On May 29, 2019 Bayer AG and Foundation Medicine, Inc. reported a global collaboration for the development and commercialization of NGS-based companion diagnostics (Press release, Foundation Medicine, MAY 29, 2019, View Source [SID1234536644]). This agreement allows for collaboration across multiple oncology drug candidates and approved therapies developed by Bayer and covers Foundation Medicine’s full portfolio of tests, including FoundationOneCDx. The first project will be to develop a companion diagnostic for Vitrakvi (larotrectinib), the first and only TRK inhibitor approved in the U.S. for patients with TRK fusion cancer across all solid tumors.

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In the United States, Vitrakvi is approved 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 that 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.1 This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

NGS based companion diagnostic tests aim to unlock molecular information from each patient’s tumor genome to guide treatment decisions for cancer therapies. FoundationOneCDx is the first FDA-approved broad companion diagnostic for all solid tumors2.

"We are excited to collaborate with Foundation Medicine to develop new companion diagnostics and provide tools to move to a more personalized treatment approach," said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "The development of a companion diagnostic for Vitrakvi, and our broader collaboration with Foundation Medicine, is an important step forward toward expanding access to testing and identifying the right treatment options for patients with cancer."

"Foundation Medicine is proud to collaborate with Bayer to develop multiple companion diagnostics including a companion diagnostic for Vitrakvi," stated Cindy Perettie, Foundation Medicine’s Chief Executive Officer. "It is imperative that patients receive broad comprehensive genomic profiling at initial diagnosis of late stage cancer to determine if they are eligible for these medicines."

Financial terms of the agreement were not disclosed.

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.5