Bayer to Present Data from Growing Oncology Portfolio at the ASCO20 Virtual Scientific Program

• Data on final analysis of overall survival (OS) from the Phase III ARAMIS trial investigating NUBEQA^® (darolutamide) in men with non-metastatic castration-resistant prostate cancer (nmCRPC)
• Updated efficacy and safety data for Vitrakvi^® (larotrectinib) from an expanded set of adult patients with TRK fusion cancer and a quality of life (QoL) analysis in adult and pediatric patients
• New safety and efficacy data from established compounds including Xofigo^® (radium Ra 223 dichloride) and Stivarga^® (regorafenib) 

Abstracts: 5514, 5561, TPS5593, TPS5587, 5551, 3610, 3614, TPS10560, 5542, TPS5594, TPS5586, 5540, 5565, 4019, 10507, 3593, TPS4114, 3506

WHIPPANY, N.J.–(BUSINESS WIRE)–Data from Bayer’s growing oncology portfolio will be presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program, taking place from May 29-31, 2020. Presentations will feature data across approved products, exploring therapies across different tumor types and treatment settings. Information on the registration as well as the virtual scientific program can be found here.

Data on the final analysis of overall survival (OS) from the Phase III ARAMIS trial investigating NUBEQA^® (darolutamide) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) will be presented in a virtual poster discussion on May 29, 2020. In January, it was announced results showed a significant improvement in OS in patients receiving darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT. A separate analysis on safety outcomes between darolutamide, apalutamide and enzalutamide using matching-adjusted indirect comparison (MAIC), a method to perform indirect treatment comparisons adjusting for cross-trial heterogeneity, will also be presented. NUBEQA, an oral androgen receptor inhibitor (ARi), has been approved in the U.S., Brazil, Japan and the European Union (EU), and filings in other regions are underway or planned. The compound is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

Updated efficacy and safety data for Vitrakvi^® (larotrectinib) from an expanded set of adult patients with TRK fusion cancer and a quality of life (QoL) analysis in adult and pediatric patients treated with larotrectinib will be presented at the meeting. Vitrakvi is approved in the U.S., Canada, Brazil and the EU. Vitrakvi is approved in the U.S. 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 is likely to result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Additional filings in other regions are underway or planned.

Xofigo^® (radium Ra 223 dichloride) data include results from a Phase II trial investigating Xofigo and niraparib in metastatic castration-resistant prostate cancer (mCRPC) with and without prior chemotherapy and a second interim analysis from the REASSURE trial evaluating safety and OS in mCRPC patients. Additionally, the trial design of a Phase III collaboration study (DORA) investigating docetaxel versus docetaxel and Xofigo will be presented.

Data on Stivarga^® (regorafenib) include an oral presentation for an investigator-initiated Phase I study of Stivarga in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumors, as well as preliminary results of an investigator-initiated Phase II trial (REGOMUNE) evaluating Stivarga plus avelumab, an immune checkpoint inhibitor, in a certain colorectal cancer (CRC) cohort.

Notable presentations at the ASCO Virtual Scientific Program are listed below and will be available online beginning May 29, 2020 at 8:00 AM ET:

Darolutamide

• Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for non-metastatic castration-resistant prostate cancer (nmCRPC)
  • Abstract: 5514, Genitourinary Cancer—Prostate, Testicular, and Penile
• Safety outcomes of darolutamide versus apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer (nmCRPC): Matching-adjusted indirect comparisons
  • Abstract: 5561, Genitourinary Cancer—Prostate, Testicular, and Penile
• DAROL: DARolutamide ObservationaL study patients in non-metastatic castration-resistant prostate cancer (nmCRPC) patients – Trial in Progress
  • Abstract: TPS5593, Genitourinary Cancer—Prostate, Testicular, and Penile
• DaroACT: Darolutamide and enzalutamide effects on physical and neurocognitive function and daily activity in patients with castration-resistant prostate cancer (CRPC) – Trial in Progress
  • Abstract: TPS5587, Genitourinary Cancer—Prostate, Testicular, and Penile
• Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) study: A Canadian Cancer Trials group phase II umbrella trial for metastatic castration-resistant prostate cancer (mCRPC) – Investigator-initiated research
  • Abstract: 5551, Genitourinary Cancer—Prostate, Testicular, and Penile

Larotrectinib

• Activity and safety of larotrectinib in adult patients with TRK fusion cancer: An expanded data set
  • Abstract: 3610, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
• Quality of life of adults and children with TRK fusion cancer treated with larotrectinib compared to the general population
  • Abstract: 3614, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
• A phase II study of larotrectinib for children with newly diagnosed solid tumors and relapsed acute leukemias harboring TRK fusions: Children’s Oncology Group study ADVL1823 – Trial in Progress; Investigator-initiated research
  • Abstract: TPS10560, Pediatric Oncology

Radium-223 dichloride (Ra-223)

• Safety and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) plus subsequent taxane therapy
  • Abstract: 5542, Genitourinary Cancer—Prostate, Testicular, and Penile
• A phase III trial of docetaxel versus docetaxel and radium-223 (Ra-223) in patients with metastatic castration-resistant prostate cancer (mCRPC): DORA – Trial in Progress
  • Abstract: TPS5594, Genitourinary Cancer—Prostate, Testicular, and Penile
• A phase II randomized trial of RAdium-223 dichloride and SABR versus SABR for oligomEtastatic prostate caNcerS (RAVENS) – Trial in Progress; Investigator-initiated research
  • Abstract: TPS5586, Genitourinary Cancer—Prostate, Testicular, and Penile
• Radium-223 (Rad) and niraparib (Nira) treatment (tx) in castrate resistant prostate cancer (CRPC) patients (pts) with and without prior chemotherapy (chemo) – Investigator-initiated research
  • Abstract: 5540, Genitourinary Cancer—Prostate, Testicular, and Penile
• Safety and clinical activity of atezolizumab (atezo) + radium-223 dichloride (r-223) in 2L metastatic castration-resistant prostate cancer (mCRPC): Results from a phase Ib clinical trial
  • Abstract: 5565, Genitourinary Cancer—Prostate, Testicular, and Penile

Regorafenib

• REGOMUNE: A phase II study of regorafenib plus avelumab in solid tumors, results of the non-MSI-H metastatic colorectal cancer (mCRC) cohort – Investigator-initiated research
  • Abstract: 4019, Gastrointestinal Cancer—Colorectal and Anal
• Phase I study of regorafenib in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumors
  • Abstract: 10507, Pediatric Oncology
• Phase I study of regorafenib and sildenafil in advanced solid tumors – Investigator-initiated research
  • Abstract: 3593, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Copanlisib

• A phase I/II study of PI3Kinase inhibition with copanlisib combined with the anti-PD-1 antibody nivolumab in relapsed/ refractory solid tumors with expansions in MSS colorectal cancer – Investigator-initiated research
  • Abstract: TPS4114, Gastrointestinal Cancer—Colorectal and Anal
• Phase II study of copanlisib in patients with tumors with PIK3CA mutations (PTEN loss allowed): NCI MATCH EAY131-Z1F – Investigator-initiated research
  • Abstract: 3506, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

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.

On July 30th, 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 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 or placebo plus ADT. The primary efficacy endpoint was MFS, defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death due to any cause within 33 weeks after the last evaluable scan, whichever occurred first. NUBEQA plus ADT demonstrated a statistically significant improvement in MFS, with a median MFS of 40.4 months [95% CI (34.3, NR), p<0.0001] versus 18.4 months [95% CI (15.5, 22.3), p<0.0001] with placebo plus ADT [HR=0.41, 95% CI (0.34, 0.50), p<0.0001].

Adverse reactions occurring more frequently in the NUBEQA arm (≥2 % over placebo) were fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% versus 1%). NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.

INDICATION for NUBEQA (darolutamide)

NUBEQA is approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).¹

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

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%).

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.

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 –Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers.

Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure, which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed.

Effects of NUBEQA on Other Drugs –NUBEQA is an inhibitor of breast cancer resistance protein (BCRP) transporter. Concomitant use of NUBEQA increases the exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. Consult the approved product labeling of the BCRP substrate when used concomitantly with NUBEQA.

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

About VITRAKVI^® (larotrectinib)²

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, 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.

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%).

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.

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.

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%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).

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 Xofigo^® (radium Ra 223 dichloride) Injection³

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).

Contacts

Rose Talarico, Tel. +1 862.404.5302

E-Mail: [email protected]

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