GSK to showcase scientific advances and progress in oncology at ASCO and EHA

For media and investors only

Issued: London, UK

GlaxoSmithKline (GSK) plc will present new data from key focus areas within its oncology portfolio at the upcoming 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (June 4-8) and the European Hematology Association (EHA) 2021 Virtual Congress (June 9-17).

GSK will showcase innovative approaches to oncology R&D and cutting-edge science at the upcoming ASCO and EHA meetings. The company will present new data on its approved therapies, BLENREP (belantamab mafodotin-blmf), JEMPERLI (dostarlimab-gxly) and ZEJULA (niraparib), as well as its investigational T cell receptor T-cell therapy (TCR-T) letetresgene autoleucel (lete-cel; GSK3377794) for solid tumors.

Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: “The data we will share at ASCO and EHA demonstrate the continued strengthening of our oncology R&D pipeline in our focus areas of immuno-oncology, cell therapy and synthetic lethality. We are committed to ensuring our three approved medicines – ZEJULA, BLENREP and JEMPERLI – help as many patients as possible while exploring novel approaches to expand treatment options for the millions of lives impacted by cancer each year.”

Continuing GSK’s momentum in immuno-oncology

JEMPERLI, a programmed death receptor-1 (PD-1) blocking antibody, received accelerated approval in the US in April 2021 for certain women with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test who have progressed on or following prior treatment with a platinum-containing regimen. In addition, last month JEMPERLI also received a conditional approval in the EU for the treatment of women with dMMR/microsatellite instability-high (MSI-H) endometrial cancer. Data from the registrational GARNET trial of JEMPERLI in multiple tumor types will be presented at ASCO, including an interim combined efficacy and safety analysis of the endometrial and pan-tumor cohorts (ASCO abstract #2564).

Additionally, GSK will present new data regarding the management of adverse events associated with BLENREP in relapsed/refractory multiple myeloma (ASCO abstract #8033; EHA abstracts #EP1026 and #PB1698). BLENREP is an anti-BCMA (B-cell maturation antigen) treatment that received accelerated and conditional approvals in the US and EU, respectively, for adult patients with relapsed/refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 antibody, a proteasome inhibitor and an immunomodulatory agent. 

Updates from GSK’s efforts in synthetic lethality

GSK will share data from combined analysis of three phase III studies in patients with BRCA mutated ovarian cancer, examining the efficacy of ZEJULA, as well as its safety profile (ASCO abstract #5518). This research adds to the understanding of the use of this poly (ADP-ribose) polymerase (PARP) inhibitor for maintenance treatment in ovarian cancer. GSK remains committed to fully exploring the potential of ZEJULA, with clinical trials underway evaluating it in ovarian cancer in combination with other therapies and in other solid tumors.

GSK’s latest research in oncology cell therapy

Lete-cel, GSK’s leading cell therapy asset, is a potential first-in-class TCR-T consisting of modified T cells designed to recognize the NY-ESO-1 antigen, which is present across multiple solid tumors, including synovial sarcoma and myxoid/round cell liposarcoma.[1] A presentation of note will include findings from an interim analysis on the safety and efficacy of lete-cel in myxoid/round cell liposarcoma (ASCO abstract #11521). With three programs currently in clinical development and an emerging pipeline of enhancement technologies and targets, cell therapy in solid tumors is a key pillar of GSK’s broader oncology strategy to help address unmet patient needs. 

The complete list of GSK sponsored abstracts accepted by ASCO and EHA for presentation/ publication from the company’s areas of cancer research is below.

 

ASCO

Immuno-oncology

Abstract Name	Presenter	Abstract Number
Antitumor activity of dostarlimab in patients with mismatch mutation repair-deficient/microsatellite instability-high tumours: A combined analysis of 2 cohorts in the GARNET study	Berton, D.	#2564
Inducible T-cell co-stimulatory (ICOS) receptor agonist, feladilimab (fela), alone and in combination (combo) with pembrolizumab (P): Results from INDUCE-1 urothelial carcinoma (UC) expansion cohorts (ECs)	Balar, A.	#4519
Evaluation of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer: Data from phase 1 and phase 2 studies	Strauss, J.	#5509
Long-term follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck (SCCHN)	Chul Cho, B.	#6020
Relationship between corneal exam findings, best-corrected visual acuity (BCVA), and ocular symptoms in patients with relapsed or refractory multiple myeloma (RRMM) receiving belantamab mafodotin (belamaf)	Terpos, E.	#8033
Evolution of standard of care therapies used for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): A real-world analysis of patient health records from 2016 to 2019	Saba, N.F.	#e18728
Landscape review of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in oncology: Adoption and recent learnings	Regnault, A.	# e18587
Real-world treatment patterns and outcomes of triple-exposed multiple myeloma patients treated in community oncology practices in the United States	Smith, R.	#e18727
Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States	Maiese, E.M.	#e18693

 

Synthetic Lethality

Abstract Name	Presenter	Presentation Details
Niraparib efficacy and safety in patients with BRCA mutated (BRCAm) ovarian cancer: Results from three phase 3 niraparib trials	Gonzalez-Martin, A.	#5518
Real-world patterns and predictors of first-line maintenance use among newly diagnosed advanced ovarian cancer: Is there an opportunity for change?	Liu, J.	#e18710
Real-world progression free survival among newly diagnosed advanced ovarian cancer: Does maintenance therapy work?	Liu, J.	#e18707
Tissue distribution and brain penetration of niraparib in tumour bearing mouse models and its clinical relevance	Gada, K.	#e15066

 

Oncology Cell Therapy

Abstract Name	Presenter	Presentation Details
IGNYTE-ESO: A master protocol to assess safety and activity of letetresgene autoleucel (lete-cel; GSK3377794) in HLA-A*02+ patients with synovial sarcoma or myxoid/round cell liposarcoma (Substudies 1 and 2)	D’Angelo, S.	#TPS11582
Master protocol to assess safety and recommended phase 2 dose of next generation NY-ESO-1–specific TCR T-cells in HLA-A*02 patients with synovial sarcoma or non-small cell lung cancer (Substudies 1 and 2)	Schoenfeld, A.	#TPS2661
Safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794) in advanced myxoid/round cell liposarcoma (MRCLS) following high lymphodepletion (Cohort 2): Interim analysis	D’Angelo, S.	#11521

 

Cancer Epigenetics

Abstract Name	Presenter	Presentation Details
Real-world treatment patterns among advanced HR+/HER2- breast cancer patients in the post-CDK4/6 inhibitor era: An analysis of administrative claims data	Boyle, T. A.	#e18695

 

EHA

Immuno-oncology

Abstract Name	Presenter	Presentation Details
Characterization of ocular adverse events in patients receiving belantamab mafadotin for ≥12 months: post-hoc analysis of DREAMM-2 study in relapsed/refractory multiple myeloma	Lonial, S.	#EP1026
Relationship between corneal exam findings, best-corrected visual acuity (BCVA), and ocular symptoms in patients with relapsed or refractory multiple myeloma (RRMM) receiving belantamab mafodotin (belamaf)	Terpos, E.	#EP1001
DREAMM-5 platform trial: Belantamab mafodotin (belamaf) in combination with five different novel agents in patients with relapsed/refractory multiple myeloma (RRMM)	Richardson, P.	#PB1698
Landscape review of the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Oncology: Adoption and recent learnings	Regnault, A.	#EP1171

About BLENREP (belantamab mafodotin-blmf)
BLENREP is an antibody drug conjugate comprising a humanized anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seagen; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

INDICATION

BLENREP is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

 

IMPORTANT SAFETY INFORMATION

WARNING: OCULAR Toxicity BLENREP caused changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms such as blurred vision and dry eyes. Conduct ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms. Withhold BLENREP until improvement and resume, or permanently discontinue, based on severity. Because of the risk of ocular toxicity, BLENREP is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BLENREP REMS.

 

WARNINGS AND PRECAUTIONS

Ocular Toxicity: Ocular adverse reactions occurred in 77% of the 218 patients in the pooled safety population. Ocular adverse reactions included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%). Among patients with keratopathy (n = 165), 49% had ocular symptoms, 65% had clinically relevant visual acuity changes (decline of 2 or more lines on Snellen Visual Acuity in any eye), and 34% had both ocular symptoms and visual acuity changes.

Keratopathy: Keratopathy was reported as Grade 1 in 7% of patients, Grade 2 in 22%, Grade 3 in 45%, and Grade 4 in 0.5% per the KVA scale. Cases of corneal ulcer (ulcerative and infective keratitis) have been reported. Most keratopathy events developed within the first 2 treatment cycles (cumulative incidence of 65% by Cycle 2). Of the patients with Grade 2 to 4 keratopathy (n = 149), 39% recovered to Grade 1 or lower after median follow-up of 6.2 months. Of the 61% who had ongoing keratopathy, 28% were still on treatment, 9% were in follow-up, and in 24% the follow-up ended due to death, study withdrawal, or lost to follow-up. For patients in whom events resolved, the median time to resolution was 2 months (range: 11 days to 8.3 months).

Visual Acuity Changes: A clinically significant decrease in visual acuity of worse than 20/40 in the better-seeing eye was observed in 19% of the 218 patients and of 20/200 or worse in the better-seeing eye in 1.4%. Of the patients with decreased visual acuity of worse than 20/40, 88% resolved and the median time to resolution was 22 days (range: 7 days to 4.2 months). Of the patients with decreased visual acuity of 20/200 or worse, all resolved and the median duration was 22 days (range: 15 to 22 days).

Monitoring and Patient Instruction: Conduct ophthalmic examinations (visual acuity and slit lamp) at baseline, prior to each dose, and promptly for worsening symptoms. Perform baseline examinations within 3 weeks prior to the first dose. Perform each follow-up examination at least 1 week after the previous dose and within 2 weeks prior to the next dose. Withhold BLENREP until improvement and resume at same or reduced dose, or consider permanently discontinuing based on severity. Advise patients to use preservative-free lubricant eye drops at least 4 times a day starting with the first infusion and continuing until end of treatment. Avoid use of contact lenses unless directed by an ophthalmologist. Changes in visual acuity may be associated with difficulty for driving and reading. Advise patients to use caution when driving or operating machinery. BLENREP is only available through a restricted program under a REMS.

Thrombocytopenia: Thrombocytopenia occurred in 69% of 218 patients in the pooled safety population, including Grade 2 in 13%, Grade 3 in 10%, and Grade 4 in 17%. The median time to onset of the first thrombocytopenic event was 26.5 days. Thrombocytopenia resulted in dose reduction, dose interruption, or discontinuation in 9%, 2.8%, and 0.5% of patients, respectively. Grade 3 to 4 bleeding events occurred in 6% of patients, including Grade 4 in 1 patient. Fatal adverse reactions included cerebral hemorrhage in 2 patients. Perform complete blood cell counts at baseline and during treatment as clinically indicated. Consider withholding and/or reducing the dose based on severity.

Infusion-Related Reactions: Infusion-related reactions occurred in 18% of 218 patients in the pooled safety population, including Grade 3 in 1.8%. Monitor patients for infusion-related reactions. For Grade 2 or 3 reactions, interrupt the infusion and provide supportive treatment. Once symptoms resolve, resume at a lower infusion rate. Administer premedication for all subsequent infusions. Discontinue BLENREP for life-threatening infusion-related reactions and provide appropriate emergency care.

Embryo-Fetal Toxicity: Based on its mechanism of action, BLENREP can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with BLENREP and for 4 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with BLENREP and for 6 months after the last dose. Pregnancy testing is recommended for females of reproductive potential prior to initiating BLENREP.

ADVERSE REACTIONS

The pooled safety population described in Warnings and Precautions reflects exposure to BLENREP at a dosage of 2.5 mg/kg or 3.4 mg/kg (1.4 times the recommended dose) administered intravenously once every 3 weeks in 218 patients in DREAMM-2. Of these patients, 194 received a liquid formulation (not the approved dosage form) rather than the lyophilized powder.

Patients received BLENREP at the recommended dosage of 2.5 mg/kg administered intravenously once every 3 weeks (n = 95). Permanent discontinuation due to an adverse reaction occurred in 8% of patients who received BLENREP; keratopathy (2.1%) was the most frequent adverse reaction resulting in permanent discontinuation. Dosage interruptions due to an adverse reaction occurred in 54% of patients who received BLENREP. Adverse reactions which required a dosage interruption in >3% of patients included keratopathy (47%), blurred vision (5%), dry eye (3.2%), and pneumonia (3.2%). Dose reductions due to an adverse reaction occurred in 29% of patients. Adverse reactions which required a dose reduction in >3% of patients included keratopathy (23%) and thrombocytopenia (5%).

The most common adverse reactions (≥20%) were keratopathy (71%), decreased visual acuity (53%), nausea (24%), blurred vision (22%), pyrexia (22%), infusion-related reactions (21%), and fatigue (20%). The most common Grade 3 or 4 (≥5%) laboratory abnormalities were lymphocytes decreased (22%), platelets decreased (21%), hemoglobin decreased (18%), neutrophils decreased (9%), creatinine increased (5%), and gamma-glutamyl transferase increased (5%).

Serious adverse reactions occurred in 40% of patients who received BLENREP. Serious adverse reactions in >3% of patients included pneumonia (7%), pyrexia (6%), renal impairment (4.2%), sepsis (4.2%), hypercalcemia (4.2%), and infusion-related reactions (3.2%). Fatal adverse reactions occurred in 3.2% of patients, including sepsis (1%), cardiac arrest (1%), and lung infection (1%).

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with BLENREP and for 3 months after the last dose. 

Females and Males of Reproductive Potential: Based on findings in animal studies, BLENREP may impair fertility in females and males.

Geriatric Use: Of the 218 patients who received BLENREP in DREAMM-2, 43% were aged 65 to less than 75 years and 17% were aged 75 years and older. Keratopathy occurred in 80% of patients aged less than 65 years and 73% of patients aged 65 years and older. Among the 95 patients who received BLENREP at the 2.5-mg/kg dose, keratopathy occurred in 67% of patients aged less than 65 years and 73% of patients aged 65 years and older.

 

Renal or Hepatic Impairment: The recommended dosage has not been established in patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m²) or end-stage renal disease (ESRD) with eGFR <15 mL/min/1.73 m² not on dialysis or requiring dialysis. The recommended dosage has not been established in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN and any AST).

Please see full Prescribing Information, including BOXED WARNING and Medication Guide for BLENREP here.

About JEMPERLI (dostarlimab-gxly)

JEMPERLI is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.[2] In addition to GARNET, JEMPERLI is being investigated in other registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumors or metastatic cancers.

JEMPERLI was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: JEMPERLI (dostarlimab), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialization, and manufacturing of each of these Products under the Agreement.

INDICATION

• JEMPERLI is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen.
• This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Immune-Mediated Adverse Reactions

• Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI.
• Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
• Based on the severity of the adverse reaction, withhold or permanently discontinue JEMPERLI. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to ≤Grade 1. Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids.

 

Immune-Mediated Pneumonitis

• JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. The incidence of pneumonitis may be increased in patients who have received prior thoracic radiation. Pneumonitis occurred in 1.1% (5/444) of patients, including Grade 2 (0.9%) and Grade 3 (0.2%) pneumonitis.

 

Immune-Mediated Colitis

• Colitis occurred in 1.4% (6/444) of patients, including Grade 3 (0.7%) and Grade 2 (0.7%) adverse reactions. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies.

Immune-Mediated Hepatitis

• JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.2% (1/444) of patients.

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency
  • Adrenal insufficiency occurred in 0.9% (4/444) of patients, including Grade 3 (0.5%) and Grade 2 (0.5%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold JEMPERLI if not clinically stable.
• Hypophysitis
  • JEMPERLI can cause immune-mediated hypophysitis. Initiate hormone replacement as clinically indicated. Withhold JEMPERLI if not clinically stable.
• Thyroid Disorders
  • Thyroiditis occurred in 0.5% (2/444) of patients; both were Grade 2. Hypothyroidism occurred in 5.6% (25/444) of patients, all of which were Grade 2. Hyperthyroidism occurred in 1.8% (8/444) of patients, including Grade 2 (1.6%) and Grade 3 (0.2%). Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold JEMPERLI if not clinically stable.
• Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis
  • JEMPERLI can cause type 1 diabetes mellitus which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.

Immune-Mediated Nephritis with Renal Dysfunction

• JEMPERLI can cause immune-mediated nephritis, which can be fatal. Nephritis occurred in 0.5% (2/444) of patients; both were Grade 2.

Immune-Mediated Dermatologic Adverse Reactions

• JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity.

Other Immune-Mediated Adverse Reactions

• The following clinically significant immune-mediated adverse reactions occurred in <1% of the 444 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.
  • Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy
  • Cardiac/Vascular: Myocarditis, pericarditis, vasculitis
  • Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur.
  • Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis
  • Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica
  • Endocrine: Hypoparathyroidism
  • Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection

Infusion-Related Reactions

• Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/444) of patients receiving JEMPERLI. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue JEMPERLI based on severity of reaction.

Complications of Allogeneic HSCT after PD-1/PD-L1–Blocking Antibody:

• Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with a PD-1/PD-L1–blocking antibody, which may occur despite intervening therapy. Monitor patients closely for transplant-related complications and intervene promptly.

Embryo-Fetal Toxicity and Lactation:

• Based on its mechanism of action, JEMPERLI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after their last dose. Because of the potential for serious adverse reactions from JEMPERLI in a breastfed child, advise women not to breastfeed during treatment with JEMPERLI and for 4 months after their last dose.

Common Adverse Reactions

The most common adverse reactions (≥20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation.

Please see full Prescribing Information for JEMPERLI here.

About ZEJULA (niraparib)

ZEJULA is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development program by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes several combination studies.

INDICATION

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 FOR ZEJULA

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, neutropenia, and/or pancytopenia) 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 with ZEJULA. 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.

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports. Monitor all patients for signs and symptoms of PRES, which include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. Diagnosis requires confirmation by brain imaging. If suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA is unknown.

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.

Allergic reactions to FD&C Yellow No. 5 (tartrazine): ZEJULA capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

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 full Prescribing Information for ZEJULA here.

GSK in Oncology 

GSK is focused on maximizing 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 utilizing modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.

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.us.gsk.com/en-us/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 in the Company's Annual Report on Form 20-F for 2020 and any impacts of the COVID-19 pandemic.

References

[1] Thomas R,  Al-Khadairi G, Roelands J, et al. “NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives.” Frontiers in Immunology, Frontiers Media S.A., 1 May 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5941317/.

[2] Laken H, Kehry M, Mcneeley P, et al. Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of Cancer. 2016;69,S102. doi:10.1016/s0959-8049(16)32902-1.