Clovis Oncology Highlights Rubraca® (Rucaparib) and FAP-2286 Data to be Presented at 2022 ASCO Annual Meeting

Includes presentation of additional late-breaking Phase 3 ATHENA-MONO trial data as complement to previously announced topline data

Clovis Oncology, Inc. (NASDAQ: CLVS), announced today that seven abstracts from the company’s pipeline, including late-breaking data from the ATHENA-MONO Phase 3 clinical trial evaluating Rubraca monotherapy versus placebo and imaging of solid tumors using FAP-2286, will be presented in oral and poster sessions during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2022, in Chicago. Three additional retrospective analyses evaluating Rubraca and PARP inhibitors will be published online during the meeting.

“The wealth of data being presented during ASCO, including more detailed analyses of the positive results from the ATHENA-MONO study of Rubraca monotherapy versus placebo in first-line maintenance treatment for ovarian cancer, adds to the breadth of knowledge demonstrating that Rubraca is an important part of treatment for patients regardless of biomarker status,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “Additionally, we look forward to new imaging data of FAP-2286 in solid tumors, an important component in understanding the solid tumor types where FAP-2286 may offer clinical benefit for patients.”

The following non late breaker Clovis-sponsored and Clovis-supported abstracts will be available as of May 26 at 5:00 pm EDT on ASCO's Meeting Library. The Clovis-sponsored late breaker abstract will be available as of June 6 at 8:00 a.m. EDT, and the posters and supplemental materials for all abstracts will be available on the day and at the time of presentation in the ASCO Program. In addition, Clovis-sponsored posters and supplemental materials can be found at https://clovisoncology.com/pipeline/scientific-presentations/ on the day and time of presentation.

Rubraca

Company-Sponsored Abstracts:

Abstract #LBA5500: ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer

• Lead Author: Bradley J. Monk., M.D., GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, USA
• Oral Abstract Session: Gynecologic Cancer
• Date/Time: June 6, 9:00 a.m. – 12:00 p.m. EDT, presentation 9:00 – 9:12 a.m. EDT

Abstract #5544: Efficacy and safety of rucaparib maintenance treatment in patients from ARIEL3 with platinum-sensitive, recurrent ovarian carcinoma not associated with homologous recombination deficiency

• Lead Author: Robert L. Coleman, FACS, M.D., FACOG, FASCO, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• Poster Session: Gynecologic Cancer
• Date/Time: June 4, 2:15 – 5:15 p.m. EDT

Company-Supported Abstracts:

Abstract #TPS9138: A Phase I/II multisite study of rucaparib and pembrolizumab maintenance therapy in stage IV non-squamous non-small cell lung cancer after initial therapy with carboplatin, pemetrexed, and pembrolizumab

• Lead Author: Angel Qin, BS, M.D., University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA
• Poster Session: Lung Cancer—Non-Small Cell Metastatic
• Date/Time: June 6, 9:00 a.m. – 12:00 p.m. EDT

Abstract #TPS5107: Alliance A031902 (CASPAR): A randomized, phase (ph) 3 trial of enzalutamide with rucaparib/placebo in first-line metastatic castration-resistant prostate cancer (mCRPC)

• Lead Author: Arpit Rao, M.D., Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
• Poster Session: Genitourinary Cancer—Prostate, Testicular, and Penile
• Date/Time: June 6, 2:15 – 5:15 p.m. EDT

Abstract #5510: An open label, nonrandomized, multisite phase II trial combining bevacizumab, atezolizumab, and rucaparib for the treatment of previously treated recurrent and progressive endometrial cancer

• Lead Author: William Hampton Bradley, M.D., Froedtert and the Medical College of Wisconsin, Wauwatosa, WI, USA
• Clinical Science Symposium: Molecular-Based Treatment for Endometrial Cancer
• Date/Time: June 7, 9:00 – 10:30 a.m. EDT

ASCO Publication-Only Abstracts:

Abstract #e17562: Clinical experience with rucaparib after prior PARPi treatment: a subanalysis from the rucaparib access program in Spain by GEICO

• Lead Author: Alfonso Yubero, M.D., Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

Abstract #e17598: Clinical insights from the rucaparib access program in Spain: a sub-analysis of long-term responders by GEICO

• Lead Author: Alfonso Yubero, M.D., Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

Abstract #e18812: Real-world progression-free and overall survival for patients with advanced ovarian cancer utilizing PARP inhibitor second-line maintenance therapy vs active surveillance

• Lead Author: Robert Reid, M.D., US Oncology, Medical Oncology, Virginia Cancer Specialists, Fairfax, VA, USA

FAP-2286

Company-Supported Abstract:

Abstract #3059: Imaging of solid tumors using ⁶⁸Ga-FAP-2286

• Lead Author: Thomas A. Hope, M.D., Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
• Poster Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
• Date/Time: June 5, 9:00 a.m. – 12:00 p.m. EDT

For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program, click here.

Lucitanib

Company-Sponsored Abstract:

Abstract #5517: Efficacy and safety of lucitanib + nivolumab in patients with advanced gynecologic malignancies: Phase 2 results from the LIO-1 study (NCT04042116; ENGOT-GYN3/AGO/LIO)

• Lead Author: Manish R. Patel, M.D., Drug Development Unit, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA
• Poster Discussion Session: Gynecologic Cancer
• Date/Time: June 4, 5:30 – 7:00 p.m. EDT
• Panel Q&A featuring Dr. Patel: 6:04 – 6:14 p.m. EDT

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 US and Europe.

Rubraca Ovarian Cancer US 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.

Please Click here for full Prescribing Information for Rubraca.

You may also report side effects to Clovis Oncology, Inc. at 1-415-409-7220 (US toll) or 1-844-CLVS-ONC (1-844-258-7662; US toll-free).

Rubraca (rucaparib) European Union (EU) including Northern Ireland, and Great Britain (GB) 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 EU SmPC (including for Northern Ireland). Click here to access the current GB SmPC.

Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

About the ATHENA Clinical Trial

ATHENA (GOG 3020/ENGOT-ov45) (NCT03522246) is an international, randomized, double-blind, phase III trial consisting of two separate and fully independently powered study comparisons evaluating Rubraca monotherapy (ATHENA-MONO) and Rubraca in combination with nivolumab (ATHENA-COMBO) as maintenance treatment for patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. ATHENA enrolled approximately 1000 patients across 24 countries, all women with newly diagnosed ovarian cancer who responded to their first-line chemotherapy. The trial completed accrual in 2020 and was conducted in association with the Gynecologic Oncology Group (GOG) in the US and the European Network of Gynaecological Oncological Trial groups (ENGOT) in Europe. GOG and ENGOT are the two largest cooperative groups in the US and Europe dedicated to the treatment of gynecological cancers.

ATHENA-MONO is evaluating the benefit of Rubraca monotherapy versus placebo in 538 women in this patient population. The primary efficacy analysis evaluated two prospectively defined molecular sub-groups in a step-down manner: 1) HRD-positive (inclusive of BRCA mutant) tumors, and 2) the intent-to-treat population, or all patients treated in ATHENA-MONO.

The ATHENA-COMBO portion of the trial, anticipated to readout in Q1 2023, is evaluating the magnitude of benefit of adding Opdivo (nivolumab) to Rubraca monotherapy in the ovarian cancer first-line maintenance treatment setting. ATHENA-COMBO is anticipated to be the first Phase 3 dataset to readout evaluating the combination of a PARP inhibitor and an immune checkpoint inhibitor as maintenance treatment following completion and response to front-line chemotherapy.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as “theranostics.” Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors. The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (¹⁷⁷Lu-FAP-2286). FAP-2286 labeled with gallium-68 (⁶⁸Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

About Lucitanib

Lucitanib is an investigational angiogenesis inhibitor, which inhibits vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/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. Clovis holds global rights for lucitanib excluding China.

Lucitanib 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 US, 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 US 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 made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements contained in this press release include, among others, statements of our intentions and expectations for our development and discovery programs, including the timing and pace of pre-clinical development, plans for and expected timing and pace of clinical development, plans for additional applications of Rubraca, lucitanib and the FAP-2286 peptide, including potential indications, tumor types and combination trials, plans for presentation of data and regulatory plans with respect to Rubraca, lucitanib and FAP-2286. Such forward-looking statements involve substantial risks and uncertainties that could cause Clovis Oncology’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in drug discovery and pre-clinical and clinical development, including the outcome of pre-clinical studies and clinical trials, whether initial results, findings or research will support future studies or development, whether future study results will be consistent with previous study findings or other results, including pre-clinical studies, results in named-patient or similar programs or clinical trials, whether additional studies not originally contemplated are determined to be necessary, the timing of initiation, enrollment and completion of planned studies 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 undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Clovis Oncology’s Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and its other reports filed with the Securities and Exchange Commission.

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