- The ARIEL4 study met its primary endpoint, showing a statistically significant improvement in progression-free survival for Rubraca versus chemotherapy
- The safety of Rubraca observed in the ARIEL4 study was highly consistent with both the U.S. and EU labels
- An expanded description of the ARIEL4 study results will be submitted for presentation at an upcoming medical meeting
BOULDER, CO, USA I December 21, 2020 I Clovis Oncology, Inc. (NASDAQ: CLVS), today announced 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.
“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.
About Clovis Oncology
Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the U.S., Europe and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the U.S. and Europe. Please visit www.clovisoncology.com for more information.
i Lin et al. BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma. Cancer Discovery. 2019. https://cancerdiscovery.aacrjournals.org/content/9/2/210. Last accessed December 2020.
ii American Cancer Society. Cancer Facts & Figures 2018. Atlanta, GA: American Cancer Society; 2018.
iii World Health Organization. GLOBOCAN: estimated cancer incidence, mortality and prevalence worldwide in 2018. Available at http://gco.iarc.fr/. Last accessed December 2020.
iv Ovarian Cancer Research Alliance (OCRA) https://ocrahope.org/patients/about-ovarian-cancer/recurrence/ Last accessed December 2020.
v Ledermann J et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl 6):vi24-32.
SOURCE: Rubraca
Post Views: 30
- The ARIEL4 study met its primary endpoint, showing a statistically significant improvement in progression-free survival for Rubraca versus chemotherapy
- The safety of Rubraca observed in the ARIEL4 study was highly consistent with both the U.S. and EU labels
- An expanded description of the ARIEL4 study results will be submitted for presentation at an upcoming medical meeting
BOULDER, CO, USA I December 21, 2020 I Clovis Oncology, Inc. (NASDAQ: CLVS), today announced 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.
“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.
About Clovis Oncology
Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the U.S., Europe and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the U.S. and Europe. Please visit www.clovisoncology.com for more information.
i Lin et al. BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma. Cancer Discovery. 2019. https://cancerdiscovery.aacrjournals.org/content/9/2/210. Last accessed December 2020.
ii American Cancer Society. Cancer Facts & Figures 2018. Atlanta, GA: American Cancer Society; 2018.
iii World Health Organization. GLOBOCAN: estimated cancer incidence, mortality and prevalence worldwide in 2018. Available at http://gco.iarc.fr/. Last accessed December 2020.
iv Ovarian Cancer Research Alliance (OCRA) https://ocrahope.org/patients/about-ovarian-cancer/recurrence/ Last accessed December 2020.
v Ledermann J et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl 6):vi24-32.
SOURCE: Rubraca
Post Views: 30
