On May 14, 2020 Bayer and ArcherDX, Inc. reported a global collaboration for the development and commercialization of a next-generation sequencing (NGS)-based companion diagnostic (CDx) for Vitrakvi (larotrectinib) (Press release, Bayer, MAY 14, 2020, View Source [SID1234558073]). The primary objective of the collaboration is to broaden patient access to comprehensive genomic testing inclusive of neurotrophic receptor tyrosine kinase 1 (NTRK1), NTRK2 and NTRK3 gene fusions and to help improve identification of appropriate treatment options for patients with TRK fusion cancer which can lead to meaningful treatment options.
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Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic tropomyosin receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Genomic cancer testing helps detect changes in a tumor’s DNA, called genomic profiling, that can determine how the cancer behaves and why it grows or spreads.2 Almost 50 percent of patients who undergo genomic cancer testing may have actionable genomic alterations, meaning the alterations can be matched to treatments that have been approved or are in clinical trials.3,4 Genomic cancer testing has already impacted patient cancer care in both common and rare malignancies. This has allowed for the identification of personalized treatment options.5 However, studies show that only a small percentage of cancer patients undergo such testing.5 It is therefore critical that testing becomes part of routine clinical practice to help guide treatment choice.
"In order to help more patients to benefit from Vitrakvi, broader access to high quality testing via next-generation sequencing is of key importance," said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "The collaboration with ArcherDX perfectly complements Bayer’s CDx strategy and fits our ambition to provide the right treatment to the right patients with cancer."
"Barriers currently exist that inhibit the broad adoption of genomic testing to inform treatment decisions. A kit-based CDx that is tumor agnostic and detects all NTRK gene fusions will enable high-quality genomic testing to be deployed in regional and community settings, where 85 percent of cancer patients receive care.6 For these patients, our technology provides RNA-based profiling for the detection of actionable fusions across known and novel NTRK fusion partners," said Jason Myers, Chief Executive Officer and co-founder, ArcherDX. "We are pleased to collaborate with Bayer to address their medical need and accelerate access to therapy."
NGS-based CDx tests aim to unlock molecular information from each patient’s tumor genome to guide treatment decisions for cancer therapies. ArcherDX is developing and pursuing regulatory clearances for an in vitro diagnostic (IVD), a comprehensive NGS-based therapy selection product that utilizes Archer’s proprietary Anchored Multiplex PCR (AMP) technology to measure clinically relevant genomic mutations for tumor profiling and CDx from both tissue and blood.
ArcherDX and Bayer are developing a kit-based CDx to detect NTRK gene fusions, including NTRK1, NTRK2 and NTRK3 for Vitrakvi and plan to seek approval in different markets, including the European Union (EU), U.S. and Japan. The CDx version of this panel will allow local laboratories to provide referring physicians with potentially actionable genomic information, so that appropriate patients can be matched to specific therapeutic options based on their genomic findings.
The Pharmaceuticals Business Development & Licensing team of Bayer facilitated this collaboration. Financial terms of the agreement were not disclosed.
About Vitrakvi (larotrectinib)
Vitrakvi (larotrectinib) is a first-in-class TRK inhibitor for TRK fusion cancer across solid tumors. Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic tropomyosin receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Vitrakvi is approved in several markets, including the U.S., EU, Canada and Brazil.
TRK fusion cancer is rare overall, affecting no more than a few thousand patients across the U.S. and Europe. It affects both children and adults and occurs in varying frequencies across various solid tumor types. TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. These TRK fusion proteins act as oncogenic drivers that fuel the spread and growth of the patients’ cancer, regardless of where it originates in the body.
Important Safety Information for VITRAKVI (larotrectinib)
Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurologic adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).1
Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.1
Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.1
Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.1
Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.1
Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.1
Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).1
Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.1
Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.1
Please see the full Prescribing Information for VITRAKVI (larotrectinib).
About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.