On December 21, 2020 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported initial data from two clinical studies of galinpepimut-S (GPS), the Company’s Wilms Tumor-1 (WT1)-targeting peptide immunotherapeutic, in combination with checkpoint inhibitor therapies in patients with two different types of advanced solid cancers who had exhausted their standard therapy options (Press release, Sellas Life Sciences, DEC 21, 2020, View Source [SID1234573161]).

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In the first study, a phase 1/2 ‘basket’ trial of GPS in combination with the checkpoint inhibitor pembrolizumab (Keytruda), which is conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), the first set of evaluable patients (n = 8) diagnosed with 2nd or 3rd line WT1(+) relapsed or refractory metastatic ovarian cancer demonstrated a disease control rate (the sum of overall response rate and rate of stable disease) of 87.5% with a median follow-up of 9.4 weeks. In this difficult to treat patient population, at the first assessment time-point of 6 weeks post-therapy initiation, 100% of the patients were free of disease progression. Using a validated immunohistochemistry (IHC) assay during the screening period, the rate of WT1 positivity in this ovarian cancer patient population was approximately 70%. Six of the eight evaluable patients are continuing to receive GPS plus pembrolizumab. Enrollment is continuing with a target of a total of 20 patients. More mature clinical and immunobiological data are expected to be announced by the end of the second quarter of 2021.

In the second study, a Phase 1 investigator-sponsored clinical trial (IST) of GPS in combination with the checkpoint inhibitor nivolumab (Opdivo) in patients with macroscopic measurable deposits of malignant pleural mesothelioma (MPM) who were either refractory to or relapsed after frontline tri-modality standard therapy, the first set of evaluable patients (n = 3) had a median progression free survival of at least 10 weeks since therapy initiation. In primary refractory MPM patients, any prolongation of progression-free interval greater than 8 weeks would be considered clinically meaningful, considering the current lack of effective therapies. All patients had the epithelioid variant of MPM, a tumor which is universally expressing WT1. Moreover, in this study, GPS was found to be appropriately immunogenic, leading to the emergence of antigen (WT1)-specific CD4+ T-memory cell responses at 3 months post-therapy initiation. Additional MPM patients are currently being enrolled; completion of study enrollment (target total n = 10) and more mature clinical and immunobiological data are expected by the end of the second quarter of 2021.

In both studies, the safety profile of the combination of GPS with the checkpoint inhibitor was similar to that seen with checkpoint inhibitors alone, with the addition of only low grade, transitory local reactions at the site of injection of GPS, consistent with previously performed clinical studies of GPS.

"These early data confirm the tolerability profile seen in earlier studies of GPS, which is one of the primary endpoints in these solid cancer trials, in a variety of cancer indications, even in the most refractory patients who underwent numerous prior therapies," commented Jeffrey S. Weber, MD, PhD, Deputy Director of the Perlmutter Cancer Center at New York University (NYU)-Langone Health, co-Director of its Melanoma Research Program Center and Chair of SELLAS’ Scientific Advisory Board. "These safety findings are accompanied by promising early indications of an efficacy signal for patients with advanced metastatic disease, whose management is extremely challenging even with checkpoint inhibitor monotherapy."

"We are encouraged by the data shown in these two studies of GPS in combination with checkpoint inhibitors and look forward to additional data from these studies," stated Dragan Cicic, MD, Senior Vice President, Clinical Development of SELLAS. "We now have early evidence that supports further expanding the field of potential GPS indications into solid cancers with high rates of WT1 positivity. GPS has previously been shown to invoke multi-epitope, broad cross-reactivity along the full-length of the WT1 protein, suggestive of epitope spreading, and immunologically mediated cancer cell destruction, which are hallmarks of an effective cancer vaccine. The scientific rationale in combining GPS with checkpoint inhibitors is the immunbiologic and pharmacodynamic synergy between the two agents, whereby the negative influence of the tumor microenvironment is mitigated by checkpoint inhibitors and thus allowing the patients’ own immune cells specifically sensitized against WT1, by GPS, to invade and destroy cancerous cells."

About the Phase 1/2 Basket Study of GPS in Combination with Pembrolizumab (Keytruda) in Patients with Selected WT1-Positive Advanced Cancers, Including Ovarian Cancer

This is a Phase 1/2 open-label, multicenter, multi-arm study conducted under a Clinical Trial Collaboration and Supply Agreement (CTSA) with Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada) to assess the efficacy and safety of the combination of GPS and pembrolizumab (Keytruda) (ClinicalTrials.gov identifier: NCT03761914). The primary endpoints of the study include safety and overall response rate, while secondary endpoints include progression-free survival, overall survival and immune response correlates. The study will enroll approximately 90 patients at up to 20 centers in the United States. The trial is currently evaluating patients with ovarian cancer (second or third line).

About the Phase 1 Trial of GPS in Combination with Nivolumab (Opdivo) in Patients with Malignant Pleural Mesothelioma (MPM)

This is a Phase 1 open-label clinical study conducted by Memorial Sloan Kettering Cancer Center (MSK) and is enrolling patients with MPM who harbor relapsed or refractory disease after having received frontline, standard-of-care multimodality therapy (target total n = 10; ClinicalTrials.gov identifier: NCT04040231). The principal investigator for the study is Marjorie G. Zauderer, MD, Co-Director, Mesothelioma Program and Associate Attending Physician in the Thoracic Oncology Service, Department of Medicine at MSK. The trial is investigating the potential of GPS in combination with nivolumab (Opdivo) to demonstrate anti-tumor immune responses and meaningful clinical activity in the presence of macroscopic advanced disease in MPM patients and gauging the degree of clinical benefit by assessment of the overall response rate with the combination in comparison with that reported with nivolumab alone in historical comparable patient populations.

Keytruda is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA, and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products. Opdivo is a registered trademark of Bristol Myers Squibb, and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

On December 21, 2020 Propanc Biopharma, Inc. (OTC: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the first granted patent for an important patent family (i.e., a set of patents filed in various countries to protect an invention) was received by the Company from the Australian Patent Office (Press release, Propanc, DEC 21, 2020, View Source [SID1234573160]). The granted patent protects proprietary claims, capturing methods and uses for pancreatic proenzymes to treat cancer, specifically, by targeting and eradicating cancer stem cells ("CSCs"). CSCs represent only a small fraction of the cancer cells within a tumor and can remain dormant for extended periods of time, thereby evading standard treatments like chemotherapy and radiotherapy that target dividing cells. Consequently, a priority for improving cancer treatment and reducing risk of cancer relapse is to develop new strategies that selectively target CSC eradication whilst sparing normal stem cells. This continues to be the focus of ongoing research, as the Company’s lead product candidate, PRP, advances towards clinical trials for the treatment of patients with advanced solid tumors.

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The granted patent, citing the novel CSC treatment method, is one of our four patent families, consisting of 65 patents either in force, or pending, and is the first to be granted covering a method of minimizing the progression of cancer in a patient by administering a therapeutically effective amount of the two proenzymes, trypsinogen and chymotrypsinogen, thereby preventing metastatic, or spreading cancer in the patient. As a result, examination of patent applications in a number of other jurisdictions can be expedited where the Australian claims will be utilized for supplementary examination.

"The advancement of this patent to grant status in Australia is a significant step forward for our intellectual property portfolio and represents a novel therapeutic approach for the treatment and prevention of metastatic cancer by targeting and eradicating cancer stem cells, which is the main cause of death for sufferers," said James Nathanielsz, Propanc’s Chief Executive Officer. "It is especially important to continue to expand and grow our intellectual property portfolio as we advance PRP to clinical trials."

"Our main point of difference from other CSC therapies is the ability of our technology to differentiate cancer stem cells back towards normal cell behavior, so they die naturally, rather than directly killing CSCs. This way, we selectively target CSCs, leaving healthy stem cells alone, which means PRP is less toxic compared to standard treatment approaches," said Dr Julian Kenyon, Propanc’s Chief Scientific Officer. "Expanding our intellectual property portfolio by patenting new inventions using a world first, novel proenzyme treatment approach to target CSCs builds confidence that we are on track with our research."

On December 21, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported receipt of U.S. Food and Drug Administration (FDA) permission for a Phase 1 study to proceed under the Company’s Investigational New Drug application (IND) for ON 123300, a proprietary, differentiated, first-in-class multi-kinase inhibitor (Press release, Onconova, DEC 21, 2020, View Source [SID1234573159]).

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"We are grateful to receive this timely, favorable response from the FDA to initiate a Phase 1 trial with ON 123300," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "We are advancing the process to secure Institutional Review Board approval, and affirm our expectation that the first patient will be enrolled during the first half of 2021."

The Phase 1 trial will be conducted in the U.S. and will assess the safety, tolerability and pharmacokinetics of ON 123300 administered orally as monotherapy at increasing doses starting at 40 mg daily or higher for consecutive 28-day cycles. The trial will enroll patients with relapsed/refractory advanced cancer, including but not limited to patients with HR+ HER2- metastatic breast cancer with clinical resistance to approved second-generation CDK4/6 inhibitors. Once the dose escalation phase of the trial is completed and the recommended Phase 2 dose is established, additional HR+ HER2- postmenopausal metastatic breast cancer patients resistant to approved second-generation CDK4/6 inhibitors will be enrolled. Additional patient cohorts are under consideration, including but not limited to patients diagnosed with advanced colorectal cancer, and non-Hodgkin’s lymphoma, in particular mantle cell lymphoma.

The design of this U.S. Phase 1 trial differs from the ongoing study with ON 123300 in China conducted by the Company’s partner HanX Biopharmaceuticals, Inc., which is dosing patients daily for 21 days. The HanX trial has enrolled four patients to date, has opened the second dosing cohort and is expected to continue enrolling patients with advanced cancer at two sites until the recommended Phase 2 dose is identified. Notably, of the three currently approved CDK4/6 inhibitors, two are approved for dosing in 21-day cycles and one is approved for dosing in a 28-day cycle. All three are blockbuster drugs marketed in HR+ HER2– metastatic breast cancer by well-known pharmaceutical companies, and all of these approved therapies require concomitant treatment with an aromatase inhibitor.

"Based on its differentiated mechanism of action, we believe that ON 123300 presents an innovative approach to study advanced cancers including in HR+ HER2- metastatic breast cancer that is or has become resistant to commercial CDK4/6 inhibitors. Beyond metastatic breast cancer, we believe that ON 123300 may present a novel approach to treating other cancers including mantle cell lymphoma, multiple myeloma, advanced colorectal cancer and hepatocellular carcinoma, as well as inoperable glioblastoma based on preclinical studies suggesting ON 123300 crosses the blood-brain barrier," added Richard Woodman, M.D, Chief Medical Officer.

About ON 123300

Onconova’s lead pipeline compound is the novel small molecule ON 123300, a proprietary, first-in-class multi-kinase inhibitor targeting tumor-driving kinases including CDK4/6 and ARK5. ON 123300 is reported to simultaneously inhibit both cell cycle and cellular energy metabolism through CDK4/6 and ARK5, respectively, and in vitro has been shown to be cytotoxic to cancer cells (killing the cancer cells). The current commercial CDK inhibitors are reported to be cytostatic (inhibiting the growth of cancer cells). With its differentiated mechanism of action, ON 123300 may present an innovative approach for treating solid tumors and hematologic malignancies that are refractory to or have become resistant to other CDK4/6 inhibitors. Based on experiments in preclinical models, ON 123300 exhibits single-agent cytotoxicity, and may have utility for certain types of cancers including breast cancer, non-Hodgkin’s lymphoma including mantle cell lymphoma, multiple myeloma, colorectal cancer, hepatocellular carcinoma, and inoperable glioblastoma.

On December 21, 2020 Equillium, Inc. (Nasdaq: EQ) a clinical-stage biotechnology company developing itolizumab to treat severe autoimmune and inflammatory disorders, reported the appointment of Dolca Thomas, M.D., as its executive vice president of research and development and chief medical officer (Press release, Equillium, DEC 21, 2020, View Source [SID1234573158]). Dr. Thomas joins Equillium from Principia Biopharma (recently acquired by Sanofi) where she was chief medical officer focused on developing treatments for immune-mediated diseases.

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"Equillium has made tremendous progress in 2020 and is now at a critical juncture as we begin to strategically outline more advanced development of itolizumab," said Bruce Steel, chief executive officer at Equillium. "Dolca’s significant track record of success and broad experience in executing late-stage programs, specifically in immunology, comes to Equillium at an important time. With several key readouts expected over the next twelve months, as well as interactions with the U.S. Food and Drug Administration that will help guide the future of our lead program in acute graft versus host disease, her expertise will come to bear immediately. I’d also like to take this opportunity to thank Dr. Krishna Polu, our departing chief medical officer, who contributed significantly to advancing our clinical programs and building our experienced research and development team; we wish Krishna well as he transitions to a new role in venture capital."

"I’m thrilled to join Equillium at such an exciting time and to advance the development of itolizumab, a highly novel drug targeting the CD6-ALCAM co-stimulatory signaling pathway. Modulating this biology may potentially have therapeutic effect in a number of immuno-inflammatory diseases beyond the current pipeline," said Dr. Thomas. "I look forward to guiding itolizumab’s path to registration in acute graft versus host disease, leading our clinical research efforts in lupus/lupus nephritis and uncontrolled asthma, and building a pipeline where we can have the most profound effect on the lives of patients."

Dr. Thomas brings almost two decades of industry and medical experience with strategic and operational responsibility for clinical development, pharmacovigilance, safety and medical affairs of approximately two dozen pharmaceutical product candidates. Prior to her position as chief medical officer at Principia, Dr. Thomas was vice president and global head of translational medicine for immunology, inflammation, and infectious disease at Roche, where she was responsible for advancing multiple product candidates through clinical development. Prior to Roche, Dr. Thomas held roles of increasing responsibility at Pfizer, including vice president of clinical development and clinical immunophenotyping, and vice president and chief development officer of the biosimilars research and development unit where she was responsible for all stages of development of multiple assets. Dr. Thomas began her industry career at Bristol-Myers Squibb as director of global clinical development in immunology, where she was involved in the development and approval of belatacept, a novel therapeutic targeting the co-stimulatory pathway CD28.

Dr. Thomas received her medical degree from Cornell University and completed her residency in internal medicine, in addition to her post-doctoral training in nephrology and transplantation, at New York-Presbyterian Hospital, Weill Cornell Medical Center.

"Supporting the momentum we have achieved, we are continuing to build the company," continued Mr. Steel. "I am pleased to announce that we have recently added Michael Son, Ph.D., as vice president of regulatory affairs, Nelson Lugo as vice president of manufacturing, and Michael Moore as vice president of investor relations and corporate communications. Their leadership has already begun to pay dividends and we look forward to their continued support as we rapidly transition to later-stage clinical development."

Dr. Son joins Equillium from Allergan where he served as global regulatory affairs lead. At Equillium, Dr. Son will be responsible for a global regulatory strategy and execution across Equillium’s development programs to support regulatory approvals.

Mr. Lugo previously directed technical services and commercial contract manufacturing operations for U.S. and international drug substance and drug product process operations at AstraZeneca, and was vice president of manufacturing at Nielsen Biosciences. At Equillium, Mr. Lugo will oversee the CMC (chemistry manufacturing and controls), clinical production and commercial manufacturing operations.

Mr. Moore comes to Equillium with over 20 years of experience in investor relations and corporate communications, representing all niches of life sciences, at every stage of development. At Equillium, Mr. Moore will be responsible for leading the company’s communications strategy, corporate messaging and ongoing external communications with the financial community and other stakeholders.

On December 21, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS), reported topline data from the randomized Phase 3 ARIEL4 study of Rubraca, which met its primary endpoint of improved investigator-assessed progression-free survival (InvPFS) compared to chemotherapy in relapsed ovarian cancer patients with a tumor mutation of BRCA who have received two or more prior lines of chemotherapy (Press release, Clovis Oncology, DEC 21, 2020, View Source [SID1234573157]).

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"We are pleased with these topline results from the ARIEL4 trial, which confirm the clinical benefit of Rubraca versus chemotherapy, including platinum-based chemotherapy, as a treatment for women with BRCA mutation-positive advanced ovarian cancer, including patients who are platinum-resistant," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We look forward to sharing comprehensive results at an upcoming medical meeting."

The ARIEL4 study (NCT02855944) is a Phase 3 multicenter, randomized study evaluating Rubraca versus chemotherapy in platinum-sensitive, partially platinum-sensitive and platinum-resistant patients with relapsed ovarian cancer and a BRCA mutation (inclusive of germline and/or somatic) who have received two or more prior lines of chemotherapy. The primary endpoint of the study is InvPFS, with a step down analysis from the efficacy population (if significant) to the ITT population. The efficacy population comprised the group of patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation as determined by a blood test developed by Guardant Health. Development of reversion mutations that restore BRCA protein function are associated with resistance to platinum-based chemotherapies and PARP inhibitors in BRCA-mutant cancers, and these occur more frequently in platinum-resistant vs platinum-sensitive patients (13% and 2% respectively in the ARIEL2 study).i

Completion of ARIEL4 is a post-marketing commitment in the U.S. and EU.

349 women were enrolled in North and South America, Europe and Israel. The efficacy population (n=325) comprised the group of patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation. The rucaparib arm (n=220) successfully achieved statistical significance over the chemotherapy arm (n=105) for the primary endpoint of InvPFS with a hazard ratio of 0.639 (p=0.0010). The median PFS for the patients in the efficacy population treated with rucaparib was 7.4 months vs. 5.7 months among those who received chemotherapy.

In addition, in the ITT population (n=349), the rucaparib arm (n=233) successfully achieved statistical significance over the chemotherapy arm (n=116) for the primary endpoint of InvPFS with a hazard ratio of 0.665 (p=0.0017). The median PFS for the patients in the ITT population treated with rucaparib was 7.4 months vs. 5.7 months among those who received chemotherapy.

Patients with a BRCA reversion mutation represented 7 percent of patients enrolled in the study and as anticipated, InvPFS results for those patients showed limited benefit from Rubraca therapy.

An interim analysis of overall survival, a secondary endpoint in the study in which 51 percent of events have occurred in the ITT population, showed a trend toward an overall survival (OS) advantage in the chemotherapy arm, but was confounded by the high rate (64%) of per-protocol crossover to Rubraca following progression on chemotherapy. Importantly, an analysis of the ITT population of patients showed a trend toward an OS advantage for those patients who received Rubraca at any point in the trial versus those who did not.

Adverse events were consistent with the known safety profiles of Rubraca and chemotherapy.

The most common (>5%) treatment-emergent grade 3/4 adverse events (TEAEs) among all patients treated with rucaparib (n=232) in the ARIEL4 study were anemia/decreased hemoglobin (22%), neutropenia/decreased absolute neutrophil count (10%), asthenia/fatigue (8%), thrombocytopenia/decreased platelets (8%), and increased ALT/AST (8%).

"The ARIEL4 study verified that women with relapsed, BRCA mutation-positive advanced ovarian cancer, including those who are platinum-sensitive or -resistant, received benefit with rucaparib treatment when compared to chemotherapy," said Dr. Amit Oza, Head of the Division of Medical Oncology & Hematology, Medical Director of the Cancer Clinical Research Unit at Princess Margaret (PM) Cancer Centre, co-Director of the Drug Development Program at PM Cancer Centre, Senior Scientist at the Princess Margaret Cancer Centre, and Professor of Medicine at University of Toronto. "These results underscore the importance of rucaparib as a treatment option for women with BRCA-mutant advanced ovarian cancer."

Ovarian cancer ranks fifth in cancer deaths among women in the U.S.ii and EUiii. While there are a growing number of therapies to treat ovarian cancer, after initial therapy, 70-90% of U.S. womeniv with advanced disease will recur. In the EU, approximately 70% of patients experience a relapse within three years following initial therapy.v

"Ovarian cancer remains a lethal gynecologic cancer and there are limited treatment options for relapsed disease," said Dr. Rebecca Kristeleit, Co-Chief Investigator of ARIEL4 and Consultant Medical Oncologist, London, UK. "There is a need for therapies that can extend time to progression. The ARIEL4 data confirm the clinical relevance of BRCA reversion mutations and advance our understanding of how best to manage the treatment of women with advanced ovarian cancer."

Drs. Rebecca Kristeleit and Amit Oza are coordinating investigators on the ARIEL4 study. Clovis Oncology plans to provide an expanded description of the ARIEL4 results at a medical meeting in 2021.

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 Ovarian Cancer U.S. FDA Approved Indications

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.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have occurred 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.

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.

Click here for full Prescribing Information and additional Important Safety Information.

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.