Roche (OTCQX:RHHBY) has been able to achieve impressive preliminary results from its phase 1b study using a triple-combination with Tecentriq to treat patients with advanced triple-negative breast cancer (TNBC). This excitement builds upon prior FDA approval for a Tecentriq combination to treat patients with TNBC, however, for whose tumors express PD-L1 status. While the results from the new study are very early evidence of efficacy, it shows that the combination can obtain a strong objective response rate (ORR). Roche has a sharp advantage in the immuno-oncology space over Merck (MRK), for the time being, when it comes to the TNBC population.
The trial being done was a phase Ib study that recruited patients with front-line advanced TNBC. Patients were treated with a triple-combination regimen, which consisted of ipatasertib, Tecentriq, and chemotherapy. Chemotherapy could be given either as paclitaxel or nab-paclitaxel (Abraxane). It was shown that patients treated with this triple-combination were able to obtain an ORR of 73%. That means confirmed responses were observed in 19 out of 26 patients. There are two reasons why one should take these results with a grain of salt, in my opinion. The first reason is that this is a small group of patients. Eventually, clinical studies have to be completed with much larger patient populations. That means data produced based on these 26 total patients may not come out with a similar ORR in a group of hundreds of patients. The second reason is that the trial is only in a phase Ib study. There are still a few studies before this drug can be brought up to the FDA for approval. I feel these results are quite solid though. Especially when you take a look at the mechanism of action of the drug mixed in with Tecentriq and chemotherapy. This third drug is known as ipatasertib. Ipatasertib is an AKT inhibitor and plays a major role in combating against tumors. The goal for this drug is to inhibit all 3 isoforms of AKT. Why is it important to add ipatasertib into this combination to treat patients with advanced TNBC? That's because Aberrant or abnormal AKT signaling is responsible for causing resistance to apoptosis (cell death). It is also responsible for cell growth, metabolism, and proliferation (cell division and growth). The bottom line is that it is responsible for tumor growth. An AKT inhibitor works to counteract all these issues. This makes a lot of sense why a 73% ORR was achieved along with Tecentriq and chemotherapy. It's important to note that responses were achieved in this patient population despite biomarker status of the tumor. Why would there be a claim that ipatasertib has such a profound effect in a combination with Tecentriq and chemotherapy? That's because when the PI3K/AKT pathway has been activated, it enables tumors to become resistant to chemotherapies and hormonal therapies. With ipatasertib in place to counter this issue, you can see how it helps to allow the immune system to go after the tumor without a lot of resistance. Ipatasertib even has a prominent role in undoing checkpoint inhibitor resistance against PTEN. PTEN is a negative regulator of AKT, which is able to place a resistance against checkpoint inhibitor therapy. Investors won't have to wait that long for the next study, Roche intends to initiate a double-blind phase 3 study using this triple-combination therapy later in 2019.
The latest results are very good news for Roche because it has an opportunity to potentially offer a better therapy for these TNBC patients. That's because the company has already received approval in March of 2019 for a Tecentriq combination. However, this was a Tecentriq plus chemotherapy (nab-paclitaxel) combination to treat unresectable locally advanced or metastatic TNBC patients whose tumors express PD-L1. As you can see, with this approval, patients had to have tumors that expressed PD-L1. With the latest triple-combination therapy of Tecentriq, it can treat TNBC patients regardless of biomarker tumor status. That would expand the market opportunity for treating this indication. Roche has done well in the breast cancer population; however, Merck has a huge hold in the immuno-oncology space. Its drug Keytruda generated $7 billion in sales last year. This compares to Roche's Tecentriq only generating $765 million. Then, there is the risk of Merck potentially becoming a major competitor in the TNBC space itself. That's because it has two studies of its own to treat this patient population. There is Keynote-119 using Keytruda alone, and then Keynote-522 using Keytruda in combination with chemotherapy to treat patients with TNBC.
Roche has made substantial progress in achieving positive phase 1b results using its triple combination Tecentriq therapy in patients with advanced TNBC. The risk is that this program is still in the early stages of clinical development. That means it will be some time before it gets to a late-stage study and, ultimately, possibly approved. The good news is that Tecentriq plus Abraxane was already approved as a combination to treat patients with unresectable locally advanced or metastatic PD-L1-positive TNBC. A triple combination may end up being superior in efficacy compared to the double. Another risk involves the clinical trials that Merck is running. It has two ongoing studies that are testing Keytruda alone and in combination with chemotherapy for the very same TNBC population. I believe that Roche should be in good shape for now because its triple-combination, while early, appears to have achieved a substantial objective response rate for this patient population.
This article is published by Terry Chrisomalis, who runs the Biotech Analysis Central pharmaceutical service on Seeking Alpha Marketplace. If you like what you read here and would like to subscribe to, I'm currently offering a two-week free trial period for subscribers to take advantage of. My service offers a deep-dive analysis of many pharmaceutical companies. The Biotech Analysis Central SA marketplace is $49 per month, but for those who sign up for the yearly plan will be able to take advantage of a 33.50% discount price of $399 per year.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.