On September 9, 2020 AskAt reported that it received a Notice of Allowance issued on August 17, 2020 from the Mexican Patent and Trademark Office (MPTO) in connection with Application No.MX/a/2018/005715, a use patent for AskAt’s EP4 receptor antagonists in the treatment of NASH-associated liver cancer (Press release, AskAt, SEP 9, 2020, View Source [SID1234564827]).

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On September 9, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it will present new research data for patritumab deruxtecan (U3-1402) and ENHERTU (fam-trastuzumab deruxtecan-nxki), two of its lead DXd antibody drug conjugates (ADC), at the 2020 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Scientific Program to be held September 19-21, 2020 (#ESMO20) (Press release, Daiichi Sankyo, SEP 9, 2020, https://www.businesswire.com/news/home/20200909005025/en/Late-Breaking-Data-Daiichi-Sankyo%E2%80%99s-HER3-Directed-ADC [SID1234564847]).

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The late-breaking presentation of patritumab deruxtecan, a potential first-in-class HER3 directed ADC, will feature an analysis that includes the first safety and efficacy results from the dose expansion cohort of a phase 1 clinical trial in patients with EGFR mutated unresectable advanced non-small cell lung cancer (NSCLC) previously treated with a tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Data from the HER2 low expression exploratory cohorts of the pivotal phase 2 DESTINY-Gastric01 study of ENHERTU in patients with previously treated advanced gastric or gastroesophageal junction cancer will also be presented.

"We look forward to presenting these new results from the ongoing phase 1 study of patritumab deruxtecan in patients with previously treated, advanced EGFR mutated NSCLC, which reflect encouraging progress in the clinical development of this HER3 directed therapy," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "These data, along with the current body of research across our ADC portfolio, demonstrate significant progress in our oncology pipeline and underscore our commitment to translating our DXd ADC technology into potential new treatment options for patients across a number of tumor types."

Following is an overview of the research data from the oncology portfolio of Daiichi Sankyo to be presented at ESMO (Free ESMO Whitepaper) 2020:

ESMO Virtual Scientific Program Abstract Title

Presentation Details

PATRITUMAB DERUXTECAN (HER3 ADC)

Efficacy and safety of patritumab deruxtecan (U3-1402), a novel HER3 directed antibody drug conjugate, in patients with EGFR-mutated (EGFRm) NSCLC

Late-Breaker Mini-Oral Presentation (#LBA62): H Yu, et al.; September 18, 2020 at 9:00 a.m. CEST

ENHERTU (HER2 ADC)

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2 low, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: results of the exploratory cohorts in the phase 2, multicenter, open-label DESTINY-Gastric01 study

Mini-Oral Presentation (#1422MO): Yamaguchi, et al. Gastrointestinal tumors, non-colorectal; September 18, 2020 at 9:00 a.m. CEST

A phase 1b/2, multicenter, open-label, dose-escalation and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd; DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03) [TiP]

E-poster Presentation (#1500TiP): Janjigian, et al.; September 17, 2020 at 9:00 a.m. CEST

Patient preferences for HER2-targeted treatment of advanced or metastatic breast cancer in the United States

E-poster Presentation (#340P): Mansfield, et al.; September 17, 2020 at 9:00 a.m. CEST

Risk factors for interstitial lung disease in patients treated with trastuzumab deruxtecan from two interventional studies

E-poster Presentation (#289P): Powell, et al.; September 17, 2020 at 9:00 a.m. CEST

Artificial intelligence analysis of advanced breast cancer patients from a phase 1 trial of trastuzumab deruxtecan (T-DXd): HER2 and histopathology features as predictors of clinical benefit

E-poster Presentation (#286P): Modi, et al.; September 17, 2020 at 9:00 a.m. CEST

About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of seven antibody drug conjugates (ADCs) with five in clinical development across multiple types of cancer. These include ENHERTU, a HER2 directed ADC, and DS-1062, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca; patritumab deruxtecan (U3-1402), a HER3 directed ADC; and DS-7300, a B7-H3 directed ADC, and DS-6157, a GPR20 directed ADC, which are being developed through a strategic research collaboration with Sarah Cannon Cancer Institute.

Each ADC is engineered using Daiichi Sankyo’s proprietary and portable DXd ADC technology to target and deliver chemotherapy inside cancer cells that express a specific cell surface antigen. Each ADC consists of a monoclonal antibody attached by a stable tetrapeptide-based linker to a topoisomerase I inhibitor payload (chemotherapy) with a customized drug to antibody ratio (DAR) to optimize the risk-benefit ratio for the intended patient population.

ENHERTU (5.4 mg/kg) is approved in the U.S. and Japan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial. ENHERTU has not been approved in the EU, or countries outside of the U.S. and Japan for any indication. It is an investigational agent globally for various indications. Safety and effectiveness have not been established for the proposed uses being investigated in ongoing studies. Patritumab deruxtecan (U3-1402) is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

U.S. FDA-Approved Indication for ENHERTU
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Contraindications
None.

WARNINGS AND PRECAUTIONS

Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg prednisolone or equivalent). Upon improvement, follow by gradual taper (e.g., 4 weeks).

Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, a decrease in neutrophil count was reported in 30% of patients and 16% had Grade 3 or 4 events. Median time to first onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was reported in 1.7% of patients.

Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of >20% is confirmed. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Adverse Reactions
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia (20%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%).
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNING, and Medication Guide.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

On September 9, 2020 Bausch Health Companies Inc. (NYSE/TSX: BHC) reported that Joseph C. Papa, chairman and CEO; Sam Eldessouky, senior vice president and corporate controller; and Arthur J. Shannon, senior vice president and head of Investor Relations and Communications, are scheduled to participate at the virtual 18th Annual Morgan Stanley Global Healthcare Conference on Sept. 16, 2020 at 1:15 p.m. ET (Press release, Bausch Health, SEP 9, 2020, View Source [SID1234564883]).

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A live webcast and audio archive of the events will be available on the Investor Relations page of the Bausch Health Companies Inc. web site at: View Source

On September 9, 2020 Haemonetics Corporation (NYSE: HAE) reported that Chris Simon, President and CEO, will present at the 18th Annual Morgan Stanley Virtual Global Healthcare Conference on Tuesday, Sept. 15, 2020, at 9:30 a.m. ET (Press release, Haemonetics, SEP 9, 2020, View Source [SID1234564908]).

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The public may access Mr. Simon’s presentation live via webcast and subsequent replay at: View Source;tp_key=8d479de3b1

On September 9, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that six e-posters highlighting clinical data from the lucitanib and Rubraca (rucaparib) clinical development programs, as well as preclinical data for FAP-2286, will be presented at the ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) Virtual Congress 2020, September 19 – September 21, 2020 (Press release, Clovis Oncology, SEP 9, 2020, View Source [SID1234564806]).

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E-posters for presentation include the following:

Initial data from the Phase 1b part of the LIO-1 study in patients with an advanced metastatic solid tumor, which aimed to determine the recommended Phase 2 starting dose of lucitanib in combination with nivolumab and to provide safety, pharmacokinetic and preliminary efficacy data for the combination.
A Trials in Progress e-poster describing the design of the Phase 2 part of the LIO-1 study, which is now enrolling patients, and will evaluate the combination’s safety and efficacy in patients with an advanced gynecological solid tumor, including ovarian, endometrial and cervical cancers.
Analyses of pharmacokinetics and relationships between exposure and efficacy/safety in patients with metastatic castration-resistant prostate cancer (mCRPC) from the Phase 2 TRITON2 study of Rubraca, the primary analysis of which served as the pivotal data supporting FDA approval of Rubraca as the first poly-ADP ribose polymerase (PARP) inhibitor for patients with advanced mCRPC associated with a BRCA mutation.
New analysis of data from the Phase 3 ARIEL3 study evaluating the prevalence, timing, and duration of adverse events for Rubraca maintenance therapy in recurrent ovarian cancer.
Initial data from the Phase 1b part of the Phase 1b/2 SEASTAR study arm evaluating Rubraca in combination with sacituzumab govitecan for the treatment of metastatic solid tumors, which aims to evaluate the tolerability and preliminary efficacy for the combination.
The first presentation of preclinical data in
in vivo
and
in vitro
models for FAP-2286, a novel peptide-targeted radionucleotide therapy (PTRT) and imaging agent for which Clovis intends to file imaging and treatment Investigational New Drug applications to the FDA in late 2020.
"We have made significant progress in expanding the breadth and depth of our oncology development portfolio, including our pipeline compounds lucitanib and FAP-2286. We are excited to share new data and updates for all three compounds from our clinical and preclinical development programs at this year’s ESMO (Free ESMO Whitepaper) congress," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We remain committed to developing targeted therapies to better serve patients, and believe delivering the right drug to the right patient at the right time represents the future of cancer therapy."

The following abstracts will be available as e-posters for on-demand viewing on the ESMO (Free ESMO Whitepaper) website at 9:00 a.m. CEST on Thursday, September 17, 2020. The e-posters will also be available online at www.clovisoncology.com/pipeline/scientific-presentations once they are made available during the congress.

Lucitanib

E-poster Number 556P: Initial Clinical Experience of Lucitanib + Nivolumab in Advanced Metastatic Solid Tumours: Data From the Phase 1b/2 LIO-1 Study (CO-3810-101; NCT04042116)
Lead author: Dr. Erika Hamilton, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, United States of America

E-poster Number 885TiP: LIO-1: A Phase 2 Study of Lucitanib + Nivolumab in Patients (pts) With Gynecological Tumours (CO-3810-101; NCT04042116; ENGOT-GYN3/AGO/LIO)
Lead author: Prof. Nicole Concin, Kliniken Essen-Mitte, Essen, Germany, and Medizinische Universität Innsbruck, Austria

Rucaparib

E-poster Number 659P: Rucaparib Population Pharmacokinetics (PPK) and Exposure-Response (ER) Analyses in Patients (pts) With Metastatic Castration-Resistant Prostate Cancer (mCRPC) in TRITON2
Lead author: Dr. Simon Chowdhury, Guy’s Hospital, London and Sarah Cannon Research Institute, London, United Kingdom

E-poster Number 821P: Timing of Adverse Events During Maintenance Treatment With Rucaparib for Recurrent Ovarian Cancer in the Phase 3 ARIEL3 Study
Lead author: Dr. Andrew Dean, St John of God Subiaco Hospital, Subiaco, Australia

E-poster Number 547P: Rucaparib + Sacituzumab Govitecan (SG): Initial Data From the Phase 1b/2 SEASTAR Study (NCT03992131)
Lead author: Dr. Timothy A. Yap, The University of Texas MD Anderson Cancer Center, Houston, United States of America

FAP-2286

E-poster Number 571P: Preclinical Evaluation of FAP-2286, a Peptide-targeted Radionuclide Therapy (PTRT) to Fibroblast Activation Protein Alpha (FAP)
Lead author: Dr. Dirk Zboralski, 3B Pharmaceuticals GmbH, Berlin, Germany

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca is an unlicensed medical product outside of the U.S. and Europe.

Rubraca (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2 prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca, and are generally low grade (CTCAE grade 1 or 2), and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

Click here to access the current SPC. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

Rubraca U.S. FDA Approved Indications

Ovarian Cancer

Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated for the treatment of adult women with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

Prostate Cancer

Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca. For males on Rubraca treatment who have female partners of reproductive potential or who are pregnant, effective contraception should be used during treatment and for 3 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose.

Please click here for full Prescribing Information for Rubraca.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs may reverse this immunosuppression and augment response to immunotherapy.

Lucitanib is an unlicensed medical product.

About FAP-2286

FAP-2286 is a preclinical candidate discovered by 3B Pharmaceuticals under investigation as a PTRT and imaging agent targeting fibroblast activation protein alpha (FAP). FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis is planning to submit an investigational new drug application (IND) for FAP-2286 in the second half of 2020. Clovis will conduct the global clinical trials and holds U.S. and global rights, excluding Europe.

FAP-2286 is an unlicensed medical product.