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Bayer to Highlight Clinical Data on Vitrakvi® (larotrectinib) and Research on Investigational AhR Inhibitor at AACR 2020 Virtual Meeting

BusinessWire

Abstracts: CT199, 10363, DDT01-02

WHIPPANY, N.J.–(BUSINESS WIRE)–Bayer announced additional clinical trial results for Vitrakvi® (larotrectinib) and latest research on its investigational small molecule aryl hydrocarbon receptor (AhR) inhibitor BAY 2416964 to be presented at the upcoming American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting I from April 27-28, 2020. Data at this meeting underscore Bayer’s continued efforts to explore the potential of clinical stage projects in oncology from the laboratory to clinical practice and share the latest study progress with the scientific community. The original AACR program will be presented in segments in two AACR Virtual Annual Meetings, with the first part taking place from April 27-28. Access to AACR Virtual Annual Meeting I will be made freely available. More details can be found here. The abstracts of these proffered paper presentations will be posted online at 12:01 a.m. EDT on Monday, April 27.

“We are committed to making our potentially practice-changing research on treatment approaches available to doctors and to people living with cancer,” said Scott Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. “Bayer’s approach to cancer research includes investing in drug development and testing programs designed to help ensure that the right patients get the right treatment. At AACR, we will share important clinical trial analyses that help inform the selection of patients who may be eligible for our TRK inhibitor Vitrakvi. In addition, Bayer will also share research on a potential new approach in immuno-oncology.”

Two analyses from the Vitrakvi clinical trials will be shared. The first analysis includes a Plenary Session presentation on Vitrakvi efficacy and safety data based on the presence of neurotrophic receptor tyrosine kinase (NTRK) gene fusions or other alterations, and the second includes data on outcomes in patients with TRK fusion cancer by prior therapy and performance status. Vitrakvi is approved in the U.S., Canada, Brazil and the European Union (EU). In the U.S., Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Additional filings in other regions are underway or planned.

At the virtual meeting, for the first time, the structure and functional characterization of the investigational small molecule AhR inhibitor BAY 2416964 will be presented. The AhR receptor is expressed in many different immune cells and is considered to play an important role in immuno-suppression within the tumor microenvironment. An AhR inhibitor such as BAY 2416964 is thought to reactivate anti-tumor immune responses in a manner distinct from currently approved checkpoint inhibitors, and thus may provide a new approach for cancer immunotherapy. BAY 2416964 is currently investigated in a first-in-human, Phase I trial in patients with advanced solid malignancies. Immuno-oncology (IO) is a key area of research for Bayer.

Presentations for the Virtual Annual Meeting I are listed below:

Presentations:

About Vitrakvi® (larotrectinib)1

Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have an 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.

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%).

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.

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.

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.

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.

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.

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%).

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.

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

Please see the full Prescribing Information for VITRAKVI® (larotrectinib).

About Bayer’s Oncology Research Platforms

Bayer focuses its research activities on first-in-class innovations across the following scientific platforms: Oncogenic Signaling, Targeted Alpha Therapies, and Immuno-Oncology. In the field of Oncogenic Signaling the company is developing small molecules and other modalities to target crucial pathways of intracellular tumor signaling that are responsible for the development and survival of cancer in well-defined patient populations identified using selection biomarker. In regard to Targeted Alpha Therapies drug candidates are being developed using the company’s proprietary Thorium-227 platform for delivering high-energy alpha-radiation via different targeting molecules such as antibodies to tumor cells. In Immuno-Oncology Bayer is developing next-generation treatments that intervene at different levels of the cancer immunity cycle specifically addressing patients not responding to immune checkpoint inhibitors.

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 now expands to 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.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to www.bayer.com.

© 2020 Bayer

BAYER, the Bayer Cross, and Vitrakvi are registered trademarks of Bayer.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References

  1. VITRAKVI [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2019.

PP-PF-ONC-US-1142-1 04/20

Contacts

Media Contact:
Rose Talarico, Tel. +1 862.404.5302

E-Mail: rose.talarico@bayer.com

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