GSK unveils latest research advances demonstrating strength of its portfolio and pipeline at ASCO and EHA

Issued: London UK

GSK plc will present 25 abstracts at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (3-7 June) and nine abstracts at the European Hematology Association (EHA) 2022 Hybrid Congress (9-12 June) focusing on approved therapies, Blenrep (belantamab mafodotin-blmf), Jemperli (dostarlimab-gxly) and Zejula (niraparib), as well as its investigational medicines. The data presentations further demonstrate the company’s commitment to evaluate its approved and investigational therapies alone and in combination with other treatments and explore potential opportunities to improve patient care.

Hesham Abdullah, SVP, Global Head of Oncology Development, GSK said: “We have strategically built a portfolio and pipeline that leverages the science of the immune system, human genetics and advanced technologies to address a variety of tumor types. The data we will be sharing at ASCO and EHA demonstrate how we’re delivering on our commitment to patients through novel approaches in some of the most promising areas of oncology research. We look forward to these important opportunities to come together and to share meaningful scientific updates with the broader oncology community.”

Updates from the robust DREAMM clinical trial program

Key presentations at ASCO and EHA include updates from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial program evaluating belantamab mafodotin-blmf, an anti-BCMA (B-cell maturation antigen) therapy, in combination with both standard of care and investigational agents in earlier lines of therapy. Preliminary data from DREAMM-5 sub-study 3 of low-dose belantamab mafodotin-blmf in combination with nirogacestat in patients with relapsed/refractory multiple myeloma (ASCO abstract #8019) will be reported. Nirogacestat, an investigational gamma secretase inhibitor, has been shown to increase target density and reduce levels of soluble BCMA, and as such the potential to enhance the activity of BCMA-targeted therapies like belantamab mafodotin-blmf is under investigation.

DREAMM-6 updates report outcomes from several dose cohorts of belantamab mafodotin-blmf in combination with lenalidomide and dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma who have received one or more prior lines of treatment (ASCO abstract #8017).

DREAMM-9, evaluating a quadruplet combination treatment regimen of belantamab mafodotin-blmf with standard of care (bortezomib, lenalidomide and dexamethasone or VRd) in patients with newly diagnosed multiple myeloma who are transplant ineligible, will also be presented at EHA (EHA abstract #P942).

Collectively, the data from these trials are evaluating the efficacy and safety of belantamab mafodotin-blmf in patients with various lines of therapy, but also aim to assess how dose, scheduling and combination treatment may help to reduce corneal events associated with treatment. These data will be used to help inform further studies evaluating the potential of belantamab mafodotin-blmf in the multiple myeloma setting.

Blenrep 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. Studies are ongoing to verify clinical benefit.

Advancing research for patients with mismatch repair-deficient solid cancers

Results from the GARNET trial Cohorts A1 and A2 of dostarlimab-gxly, a programmed cell death receptor-1 (PD-1) blocking antibody, in advanced/recurrent (A/R) mismatch repair deficient/microsatellite instability-high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer will be presented during a presentation at ASCO (ASCO abstract #5509). These results include the largest cohort of patients with dMMR A/R endometrial cancer treated with a PD-1 inhibitor monotherapy and will inform long-term use of dostarlimab-gxly in this patient population. In addition, long-term outcomes from the GARNET trial Cohorts A1 and F will be shared, covering the efficacy and safety profile of dostarlimab-gxly in certain patients with dMMR recurrent or advanced solid tumours, including endometrial cancer (ASCO abstract #2587). Results from Cohort A1 of the GARNET trial served as the basis for conditional approval in the EU for the treatment of certain patients with dMMR/MSI-H recurrent or advanced endometrial cancer, and for the accelerated approval in the US for certain patients with dMMR recurrent or advanced endometrial cancer. Additionally, results from Cohorts A1 and F served as the basis for the accelerated approval in the US for certain patients with dMMR recurrent or advanced solid tumors.

Realizing the potential of synthetic lethality

GSK will also present real-world analyses from six studies in patients with advanced ovarian cancer at ASCO, including real-world data evaluating outcomes in patients with advanced ovarian cancer who receive poly (ADP-ribose) polymerase (PARP) inhibitor monotherapy as maintenance compared to those who do not. Insights from the presentations will deepen the understanding of the use of PARP inhibitors for maintenance therapy in advanced ovarian cancer and shed light on differences in treatment practice across geographic locations.

Separately, a phase III PRIME study update will be shared by Zai Lab (a GSK partner) evaluating niraparib (independently manufactured by Zai Lab) in Chinese patients with newly diagnosed advanced ovarian cancer using an individualised starting dose in a poster presentation (ASCO abstract #5551).

Continued research on immuno-oncology investigational agents

GSK will also present findings from its early-stage pipeline assets, including an poster discussion on the AMBER study evaluating cobolimab, an investigational anti-TIM-3 targeting monoclonal antibody, in combination with dostarlimab-gxly in patients with advanced or metastatic melanoma (ASCO abstract #9513). TIM-3 is a key immune checkpoint and a novel immuno-oncology target that could play a critical role in the treatment of solid tumours. GSK is evaluating cobolimab for patients with different tumour types through various novel combinations, including doublets and triplets.

Collaborating to improve patient care  

GSK is supporting investigator-sponsored studies and fostering scientific collaborations with both experienced investigators and networks, who are involved in the continuum of care of patients living with cancer. At ASCO, updated data from an investigator-sponsored study from Memorial Sloan Kettering Cancer Center will be featured in a late-breaking oral presentation entitled, “Single Agent PD-1 Blockade as Curative-Intent Treatment in Mismatch Repair Deficient Locally Advanced Rectal Cancer” (ASCO abstract #LBA5).  Initial data were presented earlier this year at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). There will be five additional GSK-supported investigator-sponsored studies presented at ASCO. 

At EHA, data from the BelaCarD investigator-sponsored study will report safety, tolerability and preliminary efficacy of belantamab mafodotin-blmf in combination with carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma (EHA abstract #P946). Additionally, an oral presentation on updated results from a supported collaborative study will evaluate the safety and efficacy of belantamab mafodotin-blmf plus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma (EHA abstract #S178).

Full list of GSK’s presentations at ASCO:

Dostarlimab

Belantamab mafodotin

Niraparib

Pipeline

Full list of investigator-sponsored studies at ASCO:

Full list of GSK’s presentations at EHA:

Full list of investigator-sponsored studies at EHA:

Making our products affordable and accessible

GSK is actively involved in creating solutions that allow patients to have access to new scientific breakthroughs. We remain committed to helping patients access GSK medications and have a long history of providing patient assistance programs. Patients and healthcare professionals can access more information about our oncology specific resources on insurance coverage and financial support at: www.TogetherwithGSKOncology.com or call: 1-844-4GSK-ONC (1-844-447-5662).

About multiple myeloma

Multiple myeloma is the second most common blood cancer in the US and is generally considered treatable, but not curable. In the US, more than 32,000 people are estimated to be diagnosed with multiple myeloma this year and nearly 13,000 people will die from the disease. Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.

About endometrial cancer

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. It is the most common gynaecologic cancer in the US and second most common gynaecologic cancer globally. Approximately 15-20% of women with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.

About ovarian cancer

Ovarian cancer is the 8th most common cancer in women worldwide. Despite high response rates to platinum-based chemotherapy in the front-line setting, approximately 85% of patients will experience disease recurrence. Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence.

Indication and Important Safety Information for BLENREP (belantamab mafodotin-blmf)

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

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%).

Clinically relevant adverse reactions from expanded access programs include: pneumonitis including fatal cases.  

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.

About dostarlimab-gxly

Dostarlimab-gxly 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. In addition to GARNET, dostarlimab-gxly 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 tumours or metastatic cancers.

Dostarlimab-gxly 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: dostarlimab-gxly (GSK4057190), a PD-1 antagonist; cobolimab (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these assets under the Agreement.

Indications and Important Safety Information for JEMPERLI (dostarlimab-gxly)

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, or
• solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

These indications are approved under accelerated approval based on tumor response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

Severe and Fatal 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. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Pneumonitis occurred in 1.4% (7/515) of patients, including Grade 2 (1.2%) and Grade 3 (0.2%) pneumonitis.

Immune-Mediated Colitis

• Colitis occurred in 1.4% (7/515) of patients, including Grade 2 (0.8%) and Grade 3 (0.6%) 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% (1/515) of patients.

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency
  • Adrenal insufficiency occurred in 1.4% (7/515) of patients, including Grade 2 (0.8%) and Grade 3 (0.6%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
• Hypophysitis
  • JEMPERLI can cause immune-mediated hypophysitis. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
• Thyroid Disorders
  • Thyroiditis occurred in 0.4% (2/515) of patients; both were Grade 2. Hypothyroidism occurred in 7.2% (37/515) of patients, all of which were Grade 2. Hyperthyroidism occurred in 1.9% (10/515) of patients, including Grade 2 (1.7%) and Grade 3 (0.2%). Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
• 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 0.4% (2/515) 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 515 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): Autoimmune 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% (1/515) 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

• 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%) in patients with dMMR EC were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, decreased leukocytes, decreased albumin, increased creatinine, increased alkaline phosphatase, and increased alanine aminotransferase.

Please see full Prescribing Information

About Niraparib

Niraparib 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 tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes several combination studies.

Indications and Important Safety Information for ZEJULA (niraparib)

 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, 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 not to 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

GSK in Oncology

GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, tumor cell targeting therapies 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. For further information please visit https://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 2021, GSK’s Q1 Results for 2022 and any impacts of the COVID-19 pandemic.

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