On May 19, 2021Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that kit will report initial data from its Phase 2 SPEARHEAD-1 trial, with afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress (Press release, Adaptimmune, MAY 19, 2021, View Source [SID1234580334]). Full abstracts were released online today. Data will be presented in an oral presentation by Dr. Sandra D’Angelo of the Memorial Sloan Kettering Cancer Center (Abstract #11504) on June 4th.

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"Patients are seeing substantial benefit from afami-cel in SPEARHEAD-1 across a broad range of cell doses and levels of MAGE-A4 expression," said Adrian Rawcliffe, Adaptimmune Chief Executive Officer. "We have shown a high response rate and these responses are still evolving in many patients with increasing depths of response over time and encouraging durability. I am confident that SPEARHEAD-1 will support our BLA submission next year and offer a life-changing treatment for people with synovial sarcoma."

"Initial data from SPEARHEAD-1 indicate that afami-cel has the potential to offer people with synovial sarcoma a promising new treatment option where there is currently a great unmet medical need," said Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center. "As clinicians, we want to be able to provide a treatment regimen that can help offer a better quality of life."

SPEARHEAD-1 data will be presented at the time of the oral presentation scheduled for June 4th during the sarcoma session taking place from 1:30 p.m. to 4:30 p.m. EDT.

Afami-cel is efficacious and well-tolerated in heavily pre-treated patients based on initial data

At the time of data cut-off (March 29, 2021), 37 patients had received afami-cel (32 with synovial sarcoma, 5 with myxoid/ round cell liposarcoma [MRCLS])
Of the 37 patients who had received afami-cel, 4 patients were pending first efficacy assessment, and 33 had at least one scan as of data cut off (29 with synovial sarcoma, 4 with MRCLS)
The overall response rate1 was 39.3% (13/33), 41.4% (12/29) for synovial sarcoma; 25.0% (1/4) for MRCLS
Of the 29 patients with synovial sarcoma with at least one scan, 2 had complete responses (CRs), 10 had partial responses (PRs), 13 had stable disease (SD), 4 had progressive disease (PD)
The disease control rate for people with synovial sarcoma was 86.2% (25/29) (defined as either response or stable disease)
Of the 4 patients with MRCLS with at least one scan, 1 patient had a partial response, 2 had stable disease, and 1 had progressive disease
Objective responses have been reported across a wide range of cell doses and MAGE-A4 antigen expression levels
Initial durability data is encouraging, and the median duration of response has not been reached
To date, the safety profile of afami-cel has been favorable, with mainly low-grade cytokine release syndrome and tolerable/reversible hematologic toxicities.
Overview of SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a Phase 1 trial (CTOS 2020).

Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only, which will be used to support the BLA filing next year. No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses.

Eligible patients were ≥ 16 and < 75 years, HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells that were ≥ 2+ by immunohistochemistry. Eligible patients received afami-cel doses between 1–10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.

The primary endpoint is overall response rate per RECIST v1.1 by independent review. The primary endpoint will be evaluated using a one-sided exact-based Clopper-Pearson 97.5% confidence interval (CI). If the lower bound of the CI exceeds the response rate reported with historical second line therapy(ies), the trial will have met the pre-specified threshold for demonstrating efficacy.

An independent Data Safety Monitoring Board reviews ongoing safety and benefit:risk during the interventional phase of the trial.

On May 19, 2021 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it launched an anticancer agent/antimicrotubule binding anti-CD79b monoclonal antibody Polivy intravenous infusion 30 mg and 140 mg [generic name: polatuzumab vedotin (genetical recombination)] for the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (Press release, Chugai, MAY 19, 2021, View Source [SID1234580237]). Polivy had been approved by the Ministry of Health, Labour and Welfare (MHLW) on March 23, 2021 and was listed on the national health insurance (NHI) reimbursement price list today.

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"We are very pleased to launch Polivy as a new treatment for relapsed or refractory DLBCL," said Chugai’s President and CEO Dr. Osamu Okuda. "R/R DLBCL represents a high unmet medical need given the limited treatment options. We are committed to providing information in order to promote appropriate use of this first-in-class anti-CD79b antibody-drug conjugate (ADC) so that we may contribute to better treatment for patients."

The approval is based on data including the results from a multicenter overseas phase Ib/II clinical study (GO29365) that evaluated the efficacy and safety of Polivy in combination with bendamustine and rituximab (BR therapy) compared to BR therapy alone, and a multicenter, single-arm Japanese phase II study (JO40762/P-DRIVE study) that evaluated the efficacy and safety of Polivy in combination with BR therapy in R/R DLBCL.

A double-blind, placebo-controlled global phase III study (GO39942/POLARIX study) is ongoing for untreated DLBCL to examine the efficacy and safety of Polivy in combination with rituximab plus cyclophosphamide, doxorubicin, prednisolone (R-CHP) compared to rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP).

[Reference information]
Chugai Obtains Approval for Polivy for the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma (Press release issued by Chugai on March 23, 2021)
View Source

Polatuzumab Vedotin Achieved Primary Endpoint in the Japanese Phase II study for Relapsed or Refractory Diffuse Large B-cell Lymphoma (Press release issued by Chugai on February 13, 2020)
View Source

Approval information

Product name:
Polivy Intravenous Infusion 30 mg
Polivy Intravenous Infusion 140 mg

Generic name: polatuzumab vedotin (genetical recombination)

Intended uses or indications: Relapsed or refractory diffuse large B-cell lymphoma

Dosage and administration:
The usual adult dosage is 1.8 mg/kg (body weight) polatuzumab vedotin (genetical recombination) administered by intravenous infusion every 3 weeks for 6 doses, in combination with bendamustine hydrochloride and rituximab (genetical recombination). If the first infusion is well tolerated after 90 minutes, subsequent infusions may be administered over a shorter time of at least 30 minutes. Reduce the dose as necessary in accordance with the patient’s condition.

Date of approval: March 23, 2021

Date of NHI reimbursement price listing: May 19, 2021

Date of launch: May 19, 2021

Drug price:
Polivy Intravenous Infusion 30 mg JPY 298,825/vial
Polivy Intravenous Infusion 140 mg JPY 1,364,330/vial

About GO29365 study1)
GO29365 is a global, phase Ib/II study evaluating the safety and tolerability of Polivy in combination with bendamustine and rituximab (BR therapy) or obinutuzumab (BG therapy) in R/R follicular lymphoma or DLBCL. In the phase II randomized part of the study with 80 DLBCL patients, the efficacy and safety of Polivy in combination with BR therapy were studied compared to BR therapy alone. The primary endpoint was complete response at the point of primary response assessment as evaluated by an independent assessment committee using PET-CT. Patients received six cycles of treatment, spaced three weeks apart.

About JO40762 (P-DRIVE) study
JO40762 (P-DRIVE) is an open label, single-arm study investigating Polivy in combination with BR therapy in 35 patients with R/R DLBCL. Primary endpoint is investigator’s assessment of CRR by PET-CT at the timing of primary response assessment. Patients received six cycles of treatment, spaced three weeks apart.

About Polivy
Polatuzumab vedotin was developed by Roche using Seattle Genetics’ ADC technology. It is a first-in-class anti-CD79b antibody-drug conjugate (ADC), comprising the anti-CD79b humanized monoclonal antibody and a tubulin polymerization inhibitor attached together using a linker. The CD79b protein is expressed specifically in the majority of B-cells, making it a promising target for the development of new therapies2,3). Polatuzumab vedotin binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to suppress the effects on normal cells4,5). Polatuzumab vedotin was granted accelerated approval in the US in June 2019 and conditional marketing authorization in the EU in January 2020, respectively.

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is one of the histologic subtypes of non-Hodgkin’s lymphoma (NHL), which is categorized as an aggressive disease that progresses on a monthly basis. DLBCL is the most common form of NHL, accounting for 30-40 percent of NHL, which is equivalent to about 23,000-32,000 patients6-10). DLBCL frequently occurs in middle-aged and older people, mainly in their 60’s11). The median age at diagnosis has been reported to be 6412).

The combination of rituximab and chemotherapy is the standard therapy for untreated DLBCL; however, recurrence has been observed in about 40% of patients due to insufficient therapeutic effect13). In addition, although autologous stem cell transplantation (ASCT) is recommended for eligible patients with recurrent or refractory DLBCL, ASCT cannot be performed in about half of these patients due to failure of salvage chemotherapy prior to ASCT14). Furthermore, no standard therapy has been established for patients ineligible for ASCT due to reasons including age or complications15). Therefore, more useful new treatment options for relapsed or refractory DLBCL are in great need.

Salvage chemotherapy: Salvage chemotherapy or salvage therapy is used to treat patients with hematologic malignancy who experienced no therapeutic effects (refractory), or recurrence/relapse of the disease. Applicable treatment may vary depending on the type of cancer. Combination therapies of multiple drugs including anticancer agents16) are generally used.

Trademarks used or mentioned in this release are protected by law.

On May 19, 2021 Dynavax Technologies Corporation (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported that Ryan Spencer, Chief Executive Officer, will participate in a virtual fireside chat at the William Blair 41th Annual Growth Stock Conference on Tuesday, June 1, 2021 at 2:40 p.m. C.T (Press release, Dynavax Technologies, MAY 19, 2021, View Source [SID1234580254]).

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The presentation will be webcast and may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at View Source

On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported results from a randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab (ERBITUX), an EGFR-targeted antibody, in patients who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab (pan-refractory) with metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, AVEO, MAY 19, 2021, View Source [SID1234580271]). Ficlatuzumab is AVEO’s potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF). The results will be presented by lead investigator Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Deputy Director, University of Arizona Cancer Center, at a poster discussion session of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 4-8 in a virtual setting.

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"Human papillomavirus (HPV) negative HNSCC is associated with poorer outcomes compared to HPV positive disease, particularly in pan-refractory disease, where there are currently no effective treatment options," said Professor Bauman. "Crosstalk between EGFR and HGF/cMet pathways is a known tumor intrinsic resistance mechanism, and HGF expression is known to be high in HPV negative disease, suggesting that the simultaneous inhibition of these pathways with cetuximab and ficlatuzumab could enhance anti-cancer response in this population. Results from this study are highly encouraging, with notable activity in pan-refractory, HPV negative disease warranting Phase 3 investigation."

"Results in patients with HPV negative disease who received ficlatuzumab and cetuximab produced prolonged progression free survival (PFS) and a response rate of 38%, which included two (18%) complete responses (CRs). These results suggest the combination has the potential to play a meaningful role in the treatment and the ultimate quality of life of patients with relapsed/metastatic HNSCC," said Michael Bailey, president and chief executive officer of AVEO. "The results compare favorably to historical controls of cetuximab in earlier lines of treatment. After receiving FDA feedback, we look forward to making a go/no-go decision by mid-year on the initiation of a Phase 3 study in an HPV negative HNSCC patient population, which we would expect to initiate in the first half of 2022, upon the availability of clinical drug supply."

In the Phase 2 study, a total of 60 patients with metastatic HNSCC who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab were randomized 1:1 to receive either ficlatuzumab alone (20 mg/kg IV) or ficlatuzumab in combination with cetuximab (500 mg/m2 IV) every two weeks. The ficlatuzumab/cetuximab combination arm met the study’s primary endpoint of median PFS, with the 32 evaluable patients in the arm demonstrating a median PFS of 3.6 months (lower bound 90% confidence interval [CI] 2.3 months; p=0.04), and 1.8 months (lower bound 90% CI: 1.7 months) for the 26 evaluable patients receiving ficlatuzumab alone. For the key secondary endpoint of overall response rate (ORR), the combination arm demonstrated an ORR of 19%, and 4% for ficlatuzumab alone.

Enrolled patients were stratified by HPV status, as HPV negative patients are known to have poorer outcomes. In an exploratory comparison of the HPV positive (n=16) and HPV negative (n=16) subgroups of the combination arm, HPV negative patients demonstrated both a superior ORR of 38% (versus 0% for HPV positive, p=0.02), with two CRs and four partial responses, and a median PFS of 4.1 months (versus 2.3 months for HPV positive, p=0.03). These results reflect updated data from those available at the time of abstract submission.

The combination of ficlatuzumab and cetuximab was generally well-tolerated with expected class toxicities from HGF/cMet inhibitors observed, including common adverse events of edema and hypoalbuminemia, and an uncommon adverse event of pneumonitis. Two treatment related deaths occurred, including pneumonitis (ficlatuzumab arm) and cardiopulmonary arrest (combination arm).

A copy of the poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

ASCO Presentation Details

Title: Randomized Phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).
Presenter: Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Associate Director of Translational Research, University of Arizona Cancer Center
Abstract: 6015
Track: Head and Neck Cancer
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
About Ficlatuzumab

Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) immunoglobulin G1 (IgG1) inhibitory antibody that binds to the HGF ligand with high affinity and specificity. HGF is the natural ligand of c-Met and blocking HGF inhibits signaling through the HGF/c-Met signaling pathway. Ficlatuzumab is currently being evaluated in squamous cell carcinoma of the head and neck (HNSCC) and metastatic pancreatic ductal cancer (PDAC).

On May 19, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that four abstracts featuring data from clinical studies evaluating Rubraca and/or lucitanib and one abstract on real world data of PARP inhibitor usage, will be presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held virtually, June 4-8, 2021 (Press release, Clovis Oncology, MAY 19, 2021, View Source [SID1234580287]).

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"We remain committed to understanding how Rubraca and lucitanib may benefit patients with cancer, and the data presented at ASCO (Free ASCO Whitepaper) further enhance our understanding of their potential benefit in different patient populations and solid tumor types," said Patrick J. Mahaffy, President and CEO of Clovis Oncology.

The following Clovis-sponsored full abstracts are available as of May 19 at 5:00 pm ET on ASCO (Free ASCO Whitepaper)’s Meeting Library. Clovis-sponsored posters and supplemental information will be available as of June 3at 5:00 pm ET at View Source

Rubraca

Abstract #5517: Subgroup Analysis of Rucaparib Versus Chemotherapy as Treatment for BRCA-mutated, Advanced, Relapsed Ovarian Carcinoma: Effect of Platinum Sensitivity in the Randomized, Phase 3 Study ARIEL4

Lead Author: Amit M. Oza, MD, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
Poster Discussion Session: Gynecologic Cancer
Date/Time: June 4 at 9:00 am ET
Key Takeaways: Results from this exploratory subgroup analysis of the Phase 3 ARIEL4 trial demonstrate that patients treated with Rubraca had comparable or longer PFS vs. standard-of-care platinum-chemotherapy across all platinum status subgroups. Safety profiles for Rubraca and chemotherapy across the subgroups were consistent with known safety profiles of these agents. These results suggest that Rubraca is an effective treatment option for heavily pretreated patients with BRCA-mutated, advanced, relapsed ovarian cancer as compared to chemotherapy, regardless of their sensitivity to platinum-based therapy.
Abstract #5537: Clinical and Molecular Characteristics of ARIEL3 Patients Who Derived Exceptional Benefit from Rucaparib Maintenance Treatment for High-grade Ovarian Cancer (HGOC)

Lead Author: Tanya Kwan, PhD, Clovis Oncology, Inc., Boulder, Colorado, USA
Poster Session: Gynecologic Cancer
Date/Time: June 4 at 9:00 am ET
Key Takeaways: In the Phase 3 ARIEL3 trial, exceptional benefit (progression-free survival ≥2 years) was more common in, but not exclusive to, patients with favorable clinical characteristics and known mechanisms of PARP inhibitor sensitivity, including mutations of
BRCA1/2
and
RAD51C/D
. These results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with high-grade ovarian cancer. In all, 21% (79/375) of patients in the rucaparib arm derived exceptional benefit versus only 2% (4/189) in the placebo arm of the trial. Among rucaparib-treated patients, incidence rates of the most common TEAEs were generally consistent between the exceptional benefit subgroup and the overall ARIEL3 patient population.
Rubraca in Combination with Lucitanib

Abstract #3102: Phase 1b/2 SEASTAR Trial: Safety, Pharmacokinetics, and Preliminary Efficacy of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Rucaparib and Angiogenesis Inhibitor Lucitanib in Patients with Advanced Solid Tumors

Lead Author: Ecaterina E. Dumbrava, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Poster Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date/Time: June 4 at 9:00 am ET
Key Takeaways: Initial findings suggest that rucaparib plus lucitanib has an acceptable safety profile, and there was some evidence of effect on tumor and disease stabilization among patients with measurable disease, with a 23.5% disease control rate. A maximum tolerated dose for the combination was not established, and no drug-drug interactions were observed. These data suggest the combination of a PARP inhibitor and an angiogenesis inhibitor is feasible and may merit further evaluation.
Lucitanib in Combination with Nivolumab

Abstract #5538: LIO-1: Lucitanib + Nivolumab in Patients with Advanced Solid Tumors—Updated Phase 1b Results and Initial Experience in Phase 2 Ovarian Cancer Cohort

Lead Author: Erika Hamilton, MD, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee, USA
Poster Session: Gynecologic Cancer
Date/Time: June 4 at 9:00 am ET
Key Takeaways: Data from the Phase 1b LIO-1 trial identified the Phase 2 starting dose of the combination and updated Phase 1b efficacy data suggest that lucitanib plus nivolumab has promising antitumor activity (47.1% disease control rate) with a manageable safety profile in patients with advanced solid tumors with no satisfactory treatment options. The Phase 2 study is currently assessing four cohorts of patients with advanced gynecologic malignancies. Interim results from one of these, non-clear cell ovarian cancer (OC) are reported here. 70.8% of patients had received at least 3 previous therapy lines, and 29.2% had primary platinum resistant disease. In 22 evaluable patients, the disease control rate was 31.8% including one confirmed PR. The safety profile of the combination was consistent with that reported in the Phase 1b portion of the study. In addition, the data support the individualized lucitanib dose-titration strategy. While evidence of clinical activity has been observed, Clovis does not believe that the interim efficacy data support further development in non-clear cell OC. Enrollment to the other cohorts continues.
HEOR

Abstract #e18702: Real-world Data Analysis of the Utilization of Second-Line Maintenance Therapy for Patients with Advanced Ovarian Cancer

Lead Author: Robert Reid, MD, FACP, US Oncology, Virginia Cancer Specialists, Fairfax, Virginia, USA
Accessible as e-publication only
Key Takeaways: Real world data from the iKnowMed electronic database of the US Oncology Network (including >470 sites) found that fewer than half of eligible ovarian cancer patients receive second-line maintenance treatment, despite treatment guidelines recommending its usage. In addition, the proportion of patients receiving 2L PARPi maintenance increased from 17% in 2018 to 34% in 2019 but decreased to 22% in 2020.
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 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.

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).

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.