CLOVIS ONCOLOGY INC.
CLOVIS ONCOLOGY INC.
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New Data Presented at ESMO Virtual Congress 2020 Highlight Breadth and Potential of Clovis Oncology Products and Pipeline

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Clovis Oncology, Inc. (NASDAQ: CLVS) today announced the data being presented as e-posters at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. These include initial data from the Phase 1b part of the LIO-1 study of lucitanib in combination with Opdivo, new analyses of data from the pivotal Rubraca ARIEL3 and TRITON2 studies, initial data from the Phase 1b part of the SEASTAR study arm of Rubraca with Trodelvy™ (sacituzumab govitecan-hziy), and the first presentation of preclinical data for FAP-2286 Clovis’ novel peptide-targeted radionuclide therapy.

“We are very pleased to present these encouraging initial datasets for our pipeline compounds lucitanib and FAP-2286 today, as well as data further characterizing and confirming the established safety profile of Rubraca in advanced ovarian and prostate cancers, which we believe provides additional, valuable information to physicians and their patients,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We are enthusiastic about the potential of our clinical development programs for each of our three compounds and remain committed to exploring the full depth and breadth of our pipeline to transform the cancer treatment landscape and hopefully improve outcomes for patients.”

Data presented today from the Phase 1b part of the Phase 1b/2 LIO-1 study in patients with an advanced solid tumor (n=17) have identified the recommended starting Phase 2 dose of oral lucitanib to be used in combination with Opdivo and have shown promising signs of antitumor activity. The recommended oral starting dose of lucitanib was established as 6 mg once daily, to be given in combination with Opdivo at a fixed dose of 480 mg intravenously (IV) once every 28 days. Across three dose levels studied (6 mg, 8 mg and 10 mg) of oral lucitanib in combination with intravenous (IV) Opdivo at (480 mg once every 28 days), only one dose-limiting toxicity of Grade 3 proteinuria was observed among 17 patients, and there were no apparent differences in treatment-emergent adverse event (TEAE) frequencies between dose levels. In this small patient population, TEAEs were consistent with those expected for lucitanib and Opdivo. Grade 3 TEAEs included hypertension (n=4), diarrhea (n=1), and proteinuria (n=1); treatment-emergent hypertension was otherwise grade 1 or 2 (n=4), and readily managed with close monitoring and early hypertensive therapy. No grade ≥4 adverse events were reported. Given lucitanib’s relatively large inter-patient pharmacokinetic variability, a safety-based dose-titration approach is being used for the Phase 2 part of the study to optimize lucitanib efficacy as well as safety and tolerability. Among the 17 patients treated, 15 were evaluable for RECIST response as of the efficacy cut-off date: these include one patient with a confirmed complete response, one patient with a confirmed partial response, 10 patients have had a best response of stable disease and three patients had progressive disease. As of August 11, 2020, seven of the 17 patients remained on study, including the two responders and five of the patients with stable disease.

“We have completed enrollment in the Phase 1b part of the LIO-1 trial, and have identified a dose of lucitanib to take into Phase 2 combined with nivolumab. The combination showed promising signs of activity in unselected solid tumors in patients with very advanced disease, including one patient with a confirmed complete response,” said Dr. Erika Hamilton, Director of the Breast and Gynecologic Research Program, Sarah Cannon Research Institute at Tennessee Oncology. “We were also encouraged by the initial safety profile, in particular as it relates to constitutional side effects, and hope to build on that with our dose-titration approach in the ongoing Phase 2 part of the LIO-1 study. This will provide greater understanding of what this combination may offer for the treatment of patients with gynecological cancers.”

In addition to data from the Phase 1b part of the LIO-1 study, a Trials in Progress (TiP) poster describing the study design of the Phase 2 part of LIO-1 was presented. The Phase 2 part of the study is currently enrolling patients to evaluate the efficacy and safety of the lucitanib and Opdivo combination in patients with advanced gynecological solid tumors, including ovarian, endometrial and cervical cancers. As described in the e-poster, a safety-based dose-titration approach is being used for lucitanib dosing to manage tolerability and maintain dose intensity.

Investigators also presented today new safety data analyses from the pivotal Rubraca studies ARIEL3 and pharmacokinetic (PK) analyses of TRITON2, providing additional information to healthcare professionals that can help support their ovarian and prostate cancer patients being treated with Rubraca.

The ARIEL3 data presented in an e-poster reinforce the overall safety profile of Rubraca as a maintenance treatment in patients with recurrent ovarian cancer. After two years of additional follow up for those patients who continued on treatment in the study, the safety profile remains consistent with previous reports, with no new safety signals identified. As of the current safety data cutoff (December 31, 2019), 33 of 372 and 1 of 189 patients in the safety population were still receiving Rubraca or placebo, respectively. Median treatment duration was 8.3 months in the Rubraca arm and 5.5 months in the placebo arm. Prevalence of any-grade nausea declined progressively over the 24-month evaluation period, and prevalence of any-grade anemia/decreased hemoglobin peaked at month 4, decreasing to a plateau after month 8. The first onset of frequently reported TEAEs generally occurred early in treatment (≤45 days). The median duration of the first event of frequently reported TEAEs was generally <60 days.

Population pharmacokinetic (PK) analyses of 199 men with mCRPC receiving Rubraca in the TRITON2 study suggest there is no difference in Rubraca PK in men with mCRPC and women with ovarian cancer based on a comparison to a previously-developed model that used data from 454 women with ovarian cancer treated with Rubraca. The data in men with mCRPC show that differences among patients in the amount of Rubraca in the blood after administration of Rubraca at a dose of 600 mg twice daily did not appear to impact the efficacy of treatment. Also, a higher maximum concentration of Rubraca in the blood was not associated with increased rates of most safety endpoints analyzed, including hematologic adverse events. These PK data and exposure and safety/efficacy correlations using data from the TRITON2 study support the use of Rubraca in eligible mCRPC patients with a starting dose of 600 mg twice daily. TRITON2 served as the pivotal data supporting the May 2020 FDA approval of Rubraca as the first PARP inhibitor for patients with advanced mCRPC associated with a BRCA mutation.

Investigators also presented in an e-poster initial data from the arm of the Phase 1b/2 SEASTAR study evaluating Rubraca in combination with Trodelvy in patients with advanced solid tumors (n=6). Data from the Phase 1b part of the study suggest encouraging initial antitumor activity for the novel combination, including patients with prior PARP inhibitor exposure and without a deleterious homologous recombination repair gene mutation. Despite early toxicities, including dose-limiting neutropenia in two of the three patients in the higher dose cohort, all six patients continued treatment for at least 12 weeks, with side effects effectively managed with dose modification and/or growth factor support. One patient remained on treatment as of the August 11, 2020 data cut-off date. All patients had a best response of stable disease or better, including three patients with a confirmed partial response (all three had been previously treated with a PARP inhibitor).

And finally, the first data from a preclinical evaluation of FAP-2286, Clovis’ novel peptide-targeted radionuclide therapy to fibroblast activation protein (FAP) were presented in an e-poster. The data show that FAP-2286 potently and selectively binds FAP. FAP is highly expressed in cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers and, in some cancers, its expression has also been observed in the tumor cells. Compelling anti-tumor activity was observed with 177Lu-FAP-2286 (Lutetium-177 conjugated to FAP-2286 for therapeutic use) in FAP-expressing tumor models. Clovis Oncology plans to submit two Investigational New Drug (IND) applications in late 2020 for use of this novel radionuclide therapy as an imaging and treatment agent, respectively, and the Company has planned clinical studies in a broad spectrum of FAP-positive cancers.

Each of Clovis Oncology’s e-posters described are available online at www.clovisoncology.com/pipeline/scientific-presentations.

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 peptide-targeted radionuclide therapy (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 Oncology is planning to submit an investigational new drug application (IND) for FAP-2286 in the second half of 2020 and conduct the global clinical trials. Clovis Oncology holds U.S. and global rights, excluding Europe.

FAP-2286 is an unlicensed medical product.

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.

To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management. Examples of forward-looking statements contained in this press release include, among others, statements regarding our expectations for submission of regulatory filings, the timing and pace of commencement of and enrollment in our clinical trials, including those being planned or conducted in collaboration with partners, the potential results of such clinical trials, our expectations regarding the suitability of each of Rubraca, lucitanib and FAP-2286 for, and our plans to develop each of Rubraca, lucitanib and FAP-2286 in, additional indications and tumor types, and our expectations regarding the outcomes of early studies or trials supporting further development, both non-clinical and clinical. Such forward-looking statements involve substantial risks and uncertainties that could cause our future results, performance or achievements to differ significantly from that expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in our clinical development programs for our drug candidates and those of our partners, whether future study results will be consistent with study findings to date, the timing of availability of data from our clinical trials and the initiation, enrollment, timing and results of our planned clinical trials and the corresponding development pathways, effectiveness and suitability of diagnostic tests, the risk that final results of ongoing trials may differ from initial or interim results as a result of factors such as final results from a larger patient population may be different from initial or interim results from a smaller patient population, the risk that additional pre-clinical or clinical studies may not support further development in certain additional indications or tumor types, and actions by the FDA, the EMA or other regulatory authorities regarding data required to support drug applications and whether to approve drug applications. Clovis Oncology does not undertake to update or revise any forward-looking statements. A further description of risks and uncertainties can be found in Clovis Oncology’s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and its reports on Form 10-Q and Form 8-K.

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