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LONDON, May 20, 2020 /PRNewswire/ -- As part of its ongoing work to advance potentially transformational medicines, GlaxoSmithKline plc will present new data at the upcoming 2020 American Society of Clinical Oncology (ASCO) Annual Meeting from 29-31 May 2020. The depth and breadth of the presentations represent GSK's progress in helping people affected by cancer achieve better outcomes and build on the recent US Food and Drug Administration (FDA) approval of a new indication for Zejula^® (niraparib).

GSK, a leader in oncology R&D, has advanced its innovative pipeline by focusing on science related to the immune system, the use of human genetics and cutting-edge technologies that will advance the next wave of cancer therapies with the potential to transform outcomes for patients. At this year's ASCO meeting, the company will showcase presentations on investigational therapies, including belantamab mafodotin, an antibody drug conjugate for multiple myeloma,ⁱ and GSK3359609, an inducible T-cell co-stimulator (ICOS) agonist for patients with recurrent or metastatic head and neck squamous cell carcinoma.

Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: "These are challenging times and while we are working to combat the COVID-19 pandemic, we are also continuing to progress our goal of supporting patients with cancer by developing and delivering transformational medicines that may help to improve survival and bring us closer to potentially achieving cures. We're pleased to share this progress with our peers at ASCO, with the knowledge that there is more to come as we work to outpace the cancers we fight."

Investigational Targeting of BCMA in Relapsed/Refractory Multiple Myeloma
B-cell maturation antigen (BCMA) is universally expressed in patients with multiple myeloma, and targeting this cell-surface protein has become an actively researched investigational approach in this cancer.ⁱⁱ Data from the extensive DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) development programme of belantamab mafodotin will evaluate its potential in different relapsed/refractory and newly diagnosed multiple myeloma treatment settings. Presentations of interest include:

• Updated nine-month results from the pivotal DREAMM-2 study of single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma refractory to proteasome inhibitors, immunomodulatory agents and refractory and/or intolerant to anti-CD38 monoclonal antibodies (abstract #8536; presenter, Lonial S).
• Preliminary data from the DREAMM-6 study on the safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (abstract #8502; presenter, Nooka A).

Progress in Ovarian Cancer
In April, the FDA approved Zejula, an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as a monotherapy maintenance treatment for women with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. At ASCO, five presentations will further explore niraparib's utility in ovarian cancer.

Ongoing Investigation in Head and Neck Squamous Cell Carcinoma
GSK3359609 is an investigational ICOS agonist antibody that is designed to selectively enhance T-cell function and enable anti-tumour responses in patients. Presentations at ASCO report findings on our ongoing studies into the anti-tumour potential of targeting the ICOS receptor through this agonist antibody alone and in combination with immune checkpoint therapies for the treatment of head and neck squamous cell carcinoma.

• Updated Analysis of the Inducible T-cell Co-stimulatory Receptor Agonist (ICOS), GSK3359609 (GSK609), Combination with Pembrolizumab (PE) in Patients (pts) with Anti-PD-1/L1 Treatment-naïve Head and Neck Squamous Cell Carcinoma (HNSCC) (abstract #6517; presenter, Angevin E).
• INDUCE-1: Report on Safety Run-in Cohorts Combining the Inducible T-Cell Co-Stimulatory Receptor (ICOS) Agonist GSK3359609 (GSK609) with Platinum+5-FU Chemotherapy (5-FU/plat), with or without Pembrolizumab (PE), for the Treatment of Advanced Solid Tumors (abstract #6544; presenter, Massarelli E).

Advancing Immuno-Oncology Research in Endometrial Cancer
Dostarlimab is an investigational anti-programmed death-1 (PD-1) monoclonal antibody that has demonstrated clinically meaningful results in women with recurrent or advanced mismatch repair-deficient (dMMR) endometrial cancer who progressed on or after a platinum-based regimen. Dostarlimab continues to be evaluated as a monotherapy and in combination with other assets across solid tumours. A presentation of interest includes:

• ENGOT-EN6/NSGO-RUBY: A Phase III, Randomized, Double-blind, Multicentre Study of Dostarlimab + Carboplatin-paclitaxel Versus Placebo + Carboplatin-paclitaxel in Recurrent or Primary Advanced Endometrial Cancer (EC) (abstract #TPS6107; presenter, Mirza M).

Additional GSK presentations from our areas of cancer research can be found below.

Immuno-oncology

Synthetic Lethality

Cell Therapy

GSK in Oncology 
GSK is focused on maximising patient survival through transformational medicines. GSK's pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination. 

Indications and Important Safety Information for ZEJULA

Indications

ZEJULA is indicated:

• for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.
• for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
• for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either: 
• a deleterious or suspected deleterious BRCA mutation, or
• genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy.

Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA.

Important Safety Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 15 patients (0.8%) out of 1785 patients treated with ZEJULA monotherapy in clinical trials. The duration of therapy in patients who developed secondary MDS/cancer therapy-related AML varied from 0.5 months to 4.9 years. These patients had received prior chemotherapy with platinum agents and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA; 29%, 25%, and 20% of patients receiving ZEJULA in NOVA; and 28%, 27%, and 13% of patients receiving ZEJULA in QUADRA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA; 3%, 1%, and 2% of patients in NOVA; and 4%, 2%, and 1% of patients in QUADRA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients in QUADRA, with discontinuation occurring in <0.2% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Embryo-Fetal Toxicity and Lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

First-line Maintenance Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%) and increased ALT (29%).

Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in NOVA were nausea (74%), thrombocytopenia (61%), fatigue/asthenia (57%), anemia (50%), constipation (40%), vomiting (34%), neutropenia (30%), insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis (23%), rash (21%), hypertension (20%), dyspnea (20%), mucositis/stomatitis (20%), dizziness (18%), back pain (18%), dyspepsia (18%), leukopenia (17%), cough (16%), urinary tract infection (13%), anxiety (11%), dry mouth (10%), AST/ALT elevation (10%), dysgeusia (10%), palpitations (10%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

Treatment of Advanced HRD+ Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in QUADRA were nausea (67%), fatigue (56%), thrombocytopenia (52%), anemia (51%), vomiting (44%), constipation (36%), abdominal pain (34%), musculoskeletal pain (29%), decreased appetite (27%), dyspnea (22%), insomnia (21%), neutropenia (20%), headache (19%), diarrhea (17%), acute kidney injury (17%), urinary tract infection (15%), hypertension (14%), cough (13%), dizziness (11%), AST/ALT elevation (11%), blood alkaline phosphatase increased (11%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in QUADRA included: decreased hemoglobin (83%), increased glucose (66%), decreased platelets (60%), decreased lymphocytes (57%), decreased leukocytes (53%), decreased magnesium (46%), increased alkaline phosphatase (40%), increased gamma glutamyl transferase (40%), increased creatinine (36%), decreased sodium (34%), decreased neutrophils (34%), increased aspartate aminotransferase (29%), and decreased albumin (27%).

Please see accompanying Prescribing Information

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.

Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D "Risk Factors" in the company's Annual Report on Form 20-F for 2019 and any impacts of the COVID-19 pandemic.

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ⁱ NCI Drug Dictionary - Anti-BCMA Antibody-Drug Conjugate GSK2857916. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-bcma-antibody-drug-conjugate-gsk2857916. Accessed March 2019.
ⁱⁱ Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with GSK2857916 antibody–drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. The Lancet Oncology. 2018;19(12):1641-1653. doi:10.1016/s1470-2045(18)30576-x.

SOURCE GlaxoSmithKline plc