Updated Vitrakvi® (larotrectinib) Sub-Analysis at ATA 2021 Supports Efficacy and Safety in Adult and Pediatric TRK Fusion Thyroid Cancer Patients

• Overall response rate (ORR) of 71% (95% confidence interval [CI] 51—87) among those with all types of thyroid cancers (n=28), 86% (95% CI 64—97) among patients with differentiated thyroid cancer (DTC; n=22) and 29% (95% CI 4—71) among patients with anaplastic thyroid cancer (ATC; n=7)¹
• Overall median time to response was 1.9 months (range: 1.6—3.7) and with a Kaplan-Meier estimated 24-month duration of response (DoR) of 81% (95% CI 60—100)¹
• Two patients (7%) had Grade ≥3 treatment-related adverse events (TRAEs) and none discontinued treatment due to AEs¹

Presentation: Oral 15

WHIPPANY, N.J.--(BUSINESS WIRE)--Updated thyroid sub-analysis of 29 adult and pediatric TRK fusion cancer patients, of which 28 were evaluable, treated with Vitrakvi^® (larotrectinib) showed notable overall response rates (ORR) and duration of response (DoR). With longer follow-up (data cut-off July 20, 2020) the ORR in 28 evaluable patients was 71% (95% CI 51—87) for all histologies (with 2 [7%] complete responses and 18 [64%] partial responses) and the ORR was 86% (95% CI 64—97) for patients with differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancers. Among 7 patients with anaplastic thyroid cancer (ATC), the ORR was 29% (95% CI 4—71).¹ These data were presented in an oral presentation on October 2, 2021 from 12:00 – 1:00 PM EST at the virtual American Thyroid Association 2021 Annual Meeting.

Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have a 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. Patients should be selected for therapy based on a Food and Drug Administration (FDA)-approved test. 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

“Being one of the more common solid tumors, thyroid cancer – specifically papillary thyroid cancer – has one of the highest NTRK fusion prevalence rates of up to 25%,³ especially in younger patients,” said Steven G. Waguespack, M.D., Professor of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center. “In patients with thyroid cancer who harbor an NTRK gene fusion and who require systemic therapy for advanced disease, these data support larotrectinib’s potential as an appropriate treatment option.”

Among all patients with thyroid cancer, overall median time to response was 1.9 months (range 1.6—3.7). Kaplan-Meier estimated 24-month rate for DoR was 81% (95% CI 60—100). Two patients (7%) had Grade 3 TRAEs and no patients discontinued treatment due to adverse events. This analysis pooled data from three Vitrakvi clinical trials (NCT02122913, NCT02576431 and NCT02637687) in adult and pediatric patients with TRK fusion cancer.¹

“With three years of follow-up and an expanded patient population, these results provide additional evidence to support Vitrakvi's use in NTRK gene fusion-positive thyroid cancer,” said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer's Pharmaceutical Division. “These data in patients with thyroid cancer further underscore the importance of integrating biomarker-driven oncology medicines into cancer care, so that appropriate patients can potentially benefit from a targeted treatment approach.”

About Vitrakvi^® (larotrectinib)

Vitrakvi^® (larotrectinib) is indicated 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 will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

Select patients for therapy based on an FDA-approved test.

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)

Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances.

In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients.

Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption.

Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients.

Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption.

Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption.

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 dosage when resumed.

Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients.

Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures.

Hepatotoxicity: In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) 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. VITRAKVI 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%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%).

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 a chimeric TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins are oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer. 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 and rectal, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (including secretory carcinoma of the salivary gland) and pediatric cancers (infantile fibrosarcoma and other soft tissue sarcomas).^2,5

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 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 help people and planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2020, the Group employed around 100,000 people and had sales of 41.4 billion euros. R&D expenses before special items amounted to 4.9 billion euros. For more information, go to www.bayer.com.

^© 2021 Bayer
BAYER, the Bayer Cross, and Vitrakvi are registered trademarks of Bayer.

Find more information at www.pharma.bayer.com
Our online press service is just a click away: media.bayer.com
Follow us on Facebook: www.facebook.com/pharma.bayer
Follow us on Twitter: https://twitter.com/BayerPharma

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. Waguespack S. et al. Long-term Efficacy and Safety of Larotrectinib in Patients with Advanced TRK Fusion-positive Thyroid Carcinoma [abstract]. ATA 2021 Presentation Oral 15.
2. Vitrakvi® [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; March 2021.
3. Amatu A, Sartore-Bianchi A, Bencardino K, Pizzutilo EG, Tosi F, Siena S. Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer. Ann Oncol. 2019;30(Suppl_8):viii5-viii15. doi:10.1093/annonc/mdz383.
4. American Thyroid Association. Anaplastic Thyroid Cancer. https://www.thyroid.org/anaplastic-thyroid-cancer/. Accessed August 2021.
5. 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-PF-VIT-US-0873-1 9/21

Intended for U.S. Media Only

Bayer Media Contact:
Carolyn Nagle, Tel. +1 201.419.0337
E-Mail: carolyn.nagle@bayer.com