked to it. So that could play a role but also it could be just small sample sizing in that particular subset of disease.

Overall, the early results are very promising showing clinical efficacy across many other disease types if they have HER2 amplification.

And what does the timeline look like for any final results, any milestones we should be on the lookout for?

So because of this promising early data that just got presented we are expanding the trial to get more patients. This includes HER2 amplified lung cancers, we’d like to accrue at least twenty patients, and also HER2 amplified salivary gland cancers, the one that had a 100% response rate so far, we’d like to accrue more than twenty patients to get more mature data. This could be really a breakthrough in cancer therapy for these patients in need.