WHIPPANY, N.J.--(BUSINESS WIRE)-- Updated clinical data for Vitrakvi^® (larotrectinib) show continued high response rates and duration of response with longer follow-up and consistent safety in an expanded data set of 116 adult patients with tropomyosin receptor kinase (TRK) fusion cancer, including those with brain metastases. A separate descriptive analysis evaluated quality of life (QoL) measures for adult and pediatric patients, including infants younger than 2 years, using clinical questionnaires. These findings are being presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program, held from May 29-31, 2020.

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 a neurotrophic receptor tyrosine kinase (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. 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. Additional filings in other regions are underway or planned.

“With more patients added and a longer follow-up, we continue to see efficacy and a consistent safety profile for larotrectinib, regardless of tumor types, in adult patients with solid tumors harboring a TRK fusion. In addition, new data provide an understanding of quality of life results for the majority of adults, children and infants with TRK fusion-positive cancers treated with larotrectinib,” said Alexander Drilon, M.D. Acting Chief of Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York, USA. “These data underscore the importance of routine genomic testing for people diagnosed with cancer, so that we can identify and match appropriate patients with the right treatment approach.”

Updated data with a cut-off of July 15, 2019 in 116 adult patients with TRK fusion cancer across 17 tumor types showed an overall response rate (ORR) per investigator assessment of 71 percent (95 percent CI 62–79) with 10 percent complete responses (CRs) and 60 percent partial responses (PRs) (2 percent pending confirmation). For patients with brain metastases (n=14), the ORR was 71 percent (95 percent CI 42–92) with 10 patients having partial responses. The median duration of response was 35.2 months (95 percent CI 21.6–not estimable [NE]) at a median follow-up of 17.4 months. The median progression-free survival was 25.8 months (95 percent CI 15.2–NE) at a median follow-up of 14.6 months. The rate of overall survival (OS) at ≥ 12 months was 87 percent.¹ In the primary data set at the time of FDA approval, Vitrakvi demonstrated an ORR of 75 percent (n=55) (95 percent CI, 61-85) by independent review committee, including a 22 percent CR rate and 53 percent PR rate across various solid tumors harboring a TRK fusion in adults and children (n=55). The median duration of response was not yet reached (range 1.6+ to 33.2+) (n=44).

“These analyses add to the breadth of data including long-term follow-up with Vitrakvi, supporting its use as an efficacious treatment for adults and children with TRK fusion cancer,” said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. “Our continued study of cancers caused by genomic alterations underscores our commitment to developing treatments like Vitrakvi for patients and the physicians who serve them.”

The safety profile was consistent with that of the overall safety population previously reported. The majority of adverse events (AEs) reported were grade 1 or 2. One patient (1 percent) discontinued due to a larotrectinib-related AE. No treatment-related grade 3 or 4 AEs occurred in more than 3 percent of patients and no treatment-related deaths were reported.¹

In an additional analysis, QoL data were collected from the larotrectinib trials using EORTC QLQ-C30 (adults) and PedsQL (children) questionnaires, and were analyzed descriptively and longitudinally. The proportion of patients above 2 years with normal or above and below normal QoL scores, compared to values in the literature for the U.S. general population, was also calculated. QoL scores for most patients ≥2 years were either maintained within or moved into the normal range during larotrectinib treatment.²

Data for both these analyses presented at ASCO were pooled from three larotrectinib clinical trials (NCT02122913, NCT02576431 and NCT02637687) in adult and pediatric patients with TRK fusion cancer.²

Dr. Alexander Drilon has provided compensated advisory services to Bayer.

About Vitrakvi^® (larotrectinib)³

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.

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 TRK Fusion Cancer

TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. 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. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. 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).

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.us.

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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. Drilon, AE, Farago, AF, et al. Activity and safety of larotrectinib in adult patients with TRK fusion cancer: An expanded data set [poster]. In: ASCO Meeting Library: ASCO; 2020. Abstract 3610; Poster 340.
2. Kummar, S, Van Tilburg, CM, et al. Quality of life of adults and children with TRK fusion cancer treated with larotrectinib compared to the general population [abstract]. In: ASCO Meeting Library: ASCO; 2020. Abstract 3614.
3. VITRAKVI [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2019.

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