On June 4, 2021 Bayer reported that it is presenting study results at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting being held online June 4-8, 2021 (Press release, Bayer, JUN 4, 2021, View Source [SID1234583613]).
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In particular, Bayer is presenting four abstracts related to its Vitrakvi (larotrectinib) across TRK fusion cancer patients of all ages, ranging from 0.1 to 84 years, and for multiple tumor types. Vitrakvi is a first-in-class TRK inhibitor for TRK and presenters are supporting the drug’s effectiveness in a range of cancers with TRK gene fusions regardless of tissue type or patient age.
Scott Fields, Head Senior Vice President, Oncology Development, Bayer Global, and Hendrik Nogai, Vice President, Global Development Lead NTRK Program, SBU Oncology, Bayer, took time out ahead of ASCO (Free ASCO Whitepaper) to speak with BioSpace about the drug and the upcoming presentations.
The four specific presentations look at long-term efficacy and safety of the drug in an integrated dataset of TRK fusion cancer patients; long-term results of the drug in patients with TRK fusion lung cancer; intra-patient comparison of Vitrakvi clinical trials in TRK fusion cancer, which is an expanded dataset; and results of the drug in adults and children with TRK fusion-positive primary tumors of the central nervous system.
Fields emphasizes that Vitrakvi is not tissue specific, but works on a particular type of gene fusion known as neurotrophic receptor tyrosine kinase (NTRK), or just TRK. It received accelerated approval from the U.S. Food and Drug Administration (FDA). With the accelerated approval pathway, drugs for serious conditions that fill an unmet medical need can be approved based on a surrogate endpoint, which allows them to get on the market faster. That surrogate endpoint is often a laboratory measurement, radiographic imagine, physical sign or other measure that is believed to predict clinical benefit but is not by itself a measure of clinical benefit. Then, the company continues to conduct studies to verify the drug’s efficacy and safety.
"TRK fusion cancers can come from the liver, they can come from the pancreas, they can come from the brain. It’s more about the mutation," Fields said. "It’s not about which tissue it comes from. And this is the first time ever that a tumor has been defined by a mutation, not by the histologic tissue. It drives the cancer. And when we block it with Vitrakvi, you see responses that are really quite extraordinary."
For example, the studies they are presenting indicate a 75% overall response rate (ORR) that is very durable. Fields says the overall survival time "hasn’t even been reached at forty-nine months."
The expanded data has a longer follow-up with 206 adult and pediatric patients that could be evaluated. They had TRK fusion cancer across 21 different tumor types. Out of that 75% ORR, 22% were complete responses. For the patients with brain metastases, the ORR was 73%. The median duration of response (DoR) was 49.3 months at a median follow-up of 22.3 months.
"We not only confirmed the data, but even seemed to improve on it," Nogai said. "So we see longer durability of the responses and the responses rate is even increasing with time."
The 22% complete responses in solid tumors, Nogai added, "is quite remarkable, and with the long follow-up, we have a median duration of response of 49 months. This is almost unheard of."
The additional data also suggests a very good safety profile, even though "the patients may remain on treatment for many years," according to Nogai.
One of the presentations also shows the drug’s activity in patients with central nervous system metastases. The data presented includes an updated and extended retrospective growth modulation index (GMI) analysis limited to patients enrolled in Vitrakvi trials with at least one previous line of therapy. GMI is a retrospective intra-patient comparison that utilizes the patient as their own control by comparing PFS on current therapy to time to progress or treatment failure (TTP) on the most recent previous therapy.
"This was one area of uncertainty. We did not have a lot of patients with CNS disease. But now, with the expanded dataset, we can see that it is an active drug," Nogai said.
Updated data with a cut-off of July 20, 2020, is being presented on heavily pre-treated adult patients with TRK fusion with lung cancer. The patients received a median of three previous therapies. The data demonstrated the drug’s consistent response rates with longer follow-up.
"The response rate in these fifty patients is around 73% again," Nogai said. "Remarkable durability at 34 months in patients that is still ongoing, and with a PFS of 35 months."
Both Fields and Nogai emphasized that Vitrakvi is turning out to be effective in children and adults with TRK fusion cancers.
"We should mention that we do have a liquid formulation. So even the very, very young patients can receive this, as well as older patients," Fields said. "It’s very important to ensure that patients are getting tested for TRK fusions, because Vitrakvi is demonstrating really good activity in these patients across cancer types and different ages."
There are several ways to test for the gene fusions, with the most easy and affordable being immunohistochemistry (IHC), although there are also next-generation sequencing (NGS) tests and PCR as well, which are more expensive, and typically used for confirmation. The results of these studies present a strong argument for comprehensive genomic testing that includes NTRK 1/2/3 genes for patients, to better understand what is driving the cancer and to appropriately match them with the right treatment approach.
Fields notes, "This is an inexpensive way to look for patients, but it always has to be confirmed. NGS is the standard for confirmation but is quite expensive and not routinely performed. However, correct diagnosis is one of the most important things we’re doing. Doctors really need to be aware of this. You need the pediatric oncologist to understand it and the oncologists focused on adults or specific cancers. This drug represents a meaningful advancement in the treatment of both adult and pediatric patients with TRK fusion cancer, regardless of where they originate in the body."