Oncology

Meet Us

NRG | Jan 9-11, 2020 | Houston, TX

SGO | Mar 28-31, 2020 | Toronto, Canada

ASCO | May 29-June 2, 2020 | Chicago,IL

IGCS | Sept 10-12, 2020 | Rome, Italy

ESMO | Sept 18-20, 2020 | Madrid, Spain

SITC | Nov 11-14, 2020 | Natl Harbor, MD

ASH | Dec 5-8, 2020 | San Diego, CA

ZEJULA

(niraparib)

Prescribing Information

Material Safety Data Sheets &
Environmental Risk Assessments

How Supplied/Storage & Handling

ZEJULA is available as capsules having a white body printed with “100 mg” in black ink, and a purple cap printed with “Niraparib” in white ink.
Each capsule contains 100 mg of niraparib free base.
ZEJULA capsules are packaged as
- 90-count bottles NDC 69656-103-90
- 30-count bottles NDC 69656-103-30
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Pipeline Assets

Immuno-Oncology

The growing understanding of tumor cells’ ability to evade immune surveillance has led to advanced in the field of immune-oncology.¹ Malignant cells manipulate a variety of physiological mechanisms involved in antigenicity, immune activation, T-cell priming and recruitment, and upregulation of checkpoint molecules.¹ Many of these mechanisms may be impacted simultaneously to promote tumor cell survival.¹ Immunotherapies harness the body’s own immune system to fight cancer by using different immunological pathways to enhance antitumor responses.^1,2 GSK is exploring different clinical assets aimed at augmenting the immune response, reducing immune suppression, and modulating the tumor microenvironment.^3,4

Immuno-Oncology	Phase I	Phase II	Phase III

DREAMM-9: Newly Diagnosed Mutiple Myeloma in Combination With Lenalidomide, Bortezomib, and Dexmaethasone			NCT04091126
DREAMM-2: Relapsed/Refractory Multiple Myeloma		NCT03525678
DREAMM-4: Relapsed/Refractory Multiple Myeloma in Combination With Pembrolizumab	NCT03848845
DREAMM-6: Relapsed/Refractory Multiple Myeloma in Combination With Lenalidomide Plus Dexamethasone or in Combination With Bortezomib Plus Dexamethasone	NCT03544281
Relapsed/Refractory Multiple Myeloma in Japanese Patients	NCT03828292

RUBY: Recurrent or Primary Advanced Endometrial Cancer in Combination With Chemotherapy			NCT03981796
GARNET: Microsatellite Instability High (MSI-H)Tumors (Including Metastatic Endometrial Cancer), Microsatellite Stable (MSS) Endometrial Cancer, and Non-Small Cell Lung Cancer (NSCLC)	NCT02715284
IOLite: Advanced NSCLC and Solid Tumors in Combination With Niraparib (PARP Inhibitor), TSR-022 (Anti-TIM-3 Antibody), Bevacizumab, and/or Platinum-Based Doublet Chemotherapy	NCT03307785

INDUCE-3: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) in Combination with Pembrolizumab		NCT04128696
ENTREE-Lung: Advanced NSCLC in Combination With Docetaxel		NCT03739710
INDUCE-2: Advanced Solid Tumors in Combination With Tremelimumab	NCT03693612
INDUCE-1: Advanced Solid Tumors Alone and in Combination With Pembrolizumab or Chemotherapy	NCT02723955

AMBER: Melanoma, NSCLC, and Colorectal Cancer Alone and in Combination With Dostarlimab (TSR-042, Anti-PD-1 Antibody)	NCT02817633

CITRINO: Advanced Solid Tumors Alone and in Combination With Dostarlimab	NCT03250832

Advanced Solid Tumors Alone and in Combination With Pembrolizumab	NCT03843359

INTR@PID BTC 055: First-Line Treatment With Gemcitabine and Cisplatin Alone or in Combination With Bintrafusp Alfa in Biliary Tract Cancer		NCT04066491
INTR@PID BTC 047: Locally Advanced or Metastatic Second Line Biliary Tract Cancer		NCT03833661
INTR@PID LUNG 037: First-Line Treatment in PD-L1-Expressing Advanced NSCLC		NCT03631706
INTR@PID LUNG 005: Unresectable Stage III NSCLC in Combination With Concurrent Chemoradiation Therapy		NCT03840902
INTR@PID LUNG 024: Stage IV NSCLC in Combination With Chemotherapy	NCT03840915
INTR@PID SOLID TUMOR 001: Locally Advanced or Metastatic Solid Tumors	NCT02517398
INTR@PID SOLID TUMOR 008: Locally Advanced or Metastatic Solid Tumors	NCT02699515

ENGAGE-1: Advanced Solid Tumors Alone and in Combination With Pembrolizumab	NCT02528357

Advanced Solid Tumors in Combination With GSK3174998 (OX40 Agonist), GSK3359609 (ICOS Agonist), or Pembrolizumab	NCT03447314

Advanced NY-ESO-1- and/or LAGE-1a-Positive NSCLC, Melanoma, Urothelial Carcinoma, and Synovial Sarcoma	NCT03515551

References:

Allard B, Aspeslagh S, Garaud S, et al. Immuno-oncology-101: overview of major concepts and translational perspectives. Semin Cancer Biol. 2018;52(pt 2):1-11.
PhRMA. Medicines in development for immuno-oncology 2017 report. https://www.phrma.org/medicines-in-development-immuno-oncology. Accessed January 30, 2019.
Tai Y-T, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7(11):1187-1199.
Knudson KM, Hicks KC, Luo X, Chen J-Q, Schlom J, Gameiro SR. M7824, a novel bifunctional anti-PD-L1/TGF trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine. Oncoimmunology. 2018;7(5):e1426519. doi:10.1080/2162402X.2018.1426519.

* In-license or other partnership with third party
^† Tesaro acquisition
^‡ Being developed in a strategic global alliance between GSK and Merck KgaA, Darmstadt, Germany
^‖ Option-based alliance with Immunocore Ltd. ImmTAC is a registered trademark of Immunocore Ltd.

Synthetic Lethality

Accumulation of DNA damage and genomic instability are pervasive characteristics of human tumors and are caused by defects in DNA repair.^1,2 Deficiencies in essential DNA damage repair in cancer cells may increase dependency on an alternate repair pathway for cell survival.² Synthetically lethal therapies aim to combine pharmacologic inhibtion Of these alternate repair pathways with inherent defects in DNA damage repair to selectively kill tumor cells while sparing healthy tissue.^3-4 GSK is investigating a clinical asset that utilizes the power of synthetically lethal interactions to fight malignant cells in a variety of cancers.

Synthetic Lethality	Phase I	Phase II	Phase III

PRIMA: Advanced Ovarian Cancer First-Line Maintenance Following Response to Front-Line Platinum-Based Chemotherapy			NCT02655016
FIRST^†: First-Line Ovarian Cancer Treatment in Combination With Platinum-Based Chemotherapy and Dostarlimab Followed by Maintenance With Niraparib in Combination With Dostarlimab			NCT03602859
OVARIO: Advanced Ovarian Cancer First-Line Maintenance in Combination With Bevacizumab Following Front-Line Platinum-Based Chemotherapy Plus Bevacizumab		NCT03326193
OPAL: Platinum-Resistant Ovarian Cancer Treatment (Second or Third Line) in Combination With Dostarlimab and Bevacizumab		NCT03574779
MOONSTONE: Platinum-Based Ovarian Cancer Treatment in Combination With Dostarlimab		NCT03955471
TOPACIO: Advanced or Metastatic Triple Negative Breast Cancer or Recurrent Ovarian Cancer in Combination with Pembrolizumab	NCT02657889
Neoadjuvant Treatment in HER2- and BRCA^mut Localized Breast Cancer	NCT03329937
Pharmacokinetics and Safety in Patients With Advanced Solid Tumors and Normal Hepatic Function or Moderate Hepatic Impairment		NCT03359850
Crossover Bioavailability Study of Niarparib Tablet Compared to Niraparib Capsule in Advanced Solid Tumors		NCT03329001

References:

Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481(7381):287-294.
O’Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60(4):547-560.
Kelley MR, Logsdon D, Fishel ML. Targeting DNA repair pathways for cancer treatment: what’s new? Future Oncol. 2014;10(7):1215-1237.
O'Neil NJ, Bailey ML, Hieter P. Synthetic lethality and cancer. Nat Rev Genet. 2017;18(10):613-623.

* Tesaro acquisition
^† In collaboration with ENGOT, the European Network for Gynaecological Oncological Trial groups

Cancer Epigenetics

Aberrant gene expression, regulated in large part by epigenetic mechanisms, is a hallmark of cancer.¹ “Epigenetics” refers to heritable changes in gene expression that arise from changes in chromosomes without altering the DNA sequence.² DNA methylation and posttranslational modifications of histones play key roles in regulating gene expression.^1,3 Deregulation of these epigenetic mechanisms can lead to aberrant expression of oncogenes and tumor suppressors in cancer cells that can enhance proliferative signals, impair cell death, promote angiogenesis, and facilitate metastasis. GSK is investigating compounds that work by altering these epigenetic pathways.

Cancer Epigenetics	Phase I	Phase II

Relapsed/Refractory Hematologic Malignancies	NCT01943851
HR+/HER2- Breast Cancer in Combination With Fulvestrant	NCT02964507
NUT Midline Carcinoma and Other Cancers	NCT01587703
Castration-Resistant Prostate Cancer (CRPC) in Combination With Androgen Deprivation Therapy and Other Agents	NCT03150056

Relapsed/Refractory Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)	NCT03614728
Solid Tumors and Non-Hodgkin's Lymphoma (NHL)	NCT02783300

Relapsed/Refractory Solid Tumors and Diffuse Large B-Cell Lymphoma (DLBCL)	NCT03666988

Metastatic Castration-Resistant Prostate Cancer (mCRPC) in Combination With Enzalutamide	NCT02215096

References:

Kanwal R, Gupta S. Epigenetic modifications in cancer. Clin Genet. 2012;81(4):303-311.
Nebbioso A, Tambaro FP, Dell’Aversana C, Altucci L. Cancer epigenetics: moving forward. PLoS Genet. 2018;14(6):e1007362.
Pérez-Salvia M, Esteller M. Bromodomain inhibitors and cancer therapy: from structures to applications. Epigenetics. 2017;12(5):323-339.

* In-license or other partnership with third party

Cell Therapy

The physiologic role of central and peripheral tolerance mechanisms is to limit unchecked immune responses that can lead to autoimmunity.¹ In cancer, these mechanisms are major limitations to effective T-cell mediated antitumor immunity.¹ Oncology cell therapy uses adoptive transfer Of engineered T cells that may mediate antitumor effects. In adoptive cell therapy, T cells are isolated from the patient, engineered to present an enhanced TCR that recognizes a specific antigen, and then reintroduced into the patient.^1,2 This innovative approach generates T cells that may be more efficient at targeting cancer cells and may overcome the barriers of tolerance mechanisms" GSK is developing an engineered TCR T-cell clinical asset designed to target a tumor-specific antigen and eliminate malignant cells in solid tumors and hematologic malignancies.

Oncology Cell Therapy	Phase I	Phase II

Master Protocol–Advanced NY-ESO-1– and/or LAGE-1a–Positive Synovial Sarcoma and Solid Tumors		NCT03967223
Relapsed/Refractory NY-ESO-1– and/or LAGE-1a–Positive Multiple Myeloma Alone and in Combination with Pembrolizumab		NCT03168438
Advanced Myxoid/Round Cell Liposarcoma		NCT02992743
Advanced NY-ESO-1– and/or LAGE-1a–Positive NSCLC Alone and in Combination with Pembrolizumab	NCT03709706
Unresectable, Metastatic, or Recurrent HLA-A*02+ Synovial Sarcoma	NCT01343043
NY-ESO-1– and/or LAGE-1a–Positive Advanced NSCLC	NCT02588612
Long-Term Follow-up from Previous GSK3377794 Studies	NCT03391778

References:

Perica K, Varela JC, Oelke M, Schneck J. Adoptive T cell immunotherapy for cancer. Rambam Maimonides Med J. 2015;6(1):e0004.
Sharpe M, Mount N. Genetically modified T cells in cancer therapy: opportunities and challenges. Dis Model Mech. 2015;8(4):337-350.