Vitrakvi™ (Larotrectinib) Demonstrates Durable Clinical Benefit Beyond Four Years Across All Ages and Tumor Types in TRK Fusion Cancer Patients

• Larotrectinib achieved an overall response rate (ORR) of 75% and a median duration of response (DoR) of 49.3 months in an expanded pooled dataset comprising 206 evaluable adult and pediatric patients with TRK fusion-positive tumors, which arise when an NTRK gene fuses with another unrelated gene, involving 21 differentTumorType, regardless of age, with a longer follow-up period and a median follow-up time of 22.3 months.

• InTumorIn the subgroup analysis, larotrectinib demonstrated rapid and durable responses, as well as prolonged disease control, in patients with lung cancer and primary central nervous system (CNS) TRK fusion cancers.

• Comparisons among patients show that, compared with prior treatment regimens, most TRK fusion-positive patients treated with larotrectinibTumorPatients achieved meaningful clinical benefit.

Berlin, May 19, 2021 — Analyses from four different studies confirm,BayerThe company's precision oncology drug Vitrakvi™(larotrectinib) demonstrates robust and durable clinical efficacy, including rapid and highly sustained responses as well as a favorable safety profile, and is indicated for patients with TRK fusion-positive tumors across all age groups and multiple tumor types. These analyses include the latest long-term efficacy and safety data for non-primary central nervous system (CNS) solid tumors, primary CNS tumors, and lung cancers harboring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Furthermore, a pooled retrospective analysis across patients indicates that the majority of patients with TRK fusion-positive tumors achieved meaningful clinical benefit following treatment with larotrectinib. Vitrakvi is currently the mostBig DataPooled data from the TRK inhibitor with the longest follow-up time (median follow-up: 22.3 months) demonstrated consistent high response rates and response durability exceeding four years in patients of all ages and tumor types with (NTRK) gene fusions. These results will be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, held online from June 4–8, 2021.Tumorpresented at the American Society of Clinical Oncology (ASCO) Annual Meeting.

“MD Anderson Cancer Center Professor of Investigational Cancer Therapeutics, David S. Hong, M.D., said: “We observed that the majority of patients with NTRK gene fusions, including those with central nervous system tumors, can benefit from larotrectinib.” These robust results across all age groups andTumor...provides a clear rationale for patients with specific types of cancer to undergo comprehensive genomic testing, including NTRK 1/2/3 genes, at diagnosis, and offers strong evidence supporting systemic therapy with TRK inhibitors for these patients.”

Dr. Scott Z. Fields, Senior Vice President and Head of Oncology Development at Bayer, said: "Vitrakvi is specifically designed to treat TRK fusion cancers by targeting the cancer drivers responsible for the spread and growth of these tumors, regardless of their location in the body, representing a meaningful advance in the treatment of adult and pediatric patients with TRK fusion cancers. These data demonstrate that, for TRK fusionTumor“For patients, Vitrakvi is an effective and well-tolerated long-term treatment option, demonstrating our commitment to advancing the future of cancer care while delivering real value to both patients and physicians.”

In the expanded pooled dataset, among 206 evaluable adult and pediatric patients with TRK fusion-positive tumors across 21 different tumor typesTumorWith longer follow-up for patients (data cutoff: July 20, 2020), the investigator-assessed overall response rate (ORR) was 75% (95% CI 68–81), including a 22% complete response rate (n=45). For patients with evaluable brain metastases (n=15), the ORR was 73% (95% CI 45–92). Among all evaluable patients, the median follow-up was 22.3 months, and the median duration of response (DoR) was 49.3 months (95% CI 27.3 to not estimable [NE]). At a median follow-up of 22.3 months, the median progression-free survival (PFS) was 35.4 months (95% CI 23.4–55.7), the median overall survival (OS) was not reached, and the 36-month OS rate was 77% (95% CI 69–84).
 
The safety profile was consistent with that previously reported in the overall safety population. The majority of reported treatment-related adverse events (TRAEs) were primarily Grade 1 or 2, with Grade 3 or 4 TRAEs reported in 18% of patients. Only 2% of patients discontinued larotrectinib due to TRAEs, and no treatment-related deaths were reported.
 
The pooled dataset summarizes data from three larotrectinib trials.Clinical Trial(NCT02122913, NCT02576431, and NCT02637687), which enrolled adult and pediatric patients with TRK fusion cancers. This analysis excluded the subset of patients with primary central nervous system cancers.
 
Application of Larotrectinib in Lung Cancer with or without Central Nervous System Metastases (Abstract 9109)

The latest data (as of July 20, 2020) obtained in adult patients with TRK fusion-positive cancers who were heavily pretreated (median of 3 prior lines) showed that larotrectinib exhibits a high degree of anti-# Tumoractivity, demonstrating rapid and durable responses, prolonging survival, and exhibiting a favorable long-term safety profile. Among 15 evaluable patients, the confirmed ORR per investigator assessment was 73% (95% CI 45–92); in evaluable patients with baseline CNS metastases (n=8), the ORR was 63% (95% CI 25–91). Among all evaluable patients (n=15), the 12-month rates for DoR and PFS were 81% and 65%, respectively. At a median follow-up of 16.2 months, the median OS was 40.7 months (95% CI 17.2–NE). TRAEs were reported in 16 patients, with two patients experiencing Grade 3 events. No patients discontinued larotrectinib due to TRAEs. These data are investigator-assessed and from twoClinical TrialPatients enrolled in (NCT02576431, NCT02122913).
 
larotrectinib in primary central nervous systemTumorApplication in (2002 Abstract)

In another summary, two items# Clinical TrialIn the report of (NCT02637687, NCT02576431) (as of July 20, 2020), larotrectinib was evaluated in 33 pediatric and adult patients with primary central nervous system tumors harboring NTRK gene fusions. Among these patients, the ORR was 30% (95% CI 16-49), and 82% of patients with measurable lesions experiencedTumorShrinkage. The 24-week disease control rate was 73% (95% CI 54–87). Median PFS was 18.3 months (95% CI 6.7-NE), median OS was not reached (95% CI 16.9-NE), with a median follow-up of 16.5 months, and the 12-month OS rate was 85% (95% CI 71-99). Three patients experienced grade 3 or 4 TRAEs. No patients discontinued larotrectinib due to TRAEs.
 
larotrectinibClinical TrialComparison Among Patients with TRK Fusion-Positive Cancers (Abstract 3114)

Other larotrectinib data to be presented at the conference include an updated and expanded retrospective analysis of the Growth Modulation Index (GMI), limited to patients enrolled in larotrectinib trials who received at least one prior line of therapy. GMI is a within-patient comparison that uses each patient as their own control, comparing the progression-free survival (PFS) on the current treatment with the time to progression or time to treatment failure (TTP) on the most recent prior therapy. A GMI ratio ≥1.33 has been used as the threshold for meaningful clinical activity. In an extended follow-up analysis of 122 patients (data cutoff: July 2020), nearly three-quarters of patients had a GMI ≥1.33, including six of the nine patients who previously had a GMI ≤1.33 in the earlier analysis. In the expanded ... of 140 patientsBig DataPooled, 74% of patients had a GMI ≥ 1.33. These data are from three prior-line therapy# Clinical Trial(pooled from NCT02122913, NCT02576431, and NCT02637687).
 
About Vitrakvi (larotrectinib)

Vitrakvi™(Larotrectinib) is the first oral TRK inhibitor specifically designed for patients with tumors harboring NTRK gene fusions. This compound has demonstrated high response rates in adult and pediatric patients with TRK fusion-positive tumors, including central nervous system (CNS) tumors, with a duration of response exceeding four years. Larotrectinib has the largest dataset and longest follow-up data among all TRK inhibitors. To date,Clinical TrialStill ongoing, the latest dataset has been published in 《The LancetTumor》 journal, and is scheduled for the upcoming academicConferenceannounce more updated results on.
 
Larotrectinib has been approved in over 40 countries and regions worldwide, including the United States, the European Union, the United Kingdom, and Japan, under the brand name Vitrakvi.®, marketing authorization applications in other regions are ongoing and planned. Larotrectinib has been approved in the European Union for the treatment of adult and pediatric patients with solid tumors harboring neurotrophic receptor tyrosine kinase (NTRK) gene fusions, which are locally advanced, metastatic, unresectable, or associated with suboptimal surgical outcomes, and who have no satisfactory alternative treatment options.
 
As of February 2019Eli LillyThe company to LoxoTumorThrough the acquisition, Bayer obtained the exclusive license rights for the global (including the United States) development and commercialization of larotrectinib and selitrectinib (BAY 2731954), an investigational TRK inhibitor currently in clinical development.
 
About TRK FusionTumor

TRK fusion tumors are caused by the fusion of an NTRK gene with another unrelated gene, resulting in the production of aberrant TRK proteins. These aberrant proteins, also referred to as TRK fusion proteins, are constitutively active and lead to sustained overactivation of downstream cellular signaling pathways. Regardless of the primary tumor site, these TRK fusion proteins promote tumor growth and spread. TRK fusion tumors are not restricted to specific tissue types and can occur in various locations throughout the body. The incidence of TRK fusion tumors varies widely across a range of adult and pediatric solid tumors, including lung cancer, thyroid cancer, gastrointestinal cancers (colorectal cancer, cholangiocarcinoma, pancreatic cancer, and appendiceal tumors), sarcomas, central nervous system tumors (gliomas and glioblastomas), salivary gland carcinomas (mammary analogue secretory carcinoma), and pediatricTumor(Infantile fibrosarcoma and soft tissue sarcoma).
 
About BayerTumor`Business Unit`

Guided by its mission of "Science For A Better Life," Bayer continuously optimizes its innovative product portfolio. We are driven by the passion and determination to develop innovative medicines that help cancer patients improve and extend their lives. Bayer's Oncology division currently includes six oncology products and several other compounds in various stages of clinical development. Bayer focuses its research activities on cutting-edge scientific platforms, including precision molecular oncology, targeted alpha therapy, and immuno-oncology. Across our key focus areas, we offer several marketed and developmental prostate cancer therapies designed to extend survival while minimizing treatment-related side effects for patients at different disease stages. Another strategic priority for Bayer is precision oncology, which includes an approved TRK inhibitor specifically indicated for tumors harboring NTRK gene fusions, a gene that isTumoroncogenic drivers of tumor growth and metastasis; as well as another TRK inhibitor in development. The company prioritizes research approaches focused on targets and signaling pathways capable of transforming cancer treatment paradigms.
 
# About Bayer

As a multinational enterprise, Bayer possesses core competencies in health and agriculture within the life sciences sector. The company is dedicated to helping people overcome the major challenges posed by a growing and aging global population through its products and services, thereby fostering human well-being and the prosperity of the planet. Bayer is committed to advancing sustainability and generating a positive impact on its business. At the same time, the Group enhances profitability and creates value through technological innovation and business growth. Worldwide, the Bayer brand stands for trust, reliability, and quality. In fiscal year 2020, Bayer employed approximately 100,000 people and reported sales of EUR 41.4 billion. Research and development expenditure, excluding special items, amounted to EUR 4.9 billion. For more information, visit www.bayer.com.
 
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