For Immediate Release

Bayer presents new analyses for Vitrakvi® (larotrectinib) in adult and pediatric patients with TRK fusion cancer with solid tumors, and new data in primary central nervous system tumors and brain metastases

Annual Meeting of the American Society of Clinical Oncology (ASCO) 2019

- In children with TRK fusion cancer, the overall response rate (ORR) was 94% per investigator assessment (n=32/34), with median duration of response (DOR) not reached(1)

- In adults with TRK fusion cancer, the ORR was 68% per independent assessment (n=44/65), and 76% per investigator assessment (n=56/74) with median DOR not reached(2)

- New data include NTRK gene fusion positive patients with primary central nervous system (CNS) tumors and across solid tumors with brain metastases; ORR was 60% in evaluable patients with brain metastases (n=3/5)(3)

- Quality of life (QoL) was analyzed with Vitrakvi treatment in both children and adults(4)

- Majority of adverse events (AEs) were grade 1 or 2(1,2)

Abstracts: 10010; 3122; 2006; 6602

WHIPPANY, N.J., May 15, 2019 /PRNewswire/ -- Bayer today announced findings from new analyses and data for Vitrakvi® (larotrectinib), which 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.5 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.

(PRNewsfoto/Bayer)

In the analysis of children with TRK fusion cancer, there was an ORR of 94% as per investigator assessment using RECIST 1.1, with median DOR not reached at the time of data cut-off of July 30, 2018. In the analysis of adult patients with TRK fusion cancer, a response rate of 68% as per independent assessment and 76% as per investigator assessment was seen using RECIST 1.1, and with median follow up of 17.5 and 17.2 months, respectively, the median DOR had not been reached at time of data cut-off (July 30, 2018). New data on patients with primary central nervous system (CNS) tumors of various histologies or brain metastases will be presented as part of an oral presentation. An analysis on quality of life (QoL) with Vitrakvi treatment was also conducted in both children and adults with TRK fusion cancer. Adverse events seen with the new data for adults and children were mostly grade 1-2.1,2,3,4 The full data from these analyses will be presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2019, taking place in Chicago, Illinois from May 31June 4, 2019.

"These data further confirm the efficacy and safety of larotrectinib in patients with TRK fusion cancer, regardless of tumor type and age, including those who present with brain metastases or primary CNS tumors," said Douglas S. Hawkins, M.D., hematology/oncology division chief at Seattle Children's Hospital and professor of pediatrics at the University of Washington School of Medicine. "It underscores the urgency for widespread genomic testing to identify patients."

"These latest data add to the body of evidence for larotrectinib in patients with TRK fusion cancer," said Scott Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer's Pharmaceutical Division. "With our commitment to developing treatments like larotrectinib as well as the investigational TRK inhibitor BAY 2731954, we are demonstrating our commitment to researching and advancing the future of cancer care, while providing true value for patients and physicians."

Vitrakvi Presentations and Posters

Data from pediatric patients from the expanded dataset show an ORR of 94% (n=32/34) with Vitrakvi as per investigator assessment using RECIST 1.1, including 12 complete responses (CR), 18 confirmed partial responses (PR) and 2 PR pending confirmation.1 At the time of data cut-off (July 30, 2018), the median DOR had not been reached (range 1.6+ to 26.7+ months). (Oral Presentation 10010, Session: Pediatric Oncology II; Sunday, June 2, 8:12AM8:24AM (CDT), Room: S504)

Data in adult patients from the expanded dataset show an ORR of 68% as per independent assessment (n=44/65), including a 17% CR and 51% PR, and 76% by investigator assessment (n=56/74) with a 9% CR, 57% confirmed PR, and 9% PR pending confirmation.2 At the time of data cut-off (July 30, 2018), the median DOR had not been reached. (Poster Presentation 3122, Session: Developmental Therapeutics and Tumor Biology (Nonimmuno); Saturday, June 1, 8:00AM11:00AM (CDT), Room: Hall A)

An analysis across clinical trials of TRK fusion cancer patients with evaluable brain metastases (n=5) shows an ORR of 60% per investigator assessment using RECIST 1.1.3 Additional data will be provided in an oral presentation at ASCO on June 3, 2019. (Oral Presentation 2006, Session: Central Nervous System Tumors; Monday, June 3, 3:15PM3:27PM (CDT), Room: S102)

An evaluation on patient-reported outcomes is also being presented.4 (Poster Presentation 6602, Session: Health Services Research, Clinical Informatics, and Quality of Care; Saturday, June 1, 1:15PM4:15PM (CDT), Room: Hall A)

About Vitrakvi® (larotrectinib) 
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 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.5 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.

Research suggests that the NTRK gene can become abnormally fused to other genes, producing a TRK fusion protein that can act as an oncogenic driver, promoting cell growth and survival in tumor cell lines.5

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%).5

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.5

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.5

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.5

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.5

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.5

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%).5

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.5

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.5

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

About TRK Fusion Cancer
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein.5 The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade.5 These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless to where it originates in the body.5 TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body.5 TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).5,6

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 five 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 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to www.bayer.us.

© 2019 Bayer
BAYER, the Bayer Cross and Vitrakvi are registered trademarks of Bayer.

Media Contact:
Rose Talarico, Tel. +1 862.404.5302
E-Mail: rose.talarico@bayer.com

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 Van Tilburg, C; Dubois, S, Albert, C et al. Larotrectinib Efficacy and Safety in Pediatric TRK Fusion Cancer Patients. American Society of Clinical Oncology 2019; June 2, 2019. Chicago, Illinois. Abstract 10010.
2 Hong, D; Kummar, S; Farago, A et al. Larotrectinib Efficacy and Safety in Adult TRK Fusion Cancer Patients. American Society of Clinical Oncology 2019; June 1, 2019. Chicago, Illinois. Abstract 3122.
3 Drilon, A; DuBois, S; Farago, A et al. Activity of Larotrectinib in TRK Fusion Cancer Patients with Brain Metastases or Primary Central Nervous System Tumors. American Society of Clinical Oncology 2019; June 3, 2019. Chicago, Illinois. Abstract 2006.
4 Kummar, S; Mascarenhas, L; Geoerger, B et al. Patient-Reported Outcomes from Two Global Multicenter Clinical Trials of Children and Adults with Tropomyosin Receptor Kinase (TRK) Fusion Cancer Receiving Larotrectinib. American Society of Clinical Oncology 2019; June 1, 2019. Chicago, Illinois. Abstract 6602.
5 Vitrakvi® (larotrectinib) capsules and solution for oral use [Prescribing Information]. Stamford, CT: Loxo Oncology Inc.; November 2018.     
6 Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34.

PP-LAR-US-0839-1                                                                                                               05/19

Intended for U.S. Media

SOURCE Bayer