On September 28, 2019 Bayer reported that 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 (Press release, Bayer, SEP 28, 2019, View Source [SID1234553278]). 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 44th European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019, taking place September 27 to October 1 in Barcelona, Spain.

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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 (Free ESMO Whitepaper) 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.