Bayer Presents Latest Data and New Research to Advance Cancer Care within Oncology Portfolio at 2021 ASCO Annual Meeting 

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  • Updated long-term efficacy and safety data of Vitrakvi® (larotrectinib) for patients with TRK fusion cancer from an integrated dataset, sub-analyses for TRK fusion cancer patients with primary central nervous system (CNS) tumors and lung cancer, respectively, as well as updated results from an intra-patient comparison to be featured
  • In prostate cancer, a key therapeutic area for Bayer, investigator-initiated research (IIR) on Xofigo® (radium Ra 223 dichloride) in combination with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) will be highlighted with data from the ongoing PEACE-III study; four additional presentations, including several IIRs, to be presented
  • Additional research on tolerability of NUBEQA® (darolutamide) from extended follow-up in the Phase III ARAMIS trial in non-metastatic castration-resistant prostate cancer (nmCRPC) will be presented
  • IIR data from the ODENZA trial exploring patient preferences between NUBEQA and enzalutamide in men with mCRPC to also be featured
  • Data across other disease states in Bayer’s growing oncology portfolio with Aliqopa® (copanlisib), Stivarga® (regorafenib) and Nexavar® (sorafenib) will also be presented

    Abstracts: 3108, 2002, 9109, 3114, 5079, 5046, 5002, 5036, TPS5093, TPS5091, TPS5493, 7510, 4078, 3560, 3030 

WHIPPANY, N.J.–(BUSINESS WIRE)–Bayer will present new data across its oncology portfolio at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from June 4-8, 2021. Bayer’s presence at the meeting underscores the company’s commitment to ongoing research that maximizes the utility of existing treatments and development of new therapies to broaden the impact for oncology patients in need.

Updated long-term efficacy and safety findings of Vitrakvi® (larotrectinib) for patients with TRK fusion cancer from an integrated dataset, sub-analyses for TRK fusion cancer patients with primary central nervous system (CNS) tumors and lung cancer, respectively, as well as updated results from an intra-patient comparison from Vitrakvi clinical trials will be shared. These data build upon the existing clinical profile for Vitrakvi in patients with solid tumors harboring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. 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 an 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.

Follow-up data on tolerability and treatment response from the Phase III ARAMIS trial of NUBEQA® (darolutamide) in non-metastatic castration-resistant prostate cancer (nmCRPC) and investigator-initiated research (IIR) featuring an exploration of patient preferences between NUBEQA and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC) will also be presented. The data from the extended follow-up analysis add to the established clinical profile for NUBEQA in patients with nmCRPC, including a proven tolerability profile.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. NUBEQA is indicated in the U.S. for the treatment of men with nmCRPC.

Additional research highlighting Xofigo® (radium Ra 223 dichloride), including IIR, will also be showcased. Of note, five presentations in ongoing Phase I-IV trials, most notably an oral presentation from the ongoing PEACE-III study, where Xofigo is being researched in combination with enzalutamide, will be featured. Xofigo is indicated for the treatment of patients with mCRPC, symptomatic bone metastases and no known visceral metastatic disease.

Subset data from the Phase III trial CHRONOS-3 evaluating the investigational combination of Aliqopa® (copanlisib) and rituximab compared to rituximab and placebo in relapsed follicular lymphoma (FL) or marginal zone lymphoma (MZL) evaluating the combination therapy across different types of relapsed indolent non-Hodgkin’s Lymphoma (iNHL). Results from CHRONOS-3 were recently published in The Lancet Oncology.2 In 2017, Aliqopa was approved for the treatment of adult patients with relapsed FL who have received at least two prior systemic therapies based on the results of a single arm, multi-center, Phase II clinical trial (CHRONOS-1).3 Accelerated approval was granted for this indication based on ORR. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial.

Data from Stivarga® (regorafenib) and Nexavar® (sorafenib) will explore new treatment approaches in several difficult-to-treat tumors, potentially investigating the use of these treatments in broader patient populations.

Notable presentations from Bayer projects for the 2021 ASCO Annual Meeting are listed below:

Larotrectinib

  • Abstract title: Long-term efficacy and safety of larotrectinib in an integrated dataset of patients with TRK fusion cancer

    • Abstract 3108; June 4, 9:00am EDT
  • Abstract title: Efficacy and safety of larotrectinib in adult and pediatric patients with tropomyosin receptor kinase (TRK) fusion-positive primary central nervous system tumors

    • Abstract 2002; June 7, 8:00am EDT
  • Abstract title: Long-term efficacy and safety of larotrectinib in patients with TRK fusion lung cancer

    • Abstract 9109; June 4, 9:00am EDT
  • Abstract title: Intra-patient comparison from larotrectinib clinical trials in TRK fusion cancer: An expanded dataset

    • Abstract 3114; June 4, 9:00am EDT

Darolutamide

  • Abstract title: Darolutamide (DARO) tolerability from extended follow up and treatment response in the Phase 3 ARAMIS trial

    • Abstract 5079; June 4, 9:00am EDT
  • Abstract title: ODENZA: A French prospective, randomized, open-label, multicenter, cross-over phase II trial of preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (CRPC) – Investigator-Initiated Research (IIR)

    • Abstract 5046; June 4, 9:00am EDT

Radium-223 dichloride (Ra-223)

  • Abstract title: Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis – Investigator-Initiated Research (IIR)

    • Abstract 5002; June 8, 8:00am EDT
  • Abstract title: Biomarker analysis of phase (Ph) IB trial of radium-223 (Rad) and niraparib (Nira) in patients (Pts) with metastatic castrate-resistant prostate cancer (mCRPC)(NiraRad) – Investigator-Initiated Research (IIR)

    • Abstract 5036; June 4, 9:00am EDT
  • Abstract title: Radium-223 (Ra-223) versus novel antihormone therapy (NAH) for progressive metastatic castration-resistant prostate cancer (mCRPC) after 1 line of NAH: RADIANT, an international phase 4, randomized, open-label study – Trial in Progress (TiP)

    • Abstract TPS5093; June 4, 9:00am EDT
  • Abstract title: A phase III trial of docetaxel versus docetaxel and radium-223 (Ra-223) in patients with metastatic castration-resistant prostate cancer (mCRPC): DORA – Investigator-Initiated Research (IIR); Trial in Progress (TiP)

    • Abstract TPS5091; June 4, 9:00am EDT
  • Abstract title: A randomized trial of radium-223 dichloride and cabozantinib in patients (pts) with advanced renal cell carcinoma (RCC) with bone metastases (RADICAL/Alliance A031801) – Investigator-Initiated Research (IIR); Trial in Progress (TiP)

    • Abstract TPS4593; June 4, 9:00am EDT

Copanlisib

  • Abstract title: Copanlisib + rituximab versus rituximab + placebo in patients with relapsed follicular (FL) or marginal zone lymphoma (MZL): Subset analysis from the phase III CHRONOS-3 trial

    • Abstract 7510; June 4, 9:00am EDT

Regorafenib

  • Abstract title: Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC)

    • Abstract 4078; June 4, 9:00am EDT
  • Abstract title: Single-arm, phase 2 study of regorafenib plus nivolumab in patients with mismatch repair-proficient (pMMR)/microsatellite stable (MSS) colorectal cancer (CRC)

    • Abstract 3560; June 4, 9:00am EDT

Sorafenib

  • Abstract title: Genetic predictor of severe sorafenib-induced diarrhea and hand-foot syndrome (HFS)

    • Abstract 3030; June 4, 9:00am EDT

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%). 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%) 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%), 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 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 A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.

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) Injection5

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 in

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