Bayer Announces Updated Analysis for Vitrakvi® (larotrectinib) Demonstrating High Response Rate and Duration of Response of Nearly Three Years in Adults and Children with TRK Fusion Cancer

- New data cut-off confirmed Vitrakvi is the only TRK inhibitor to demonstrate an overall response rate (ORR) of nearly 80 percent in an expanded population of more than 150 patients, including an ORR of 75 percent in patients with brain metastases(1)

- Vitrakvi achieved median progression free survival of 28.3 months and median overall survival of nearly four years(1)

- Data represent the largest and longest-term data for any TRK inhibitor, including the broadest range of tumor types and ages studied(1)

Abstract: 445PD

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Bayer

Sep 28, 2019, 03:00 ET

WHIPPANY, N.J., Sept. 28, 2019 /PRNewswire/ -- Updated clinical data for Vitrakvi^® (larotrectinib) in adult and pediatric patients with TRK fusion cancer demonstrated an overall response rate (ORR) of 79 percent (n=121; 95% CI, 72–85), including 16 percent complete responses (CR) and 63 percent partial responses (PR) per investigator assessment. In 12 evaluable patients with brain metastases, the ORR was 75 percent (n=9; 95% CI, 43–95, all PR).¹ These results build on Vitrakvi's original pooled analysis and now include 153 evaluable patients (data cut-off of February 19, 2019), making this the largest dataset of any TRK inhibitor to date.¹ Vitrakvi demonstrated a median duration of response (DOR) of 35.2 months (n=108 confirmed responses; 95% CI, 22.8–NE) and key secondary endpoints showed a median progression free survival of 28.3 months (95% CI, 22.1–NE) and a median overall survival of 44.4 months (95% CI, 36.5–NE), with 88 percent (95% CI, 83–94) of patients still alive at one year after the start of therapy.¹ These data were presented in a poster discussion at the 44^th European Society for Medical Oncology (ESMO) Congress 2019, taking place September 27 to October 1 in Barcelona, Spain.

Vitrakvi is approved in the U.S. 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 ORR and DOR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.² Vitrakvi is also approved in the European Union, Canada and Brazil.

"As we continue to study the efficacy and safety of larotrectinib across a wide range of solid tumor types and ages, including patients with CNS tumors, it is encouraging to see the consistency in larotrectinib's responses in patients with TRK fusion cancer," said David Hyman, M.D., chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center. "The responses we have seen with larotrectinib underscore the need to test our patients for genomic alterations, such as NTRK gene fusions, to provide them with meaningful treatment options."

The safety data presented at the ESMO 2019 Congress encompassed the entire Vitrakvi safety database in cancer patients (N=260). The majority of adverse events (AE) reported were grade 1 or 2 for AEs that occurred at any grade in at least 15 percent of patients, or at grade 3 or 4 in at least three percent of patients.¹

"With a patient population that is now three times our initial analysis, Vitrakvi continues to demonstrate impressive efficacy," said Scott Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer's Pharmaceutical Division. "We are committed to bringing Vitrakvi to patients around the world, as demonstrated through the recent approvals in multiple global markets."

About Vitrakvi^®(larotrectinib)
Vitrakvi^® (larotrectinib) 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.²

Following the acquisition of Loxo Oncology by Eli Lilly and Company in February 2019, Bayer has obtained the exclusive licensing rights for the global development and commercialization, including in the U.S., for Vitrakvi and the investigational TRK-inhibitor selitrectinib (previously BAY 2731954 and LOXO-195) progressing through clinical development.

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%).²

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.²

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.²

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.²

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.²

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.²

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%).²

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.²

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.²

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.² The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade.² These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless of where it originates in the body.² TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body.² 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).^2,3

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 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.com.

Media Contact:
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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.

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¹ Hyman, David M., van Tilburg, Cornelis M., Albert, Catherine M., et al. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. European Society of Clinical Oncology 2019; September 28, 2019. Barcelona, Spain. Abstract 445PD.
² Vitrakvi® (larotrectinib) capsules and solution for oral use [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2019.
³ 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.

SOURCE Bayer