MyPathway is studying drugs that are already FDA approved in the US but for non-approved indications. The idea is that these drugs have shown evidence and safety that they are effective in certain tumour types but what MyPathway is trying to do is to study these drugs in non-approved tumour types but which have similar molecular alterations to the cancer types in which they are already approved.
Can you tell us some of the design for the MyPathway trial?
MyPathway is a multi-basket study and it initially involved four baskets, it now has six baskets and eight drugs and it’s based on the premise that the biology of a tumour and the molecular pathway of a tumour can be targeted therapy.
What drugs are involved in each basket?
The HER2 basket involves Herceptin and Perjeta. We have a BRAF basket that involves vemurafenib and cobimetinib. We have an EGFR basket with erlotinib, a Hedgehog basket with vismodegib, a cancer immunotherapy basket with atezolizumab and an ALK basket with alectinib. So we started with four baskets and then because we have an overarching protocol we can add or subtract baskets. So the two baskets that were added were the cancer immunotherapy basket with atezolizumab and the ALK basket with alectinib.
How are the results looking so far?
Most of our data comes from the HER2 basket, so two-thirds of our enrolment is patients with HER2 alterations. Most of those have HER2 amplifications and we’re seeing very strong signals in our HER2 amplified patients with many tumour types. Particularly we have quite a large population with HER2 amplified colorectal cancer and in those patients if they have K-ras wild-type HER2 colorectal cancer they have a response rate of 52% and their duration of response is quite long. These are very heavily pre-treated patients and they have a ten month duration of response.
We’re also seeing signals in HER2 salivary cancer that are pretty amazing, on the order of about 70% response rate. It’s a rare tumour but we often see HER2 amplification in salivary patients as well. We have signals in HER2 biliary cancer and HER2 bladder cancer.
What is so important about K-ras signalling?
K-ras and a lot of other studies that are exploring colorectal cancer do think that the K-ras mutated population is a driver and potentially has a poorer prognosis. So in patients who have K-ras mutated and HER2 amplified colorectal cancer, they don’t seem to benefit. A lot of other ongoing studies of HER2 amplified colorectal cancer are excluding patients who are K-ras mutated.
How do the timelines look for each basket?
For the atezolizumab basket, that one just recently was added and we fortunately have been able to bring in more patients to MyPathway. We’re almost at 500 patients now and we’re adding 100 more patients so the total n will be 600. We’re shunting most of those patients to the atezolizumab or cancer immunotherapy basket. So we think future data will come from this cancer immunotherapy basket.
What are your thoughts on being ‘tumour agnostic’?
It’s interesting, this idea of tumour agnostic and the FDA is starting to bring forth guidance documents and we’re starting to realise that in multiple tumour types our HER2 agents are working. So we’ve had good results with a dual HER2 blockade – Herceptin Perjeta. We don’t know if this data will be something that the FDA would think of approving at some point but we think that we have enough evidence to take some of this data to NCCN guidelines where we might submit it to multiple different committees like the colorectal committee and the head and neck committee for salivary and maybe the hepato-biliary committee.
How are you deducing what to try in combination?
The combinations that we’re studying in MyPathway – Herceptin, Perjeta – we think there’s a lot of biologic rationale to combining them. Vemurafenib and cobimetinib also has some biologic rationale to combining them. We’re just trying to follow the evidence and the science.