For Immediate Release

Bayer Data at AACR 2019 Underscores Company's Commitment to Advancing the Future of Cancer Care

- Includes oral presentation on data from ongoing Phase I study with BAY 2731954 (formerly LOXO-195), a tropomyosin receptor kinase (TRK) inhibitor that is currently being investigated in patients who have progressed or were intolerant to prior TRK inhibitors

- Bayer is committed to expanding its precision oncology portfolio by bringing additional projects in this field forward

- A total of 30 presentations on promising projects across key areas of investigation: Oncogenic Signaling, Alpha Therapies and Immuno-Oncology

Abstracts: Oral presentations 924, CT127, 4454; Poster presentations: LB-075, 2, 228, 272, 1026, 1141, 1288, 2182, 2814, 3055, 3080, 3190, 3597, 3599, 3726, 3926, 3927, 3936, 3937, 3985, 4793, 4816, 4825, 4828, 4829, 5210, CT015

WHIPPANY, N.J., March 27, 2019 /PRNewswire/ -- Bayer will present research from its growing oncology portfolio at the American Association for Cancer Research (AACR) 2019 Annual Meeting, taking place March 29 to April 3 in Atlanta. The presentations highlight new findings on the company's key areas of investigation: Oncogenic Signaling, Alpha Therapies and Immuno-Oncology (IO). With a total of 30 presentations, including three oral presentations, the research underscores Bayer's commitment in oncology to advancing projects, many of which have the potential to be the first in class and address the underlying cause of cancer growth and spread. Bayer has two promising compounds in its precision oncology portfolio and is committed to expanding this portfolio. 

(PRNewsfoto/Bayer)

Among the data presented will be an oral presentation on the Phase I and expanded access experience of BAY 2731954 (formerly LOXO-195), an oral investigational TRK inhibitor. BAY 2731954 is currently in Phase I clinical development and designed for patients with cancers that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion and have progressed or were intolerant to prior TRK inhibitors. NTRK gene fusions are genomic alterations resulting in constitutively-activated tropomyosin receptor kinase (TRK) fusion proteins, which may lead to tumor growth.

In February 2019, Bayer announced that the company would obtain the exclusive licensing rights for the global development and commercialization, including in the U.S., for Vitrakvi® (larotrectinib) and BAY 2731954. Vitrakvi was approved by the U.S. FDA in November 2018. The option was triggered by the acquisition of Loxo Oncology by Eli Lilly and Company.

In another oral presentation, new pre-clinical data on the investigational androgen receptor (AR) antagonist darolutamide will be presented. Bayer recently submitted darolutamide for approval in the U.S., EU and Japan based on the data from the Phase III ARAMIS study, which investigated darolutamide in non-metastatic castration-resistant prostate cancer. At AACR, new findings will be presented on the pre-clinical data of darolutamide in different prostate cancer models in monotherapy and in combination with Bayer's investigational ataxia telangiectasia mutated and rad3-related kinase (ATR) inhibitor BAY 1895344. Darolutamide is being developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

In the area of IO, Bayer will present data on an oral investigational aryl hydrocarbon receptor (AhR) inhibitor as a therapeutic approach to enhance anti-tumoral immune responses. The AhR inhibitor was discovered and is being developed in collaboration with the German Cancer Research Center (DKFZ, Heidelberg, Germany).

Additional research to be presented includes pre-clinical data on the following investigational agents:

  • Rogaratinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor currently in Phase II/III clinical development is being investigated for urothelial carcinoma and other FGFR-positive tumors.
  • The dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234, derived from the collaboration with the Broad Institute (Cambridge, Massachusetts), that is currently in Phase I clinical trials in patients with acute myeloid leukemia. Research presented includes pre-clinical investigations in colorectal cancer and lymphoma.
  • The ATR inhibitor BAY 1895344, a DNA damage response inhibitor currently in Phase I clinical trials.
  • In the area of IO, the CEACAM6 function blocking antibody currently investigated in Phase I clinical trials, which was derived from Bayer's strategic collaboration with the DKFZ.
  • Bayer's emerging Targeted Thorium Conjugate (TTC) platform (a form of antibody Targeted Alpha Therapy). Research presented includes data on BAY 2315497, a TTC targeting the prostate-specific membrane antigen (PSMA), and BAY 2287411, the mesothelin-targeting TTC. Both development candidates are currently in Phase I clinical trials.
  • Anetumab ravtansine, a mesothelin targeting antibody-drug conjugate. Research presented includes data on anetumab ravtansine as monotherapy in non-small cell lung cancer (NSCLC) pre-clinical models.

Following is a list of oral and poster presentations at AACR 2019:

Oral presentations:

  • The androgen receptor antagonist darolutamide shows strong anti-tumor efficacy in patient- and cell line-derived xenograft prostate cancer models
    • Oral presentation 924, Session: MS.EN01.01 - Endocrine-Related Cancer Research
    • Sunday, March 31, 4:20 PM4:35 PM (EDT), Room C302 – Georgia World CC
  • Phase I and expanded access experience of LOXO-195 (BAY 2731954), a TRK inhibitor (TRKi)
    • Oral presentation CT127, Session: CTMS02 - The Next Generation of Clinical Trials in Molecularly-driven Therapy
    • Monday, April 1, 3:05 PM3:20 PM (EDT), Marcus Auditorium, Building A – Georgia World CC
  • Identification of BAY-218, a small molecule AhR inhibitor, as a modality to counteract tumor immunosuppression
    • Oral presentation 4454, Session: MS.CH01.01 - Next-Generation Small Molecules: From Hits to Leads to Candidates
    • Tuesday, April 2, 3:50 PM4:05 PM (EDT), Room B206 – Georgia World CC

Poster presentations:

  • Discovery of BAY 2402234 by phenotypic screening: A human Dihydroorotate Dehydrogenase (DHODH) inhibitor in clinical trials for the treatment of myeloid malignancies
    • Poster presentation 2, Session: PO.CH01.01 - Novel Small Molecules for Cancer Therapy
    • Sunday, March 31, 1:00 PM5:00 PM (EDT), Section 1
  • Synergistic activity of the ATR Inhibitor BAY1895344 in combination with immune checkpoint inhibitors in preclinical tumor models
    • Poster presentation 272, Session: PO.ET04.01 - Cell Death and DNA Repair Pathways
    • Sunday, March 31, 1:00 PM5:00 PM (EDT), Section 11
  • Preclinical analysis of biodistribution and PET imaging of a zirconium-89 labeled PSMA-targeted antibody-chelator-conjugate
    • Poster presentation 1141, Session: PO.TB07.01 - Novel Imaging Targets
    • Monday, April 1, 8:00 AM12:00 PM (EDT), Section 7
  • Increased T cell- activation resulting from the combination of the anti-CEACAM6 function-blocking antibody BAY 1834942 with checkpoint inhibitors targeting either PD-1/PD-L1 or TIM-3
    • Poster presentation LB-075, Session: LBPO.IM01 - Late-Breaking Research: Immunology 1
    • Monday, April 1, 8:00 AM12:00 PM (EDT), Section 41
  • Activity of pan-FGFR inhibitor rogaratinib and PI3K inhibitor copanlisib in preclinical urothelial bladder cancer models
    • Poster presentation 3080, Session: PO.ET06.03 - Novel Antitumor Agents 1
    • Tuesday, April 2, 8:00 AM12:00 PM (EDT), Section 14
  • BAY 2402234: Preclinical evaluation of dihydroorotate dehydrogenase (DHODH) inhibitor for the treatment of diffuse large B-cell lymphoma (DLBCL)
    • Poster presentation 3597, Session: PO.MCB08.04 - Targeting Metabolism for Cancer Therapy
    • Tuesday, April 2, 8:00 AM12:00 PM (EDT), Section 39
  • BAY 2402234: Preclinical evaluation of dihydroorotate dehydrogenase (DHODH) inhibitor for the treatment of colorectal carcinomas
    • Poster presentation 3599, Session: PO.MCB08.04 - Targeting Metabolism for Cancer Therapy
    • Tuesday, April 2, 8:00 AM12:00 PM (EDT), Section 39
  • Preclinical activity of PSMA-Targeted Thorium Conjugate (BAY 2315497) in combination with androgen receptor antagonists in prostate cancer models
    • Poster presentation 3726, Session: PO.TB09.02 - Radiation Tissue Tolerance, Immunity, and in Vivo Effects of Radiation
    • Tuesday, April 2, 1:00 PM5:00 PM (EDT), Section 5
  • MSLN-TTC (BAY 2287411) induces immunogenic cell death and secretion of pro-inflammatory cytokines in vitro and triggers an immune memory effect against a mouse tumor model
    • Poster presentation 3926, Session: PO.ET09.01 - Preclinical Radiotherapeutics
    • Tuesday, April 2, 1:00 PM5:00 PM (EDT), Section 15
  • Radium-223 α-particle radiation: Characterization of the in vitro effects on cancer cells in monotherapy and in combination with DNA repair inhibitors
    • Poster presentation 3927, Session: PO.ET09.01 - Preclinical Radiotherapeutics
    • Tuesday, April 2, 1:00 PM5:00 PM (EDT), Section 15
  • Efficacy of single agent radium-223 in the syngeneic MBT-2 bladder cancer bone growth model in mice
    • Poster presentation 3936, Session: PO.ET09.01 - Preclinical Radiotherapeutics
    • Tuesday, April 2, 1:00 PM5:00 PM (EDT), Section 15
  • MSLN-TTC (BAY 2287411) demonstrates increased activity in comparison to standard of care chemotherapy in models of acquired drug resistance
    • Poster presentation 3937, Session: PO.ET09.01 - Preclinical Radiotherapeutics
    • Tuesday, April 2, 1:00 PM5:00 PM (EDT), Section 15
  • Preclinical evaluation of the combination rogaratinib and copanlisib in HNSCC and HCC in preclinical in vitro and in vivo models
    • Poster presentation 4793, Session: PO.ET06.05 - Novel Antitumor Agents 3
    • Wednesday, April 3, 8:00 AM12:00 PM (EDT), Section 13
  • Anetumab ravtansine has monotherapy efficacy in mesothelin positive patient-derived NSCLC tumor models and in a syngeneic tumor model in immunocompetent mice
    • Poster presentation 4816, Session: PO.ET07.01 - Targeted Therapies
    • Wednesday, April 3, 8:00 AM12:00 PM (EDT), Section 14
  • Darolutamide impairs prostate cancer growth by altering chromatin conformation and transcriptional activity of genes involved in cell proliferation and survival
    • Poster presentation 520, Session: PO.MCB04.01 - Mechanisms and Consequences of Transcriptional Deregulation
    • Wednesday, April 3, 8:00 AM12:00 PM (EDT), Section 36

About Vitrakvi® (larotrectinib)
Vitrakvi® 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 that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments that have progressed following treatment.1 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. Research suggests that the NTRK genes can become abnormally fused to other genes, producing a TRK fusion protein that can act as an oncogenic driver, leading to cancer cell growth and survival.1

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 neurological 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%).1

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.1

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.1

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.1

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.1

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.1

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%).1 

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.1

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.1

Please see the full Prescribing Information for VITRAKVI® (larotrectinib).

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
Contraindications: Xofigo® is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman

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

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 Aliqopa (copanlisib) Injection3
Aliqopa (copanlisib) is indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Aliqopa has been shown to induce tumor cell death by apoptosis and inhibition of proliferation of primary malignant B cell lines. Aliqopa inhibits several key cell-signaling pathways, including B-cell receptor signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines.

The broad clinical development program for copanlisib also includes ongoing Phase III studies in indolent NHL (iNHL) patients who have relapsed or are refractory to prior therapies. The CHRONOS-3 Phase III study is evaluating copanlisib in combination with rituximab in relapsed iNHL and the CHRONOS-4 Phase III study is evaluating copanlisib in combination with standard immunochemotherapy in relapsed iNHL. More information about these trials can be found at www.clinicaltrials.gov.

Important Safety Information for Aliqopa (copanlisib) Injection

Infections: Serious, including fatal, infections occurred in 19% of 317 patients treated with ALIQOPA monotherapy. The most common serious infection was pneumonia. Monitor patients for signs and symptoms of infection and withhold ALIQOPA for Grade 3 and higher infection.

Serious pneumocystis jiroveci pneumonia (PJP) infection occurred in 0.6% of 317 patients treated with ALIQOPA monotherapy. Before initiating treatment with ALIQOPA, consider PJP prophylaxis for populations at risk.  Withhold ALIQOPA in patients with suspected PJP infection of any grade. If confirmed, treat infection until resolution, then resume ALIQOPA at previous dose with concomitant PJP prophylaxis.

Hyperglycemia: Grade 3 or 4 hyperglycemia (blood glucose 250 mg/dL or greater) occurred in 41% of 317 patients treated with ALIQOPA monotherapy. Serious hyperglycemic events occurred in 2.8% of patients. Treatment with ALIQOPA may result in infusion-related hyperglycemia. Blood glucose levels typically peaked 5 to 8 hours post-infusion and subsequently declined to baseline levels for a majority of patients; blood glucose levels remained elevated in 17.7% of patients one day after ALIQOPA infusion. Of 155 patients with baseline HbA1c <5.7%, 16 (10%) patients had HbA1c >6.5% at the end of treatment.

Of the twenty patients with diabetes mellitus treated in CHRONOS-1, seven developed Grade 4 hyperglycemia and two discontinued treatment. Patients with diabetes mellitus should only be treated with ALIQOPA following adequate glucose control and should be monitored closely. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hyperglycemia.

Achieve optimal blood glucose control before starting each ALIQOPA infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hyperglycemia.

Hypertension: Grade 3 hypertension (systolic 160 mmHg or greater or diastolic 100 mmHg or greater) occurred in 26% of 317 patients treated with ALIQOPA monotherapy. Serious hypertensive events occurred in 0.9% of 317 patients. Treatment with ALIQOPA may result in infusion-related hypertension. The mean change of systolic and diastolic BP from baseline to 2 hours post-infusion on Cycle 1 Day 1 was 16.8 mmHg and 7.8 mmHg, respectively. The mean BP started decreasing approximately 2 hours post-infusion; BP remained elevated for 6 to 8 hours after the start of the ALIQOPA infusion. Optimal BP control should be achieved before starting each ALIQOPA infusion. Monitor BP pre- and post-infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hypertension.

Non-infectious Pneumonitis: Non-infectious pneumonitis occurred in 5% of 317 patients treated with ALIQOPA monotherapy. Withhold ALIQOPA and conduct a diagnostic examination of a patient who is experiencing pulmonary symptoms such as cough, dyspnea, hypoxia, or interstitial infiltrates on radiologic exam. Patients with pneumonitis thought to be caused by ALIQOPA have been managed by withholding ALIQOPA and administration of systemic corticosteroids. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of non-infectious pneumonitis.

Neutropenia: Grade 3 or 4 neutropenia occurred in 24% of 317 patients treated with ALIQOPA monotherapy. Serious neutropenic events occurred in 1.3%. Monitor blood counts at least weekly during treatment with ALIQOPA. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of neutropenia.

Severe Cutaneous Reaction: Grade 3 and 4 cutaneous reactions occurred in 2.8% and 0.6% of 317 patients treated with ALIQOPA monotherapy respectively. Serious cutaneous reaction events were reported in 0.9%. The reported events included dermatitis exfoliative, exfoliative rash, pruritus, and rash (including maculo-papular rash). Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of severe cutaneous reactions.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ALIQOPA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of copanlisib to pregnant rats during organogenesis caused embryo-fetal death and fetal abnormalities in rats at maternal doses as low as 0.75 mg/kg/day (4.5 mg/m2/day body surface area) corresponding to approximately 12% the recommended dose for patients. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least one month after the last dose.

Adverse Drug Reactions: Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and hyperglycemia (5%). Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most frequently observed adverse drug reactions (≥20%) in ALIQOPA-treated patients were: hyperglycemia (54%), leukopenia (36%), diarrhea (36%), decreased general strength and energy (36%), hypertension (35%), neutropenia (32%), nausea (26%), thrombocytopenia (22%), and lower respiratory tract infections (21%).

Drug Interactions: Avoid concomitant use with strong CYP3A inducers. Reduce the ALIQOPA dose to 45 mg when concomitantly administered with strong CYP3A inhibitors.

Lactation: Advise women not to breastfeed. Advise a lactating woman not to breastfeed during treatment with ALIQOPA and for at least 1 month after the last dose.

Please see the full Prescribing Information of Aliqopa (copanlisib) Injection.

About Bayer's Research Platforms
Bayer focuses its research activities on first-in-class innovations across the following scientific platforms: Oncogenic Signaling, Alpha Therapies, and Immuno-Oncology. In the field of Oncogenic Signaling the company is developing small molecules and new modalities to target crucial pathways of intracellular tumor signaling that are responsible for the development and survival of cancer in well-defined patient populations (biomarker strategy). In regard to Targeted Alpha Therapies drug candidates are being developed using the company's proprietary Thorium-227 platform for delivering high-energy alpha-radiation via different targeting molecules such as antibodies to tumor cells. In Immuno-Oncology Bayer is developing next-generation agents that intervene at different levels of the cancer immune cycle specifically addressing the needs of patients not responding to current immunotherapies.

About BAY 2731954
BAY 2731954 is an oral investigational new drug in clinical development rationally designed for the treatment of patients with cancers that have progressed or were intolerant to prior TRK inhibitors. In July 2017, a multi-center Phase I/II trial in patients with TRK fusion cancers who have progressed while receiving another TRK inhibitor or are intolerant to another TRK inhibitor was initiated.

BAY 2731954 is not approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency or any other health authority.  

About darolutamide
Darolutamide is an investigational, non-steroidal androgen receptor antagonist in Phase III clinical trials for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). A Phase 3 study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about these trials can be found at www.clinicaltrials.gov.

Darolutamide is not approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency or any other health authority.

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 five 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 benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to www.bayer.us.

© 2019 Bayer
BAYER, the Bayer Cross, Vitrakvi, Aliqopa and Xofigo are registered trademarks of Bayer.

Media Contact:
Rose Talarico, Tel. +1 862.404.5302
E-Mail: rose.talarico@bayer.com

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.

Vitrakvi® (larotrectinib) capsules and solution for oral use [Prescribing Information]. Stamford, CT: Loxo Oncology Inc.; November 2018.


2.

XOFIGO® (radium-223 dichloride) Injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, February 2018.


3.

Aliqopa™ (copanlisib) for injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, September 2017.

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SOURCE Bayer