Bayer to Present Key Data Across Oncology Portfolio Showcasing Significant Advances in Cancer Care at 2022 ASCO Annual Meeting 

• Prostate cancer remains a key focus area with NUBEQA® (darolutamide) investigational data in non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC), and Xofigo® (radium Ra 223 dichloride) research in metastatic castration-resistant prostate cancer (mCRPC)

• Presentations of Vitrakvi® (larotrectinib) include long-term efficacy and safety data for patients with TRK fusion cancer from integrated and expanded analyses, updated health-related quality of life (QoL) of patients with TRK fusion cancer and sub-analyses for TRK fusion cancer patients with primary central nervous system (CNS) tumors and lung cancer, respectively

• Investigator-initiated research (IIR) featuring Stivarga® (regorafenib) and Nexavar® (sorafenib) will also be displayed

Abstracts: 5078, 5044, TPS5111, 5038, 5040, 5041, 10030, 3100, 9024, 2010, 6563, 6597, 10006, 4060, 3561, TPS11585, 4125, 11555, 12040

—Intended for U.S. Media Only–

WHIPPANY, N.J.–(BUSINESS WIRE)–Bayer will present new data across its oncology portfolio at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting from June 3-7, 2022. These presentations continue to reinforce Bayer’s position as an innovator in oncology and ongoing dedication to advancing oncology treatments for patients on a global scale.

NUBEQA^® (darolutamide) data presented will include overall survival (OS) and prostate-specific antigen (PSA) results from the investigational Phase III ARASENS trial in metastatic hormone-sensitive prostate cancer (mHSPC) and results of a post-hoc analysis from the Phase III ARAMIS trial in non-metastatic castration-resistant prostate cancer (nmCRPC). NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. NUBEQA is indicated in the U.S. for the treatment of men with nmCRPC.¹ The U.S. Food and Drug Administration (FDA) has recently accepted a supplemental New Drug Application (sNDA) and granted Priority Review for NUBEQA in combination with docetaxel for the treatment of mHSPC.

Research on Xofigo^® (radium Ra 223 dichloride) will also be highlighted, including results from an interim analysis of the RALU study, which evaluated safety and survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177-prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) after Xofigo. Additionally, alkaline phosphatase (ALP) decline and OS data in mCRPC patients treated with Xofigo in the REASSURE study will be presented. Xofigo is indicated for the treatment of patients with mCRPC, symptomatic bone metastases, and no known visceral metastatic disease.²

Efficacy and safety findings of Vitrakvi^® (larotrectinib) for patients with TRK fusion cancer from an integrated pooled analysis per an independent review committee (IRC) assessment, efficacy and safety data from an expanded dataset, updated health-related quality of life (QoL) of adult and pediatric patients with TRK fusion cancer, and sub-analyses for TRK fusion cancer patients with primary central nervous system (CNS) tumors and lung cancer, respectively, will be shared. Additional data for Vitrakvi include an analysis in adult and pediatric patients evaluating Vitrakvi compared to standard of care using a matching-adjusted indirect comparison (MAIC). MAIC is an alternative method for comparative data when a randomized control trial (RCT) is not available and/or possible, as for a rare condition like TRK fusion cancer.³ Results from these studies further support Vitrakvi’s existing clinical profile in TRK fusion cancer across a variety of tumor types and ages. 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 (ORR) and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.⁴

Other research includes investigator-initiated research (IIR) for Stivarga^® (regorafenib) and Nexavar^® (sorafenib) in several areas of oncology.

Presentations from Bayer projects for the 2022 ASCO Annual Meeting are listed below:

Darolutamide

• Abstract title: Association of prostate-specific antigen (PSA) response and overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 3 ARASENS trial
  • Abstract 5078; June 6, 2:15pm EDT
• Abstract title: Progression patterns by types of metastatic spread, prostate-specific antigen (PSA), and clinical symptoms: Post-hoc analyses of ARAMIS
  • Abstract 5044; June 6, 2:15pm EDT
• Abstract title: Open-label study of androgen receptor inhibition with darolutamide plus androgen-deprivation therapy (ADT) versus ADT in men with metastatic hormone-sensitive prostate cancer using an external control arm (ARASEC) – Trial in Progress (TiP)
  • Abstract TPS5111; June 6, 2:15pm EDT
• Abstract title: Influence of darolutamide on cabazitaxel systemic exposure – Investigator-Initiated Research (IIR)
  • Abstract 5038; June 6, 2:15pm EDT

Radium-223 dichloride (Ra-223)

• Abstract title: Safety and survival outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177-prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) after radium-223 (²²³Ra): Interim analysis of the RALU study
  • Abstract 5040; June 6, 2:15pm EDT
• Abstract title: Alkaline phosphatase (ALP) decline and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the REASSURE Study
  • Abstract 5041; June 6, 2:15pm EDT

 

Larotrectinib

• Abstract title: Efficacy and safety of larotrectinib in pediatric patients with tropomyosin receptor kinase (TRK) fusion-positive cancer: An expanded dataset
  • Abstract 10030; June 6, 9:00am EDT
• Abstract title: Long-term efficacy and safety of larotrectinib in a pooled analysis of patients with tropomyosin receptor kinase (TRK) fusion cancer
  • Abstract 3100; June 5, 9:00am EDT
• Abstract title: Updated efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer
  • Abstract 9024; June 6, 2:15pm EDT
• Abstract title: Long-term control and safety of larotrectinib in a cohort of adult and pediatric patients with tropomyosin receptor kinase (TRK) fusion primary central nervous system (CNS) tumors
  • Abstract 2010; June 5, 12:30pm EDT
• Abstract title: Updated health-related quality of life of patients with TRK-fusion cancer treated with larotrectinib in clinical trials
  • Abstract 6563; June 6, 2:15pm EDT
• Abstract title: Overall survival (OS) of patients with TRK fusion-positive cancer receiving larotrectinib versus standard of care (SoC): A matching-adjusted indirect comparison (MAIC) using real-world data (RWD)
  • Abstract 6597; June 6, 2:15pm EDT
• Abstract title: Securing access to innovative anticancer therapies for children, adolescents and young adults outside clinical trials: The SACHA study of the French Society of Pediatric Oncology (SFCE) – Investigator-Initiated Research (IIR)
  • Abstract 10006; June 6, 5:36pm EDT

Regorafenib

• Abstract title: REGOMUNE: A phase II study of regorafenib plus avelumab in solid tumors—Results of the oesophageal or gastric carcinoma (OGC) cohort – Investigator-Initiated Research (IIR)
  • Abstract 4060; June 4, 9:00am EDT
• Abstract title: Regorafenib (REGO) plus FOLFIRINOX as frontline treatment in patients (pts) with RAS-mutated metastatic colorectal cancer (mCRC): A phase I/II, dose-escalation and dose-expansion study – Investigator-Initiated Research (IIR)
  • Abstract 3561; June 4, 9:00am EDT
• Abstract title: REGOMAIN: A randomized, placebo-controlled, double-blinded, multicenter, comparative phase II study of the efficacy of regorafenib as maintenance treatment in patients (pts) with high-grade bone sarcomas (HGBS) at diagnosis or relapse and without complete remission after standard treatment – Investigator-Initiated Research (IIR); Trial in Progress (TiP)
  • Abstract TPS11585; June 5, 9:00am EDT
• Abstract title: REGOMUNE: Phase II study of regorafenib plus avelumab in solid tumors—Results of the gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) cohort – Investigator-Initiated Research (IIR)
  • Abstract 4125; June 4, 9:00am EDT
• Abstract title: Activity of regorafenib in patients with non-adipocytic soft tissue sarcoma (NASTS): Evaluation of heterogeneity of treatment effect on the updated analysis of pooled cohorts – Investigator-Initiated Research (IIR)
  • Abstract 11555; June 5, 9:00am EDT

Sorafenib

• Abstract title: Deficit Accumulation Frailty Index (DAFI) scores and acute myeloid leukemia outcomes – Investigator-Initiated Research (IIR)
  • Abstract 12040; June 4, 2:15pm EDT 

About NUBEQA^® (darolutamide)¹

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.¹

On July 30, 2019, the FDA approved NUBEQA^® (darolutamide) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral NUBEQA in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of NUBEQA orally twice daily in combination with androgen deprivation therapy (ADT) or ADT alone. The primary efficacy endpoint was metastasis-free survival (MFS). NUBEQA is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating NUBEQA plus ADT versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov.

Developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, NUBEQA is indicated for the treatment of men with nmCRPC.¹ The approvals of NUBEQA for nmCRPC in the U.S., European Union (EU), and other global markets have been based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of NUBEQA plus ADT compared to ADT alone.¹ Filings in other regions are underway or planned.

INDICATION FOR NUBEQA^® (darolutamide)

NUBEQA^® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

IMPORTANT SAFETY INFORMATION FOR NUBEQA^® (darolutamide)

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs 11%), pain in extremity (6% vs 3%) and rash (3% vs 1%).

Clinically significant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs 3.4% on placebo) and heart failure (2.1% vs 0.9% on placebo).

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the prescribing information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Xofigo^® (radium Ra 223 dichloride) Injection²

Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Important Safety Information for Xofigo^® (radium Ra 223 dichloride) Injection

Warnings and Precautions:

• Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression–notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia–has been reported in patients treated with Xofigo.

  Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure

• Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be ≥1.5 × 10⁹/L, the platelet count ≥100 × 10⁹/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 10⁹/L and the platelet count ≥50 × 10⁹/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care

• Concomitant Use With Chemotherapy: Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued

• Increased Fractures and Mortality in Combination With Abiraterone Plus Prednisone/Prednisolone: Xofigo is not recommended for use in combination with abiraterone acetate plus prednisone/prednisolone outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of Xofigo in combination with abiraterone acetate plus prednisone/prednisolone in 806 asymptomatic or mildly symptomatic mCRPC patients, an increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received Xofigo in combination with abiraterone acetate plus prednisone/prednisolone compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone. Safety and efficacy with the combination of Xofigo and agents other than gonadotropin-releasing hormone analogues have not been established

• Embryo-Fetal Toxicity: The safety and efficacy of Xofigo have not been established in females. Xofigo can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with Xofigo

Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations

Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia

Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo

Secondary Malignant Neoplasms: Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow-up for patients on the trial

Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the Xofigo group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy

Adverse Reactions: The most common adverse reactions (≥10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%)

Please see the full Prescribing Information for Xofigo (radium Ra 223 dichloride).

About Vitrakvi^® (larotrectinib)⁴

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%).

Contacts

Media Contact:
Sue Ann Pentecost, Tel +1 910.221.6446

Email: [email protected]

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