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[JEMPERLI logo]
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[JEMPERLI logo]
Learn More About the RUBY Trial Results for JEMPERLI (dostarlimab-gxly)
For US Healthcare Professionals
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[JEMPERLI logo]
Please see IMPORTANT SAFETY INFORMATION throughout this video and full Prescribing Information at the adjacent links or JEMPERLIHCP.com
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DR. CECELIA H. BOARDMAN, MD
GYNECOLOGIC ONCOLOGIST, SARAH CANNON CANCER NETWORK
AT HENRICO DOCTORS' HOSPITAL, RICHMOND, VA
Paid consultant to GSK at the time of filming.
CECELIA BOARDMAN:
Hello. My name is Dr. Cecelia Boardman, and I am a board-certified gynecologic oncologist with Virginia Gynecologic Oncology, which is part of the Sarah Cannon Cancer Network at Henrico Doctors’ Hospital.
On behalf of GSK and myself, thank you for your time and attention.
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Main Topics Covered
Unmet Need in Primary Advanced/Recurrent Endometrial Cancer
Importance of dMMR/MSI-H Biomarkers in Endometrial Cancer
RUBY Clinical Trial Results
CECELIA BOARDMAN:
Today, I will discuss how JEMPERLI in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, may be an appropriate treatment for certain patients with primary advanced or recurrent endometrial cancer. Specifically, I will review: the unmet need in the treatment of primary advanced or recurrent endometrial cancer; the importance of biomarkers in endometrial cancer, specifically dMMR and MSI-high, with regards to immunotherapy; and lastly, the use of JEMPERLI in combination with carboplatin and paclitaxel in the treatment of dMMR or MSI-high primary advanced or recurrent endometrial cancer as investigated in the RUBY clinical trial.
Please remember any opinions expressed in this video are my own and I am speaking from my own clinical experience about prescribing JEMPERLI to appropriate patients. This may not be reflective of the experiences from all healthcare providers.
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INDICATION
JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
Let’s start by reviewing JEMPERLI’s indication based on the RUBY trial, and some Important Safety Information.
JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient, also known as dMMR, as determined by an FDA-approved test, or microsatellite instability-high, also known as MSI-high.
Now, let’s hear some Important Safety Information.
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IMPORTANT SAFETY INFORMATION:
Severe and Fatal Immune-Mediated Adverse Reactions
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.
PD-1, programmed death receptor-1; PD-L1, programmed death ligand-1.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
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, such as 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 per kg per day prednisone or equivalent) until improvement to less than or equal to Grade 1. Upon improvement to less than or equal 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.
Additional safety information will be reviewed later in this video.
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Incidence of Endometrial Cancer in the US
[Graphic] In 20231:
>59,000 new diagnoses
>11,000 deaths
[Bar graph; Percentage versus Stage] 5-Year Relative Survival Rate and Percentage of Cases by Stage at Diagnosis in Uterine Cancer2*
5-year relative survival rate; Cases by stage at diagnosis
Localized; 94.9%; 67%
Regional; 69.8%; 19%
Distant; 18.4%; 10%
Although most patients are diagnosed with localized disease, those with advanced disease typically have a poor prognosis2
* SEER 22 (Excluding IL/MA) 2013–2019, All Races, Females by SEER Combined Summary Stage.
SEER, Surveillance, Epidemiology, and End Results Program.
1. American Cancer Society. Cancer Facts & Figures 2023. American Cancer Society; 2023. 2. National Cancer Institute. SEER cancer stat facts: uterine cancer. Accessed January 22, 2024. https://seer.cancer.gov/statfacts/html/corp.html
CECELIA BOARDMAN:
Let’s turn our attention to endometrial cancer. Endometrial cancer originates in the endometrium of the uterus and represents over 90% of all uterine corpus malignancies. Endometrial cancer is the most common gynecologic cancer, affecting more than 59,000 new patients per year in the United States. In 2023, it is estimated that more than 11,000 patients with endometrial cancer will die in the United States.
The bar graph shows data for uterine cancer based on disease stage. The blue bars indicate 5-year relative survival rate while the grey bars correlate to the percentage of cases at diagnosis. Although most patients are diagnosed with localized disease, those with advanced endometrial cancer typically have a poor prognosis.
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Unmet Need in Primary Advanced or Recurrent Endometrial Cancer
[Graphic] For >10 years, chemotherapy (i.e., carboplatin + paclitaxel) has been the standard of care for systemic treatment in patients with primary advanced or recurrent endometrial cancer, but mPFS is ~1 year1,2
Treatment(s) can include3:
Surgery
Radiation therapy
Systemic therapy
mPFS, median progression-free survival.
1. Miller DA, et al. J Clin Oncol. 2020;38(33):3841–3850. 2. Miller D, et al. Gynecol Oncol. 2012;125:771–773. 3. National Cancer Institute. Endometrial cancer treatment (PDQ®)–health professional version. Updated March 13, 2023. Accessed June 12, 2023. https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq#section/all
CECELIA BOARDMAN:
For the last decade, chemotherapy, specifically carboplatin plus paclitaxel, has been the standard of care for systemic treatment in patients with primary advanced or recurrent endometrial cancer, but the median progression-free survival is only approximately 1 year. Typical treatments for primary advanced or recurrent endometrial cancer can include surgery, systemic therapy, radiation therapy, or a combination.
One of the biggest challenges in treating patients with this type of endometrial cancer is when the disease returns quickly, although initial chemotherapy has good response rates. Personally, I have been very excited for treatment options for certain patients that may offer them a higher likelihood of response and longer duration of response.
Moreover, biomarker testing and classification can help guide tumor characterization and the most appropriate treatment plan for patients.
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dMMR/MSI-H in Endometrial Cancer
Endometrial cancer has the highest rate of dMMR across tumor types1
[Graphic] ~25–30% of endometrial tumors are dMMR/MSI-H2,3
MMR/MSI testing is recommended for all patients with primary advanced or recurrent endometrial cancer4
dMMR, mismatch repair deficient; MMR, mismatch repair; MSI-H, microsatellite instability-high.
1. Le DT, et al. Science. 2017;357(6349):409–413. 2. Makker V, et al. Nat Rev Dis Primers. 2021;7(1):88. 3. Lorenzi M, et al. J Oncol. 2020;1–17. 4. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. Published March 1, 2014. Accessed January 22, 2024. https://www.sgo.org/resources/screening-for-lynch-syndrome-in-endometrial-cancer/
CECELIA BOARDMAN:
dMMR/MSI-high is a commonly identified biomarker in endometrial cancer. Endometrial cancer has the highest rate of dMMR across tumor types. Approximately 25 to 30% of endometrial cancers are dMMR or MSI-high. These types of cancers often have high mutation rates, leading to the production of altered proteins and neoantigens. That is why MMR/MSI testing is recommended for all patients with primary advanced or recurrent endometrial cancer.
In my institution, our pathology laboratory tests all endometrial cancers for dMMR/MSI-high at diagnosis, so we have that information in time to make informed treatment decisions.
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Patients With Primary Advanced or Recurrent dMMR/MSI-H Endometrial Cancer May Benefit
From Immunotherapy1
Testing for dMMR/MSI-H helps identify patients with primary advanced or recurrent endometrial cancer who may be appropriate candidates for anti–PD-1 therapies, like JEMPERLI2,3
dMMR/MSI-H tumors are more likely to respond to anti-PD-1 therapies due to increased mutations that promote antitumor immune cell reaction and increased tumor-infiltrating lymphocytes
dMMR, mismatch repair deficient; MSI-H, microsatellite instability-high; PD-1, programmed death receptor-1.
1. Makker V, et al. Nat Rev Dis Primers. 2021;7(1):88. 2. Le DT, et al. N Engl J Med. 2015;372(26):2509–2520. 3. JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
Certain patients with primary advanced or recurrent endometrial cancer can be ideal candidates for immunotherapy. Endometrial cancer subtypes with dMMR/MSI-high can be associated with high mutation rates, promoting antitumor immune cell reaction and increased tumor-infiltrating lymphocytes. As a result of the high mutation rate and immunogenicity of these tumors, dMMR/MSI-high functions as a predictive biomarker for immunotherapy eligibility, and that is why dMMR/MSI-high tumors are more likely to respond to anti–PD-1 therapies. PD-1 inhibitors, including JEMPERLI, are currently FDA-approved for the treatment of certain types of endometrial cancer.
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Immune Checkpoint Inhibitors in Combination With Chemotherapy (i.e., carboplatin and paclitaxel) May Improve Treatment Response in Certain Patients1,2
[Graphic] Immune Checkpoint Inhibitors3
Tumor cells; ICIs
Due to increased mutations that promote antitumor immune cell reaction and increased tumor-infiltrating lymphocytes, dMMR/MSI-H tumors are more likely to respond to anti–PD-1 therapies
[Graphic] ICIs + Chemotherapy
[Graphic] Chemotherapy1
T cells; Tumor cells
Cytotoxic chemotherapy promotes antitumor immunity by inducing immunogenic cell death, which increases intratumoral T-cell infiltration6
dMMR, mismatch repair deficient; ICI, immune checkpoint inhibitor; MSI-H, microsatellite instability-high; PD-1, programmed death receptor-1.
1. Li JY, et al. Molec Cancer. 2021;20(27):1–21. 2. Mirza MR, et al. N Engl J Med. 2023;388(23):2145–2158. 3. Le DT, et al. N Engl J Med. 2015;372:2509–2520.
CECELIA BOARDMAN:
While immune checkpoint inhibitors, such as PD-1 inhibitors, have shown efficacy in treating certain types of endometrial cancer, combining them with chemotherapy, specifically carboplatin and paclitaxel, may improve treatment response in certain patients.
Some platinum-based chemotherapies have been identified to induce immunogenic cell death instead of inducing apoptosis and necrosis of cancer cells. This means that some cytotoxic chemotherapy can promote a long-lasting antitumor immunity by increasing intratumoral T-cell infiltration. PD-1 inhibitors bind to the PD-1 receptors on T cells to effectively block PD-L1 and PD-L2 interactions on the surface of the tumor. By adding chemotherapy, it allows for greater T-cell infiltration within the tumor, enabling for more effective delivery of the checkpoint inhibitor and for the T cells to then identify and kill cancer cells.
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The RUBY Trial Had a Major Efficacy Outcome of PFS* With Additional Efficacy Outcomes of OS, ORR, and DOR in the dMMR/MSI-H EC Subgroup1
RUBY was a randomized, multicenter, double-blind, placebo-controlled trial1
[Graphic] Patient Population1 Overall patient population (N=494)2† was randomized 1:1; dMMR/MSI-H subgroup (n=122)
JEMPERLI 500 mg, carboplatin AUC 5 mg/mL/min, paclitaxel 175 mg/m2 IV Q3W for 6 doses‡ (n=60); JEMPERLI 1000 mg IV, Q6W for up to 3 years
Placebo, carboplatin AUC 5 mg/mL/min, paclitaxel 175 mg/m2 IV Q3W for 6 doses (n=62);
Placebo IV, Q6W for up to 3 years
Follow-Up Median efficacy follow-up was 25 months2
Randomization was stratified by MMR/MSI status, prior external pelvic radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV).1
* Assessed by the investigator according to RECIST v1.1.1 † In RUBY, 494 patients underwent randomization to each treatment arm.2 The safety profile was evaluated in the 241 patients who were randomized to JEMPERLI + CP with primary advanced or recurrent EC. The safety data presented in the RUBY safety tables of this video reflects exposure to JEMPERLI in 52 patients with dMMR/MSI-H primary advanced or recurrent EC.1 ‡ JEMPERLI was administered prior to chemotherapy on Day 1 of each 21-day cycle. Treatment with JEMPERLI continued until disease progression, unacceptable toxicity, or a maximum of 3 years.1
AUC, area under the curve; CP, carboplatin-paclitaxel; dMMR, mismatch repair deficient; DOR, duration of response; EC, endometrial cancer; IV, intravenous; MMR, mismatch repair; MSI, microsatellite instability; MSI-H, microsatellite instability-high; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks; Q6W, every 6 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.
1. JEMPERLI. Prescribing Information. GSK; 2024. 2. Mirza MR, et al. N Engl J Med. 2023;388(23):2145–2158.
CECELIA BOARDMAN:
The RUBY clinical trial investigated the efficacy and safety of JEMPERLI in combination with carboplatin and paclitaxel, which I will occasionally refer to as chemotherapy from here on, followed by JEMPERLI as a single agent, in patients with dMMR/MSI-high primary advanced or recurrent endometrial cancer. RUBY was a randomized, multicenter, double-blind, placebo-controlled clinical trial, with a median efficacy follow-up of 25 months. Patients in the study had primary FIGO Stage III or Stage IV disease, or first recurrent endometrial cancer with a low potential for cure by radiation therapy or surgery alone or in combination treatment.
The randomization was stratified by MMR/MSI status, prior external pelvic radiotherapy, and disease status. Patients were randomized one-to-one into two treatment arms: the experimental group received 500 mg of JEMPERLI plus carboplatin and paclitaxel every 3 weeks for 6 doses, followed by 1000 mg of JEMPERLI monotherapy every 6 weeks beginning with dose 7. The control group received placebo plus carboplatin and paclitaxel every 3 weeks for 6 doses, followed by placebo every 6 weeks beginning with dose 7. Treatment with JEMPERLI continued until disease progression, unacceptable toxicity, or a maximum of 3 years.
Efficacy was assessed in a pre-specified subgroup of 122 patients with dMMR/MSI-high primary advanced or recurrent endometrial cancer. For this subgroup, the major efficacy outcome was progression-free survival by investigator assessment according to RECIST v1.1, and the additional efficacy outcomes were overall survival, objective response rate, and duration of response.
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In the dMMR/MSI-H Endometrial Cancer JEMPERLI + CP Arm: Groundbreaking 71% Reduction in the Risk of Progression or Death vs CP Alone1
[Line Graph; PFS Probability versus Months Since Randomization] Superior PFS* With JEMPERLI + CP vs CP alone in the dMMR/MSI-H primary advanced or recurrent endometrial cancer subgroup (n=122)1
JEMPERLI + CP (n=60); Placebo + CP (n=62)
HR=0.29; (95% CI: 0.17–0.50)†; P<0.0001‡
[Table] # at Risk
JEMPERLI + CP; 60; 55; 52; 43; 38; 34; 32; 31; 30; 28; 26; 20; 14; 10; 10; 5; 1; 0
Placebo + CP; 62; 54; 51; 34; 25; 13; 11; 11; 9; 6; 6; 5; 3; 2; 2; 1; 0
[Graphic] Median PFS‡1
30.3 months with JEMPERLI + CP (95% CI: 11.8–NR)
7.7 months with Placebo + CP (95% CI: 5.6–9.7)
Overall survival data in the dMMR/MSI-H subgroup were immature with 27% deaths1§
- HR=0.29 (95% CI: 0.13–0.64)3†
- OS was a prespecified exploratory analysis in the dMMR/MSI-H subgroup with no planned hypothesis testing, and no conclusions can be drawn from this analysis2
- OS continues to be evaluated in the dMMR/MSI-H subgroup2
* PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by investigator.1 † Based on stratified Cox regression model.1 ‡ One-sided p-value based on stratified log-rank test was statistically significant.1 § OS in the dMMR/MSI-H subgroup was not powered to demonstrate statistically significant differences.2
CI, confidence interval; CP, carboplatin-paclitaxel; dMMR, mismatch repair deficient; EC, endometrial cancer; HR, hazard ratio; MSI-H, microsatellite instability-high; NR, not reached; PFS, progression-free survival.
1. JEMPERLI. Prescribing Information. GSK; 2024. 2. Mirza MR, et al. N Engl J Med. 2023;388(23):2145–2158. 3. Data on file, GSK.
CECELIA BOARDMAN:
JEMPERLI in combination with chemotherapy demonstrated a durable progression-free survival benefit compared to chemotherapy alone in patients with dMMR or MSI-high primary advanced or recurrent endometrial cancer. The median PFS was 30.3 months with JEMPERLI plus chemotherapy, compared to 7.7 months for chemotherapy alone. PFS data had a hazard ratio of 0.29, which means a groundbreaking 71% reduction in the risk of progression or death was seen with JEMPERLI plus chemotherapy versus chemotherapy alone.
Overall survival, or OS, was an additional efficacy outcome that was evaluated in the dMMR/MSI-high subgroup. OS data in this subgroup were immature with 27% deaths, and a hazard ratio of 0.29. In the dMMR/MSI-high subgroup, OS was not powered to demonstrate statistically significant differences. It was a prespecified exploratory analysis with no planned hypothesis testing and no conclusions can be drawn from this analysis.
While the addition of JEMPERLI to carboplatin and paclitaxel resulted in improved PFS vs carboplatin and paclitaxel alone, we also have to be mindful of the side effects that may be associated with this regimen. So, in this setting, my chemotherapy nurses play a big role in helping to support the patients by assessing and identifying any and all side effects.
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JEMPERLI + CP Has an Established Safety Profile With Over 2 Years of Efficacy Follow-Up1,2
15% of patients receiving JEMPERLI + CP permanently discontinued JEMPERLI due to ARs1
- ARs leading to discontinuation were reported in 8 patients, including 1 case each of rash maculo-papular, fatigue, general physical health deterioration, acute kidney injury, infusion-related reaction, keratitis, muscular weakness, and myelosuppression1
- The most common ARs, including laboratory abnormalities (≥20%), were decreased hemoglobin, decreased white blood cell count, decreased platelets, decreased lymphocytes, increased glucose, increased alkaline phosphatase, decreased neutrophils, rash, diarrhea, increased aspartate aminotransferase, increased alanine aminotransferase, decreased sodium, hypothyroidism, and hypertension1
- Serious ARs occurred in 13% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel; the most common serious AR was sepsis, including urosepsis (6%)1
- Fatal ARs occurred in 6% of patients receiving JEMPERLI including septic shock (3.8%) and myelosuppression (1.9%)1
[Table] Adverse Reactions (≥10%) in Patients With dMMR/MSI-H Endometrial Cancer Who Received JEMPERLI + CP in RUBY1
Adverse Reaction; JEMPERLI (n=52) with Carboplatin and Paclitaxel; All Grades, %; Grade 3 or 4, %; Placebo (n=65) with Carboplatin and Paclitaxel; All Grades, %; Grade 3 or 4, %
Skin & Subcutaneous Tissue
Rash*; 42; 8; 20; 0
Dry Skin; 12; 0; 8; 0
Gastrointestinal Disorders
Diarrhea; 40; 1.9; 31; 0
Endocrine Disorders
Hypothyroidism†; 23; 0; 6; 0
Vascular Disorders
Hypertension; 21; 10; 11; 6
General & Administration Site
Pyrexia; 14; 0; 1.5; 0
Graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
* Includes rash, rash maculo-papular, palmar-plantar erythrodysesthesia syndrome, rash pustular, skin exfoliation, vulvovaginal rash, and dermatitis bullous.1 † Includes hypothyroidism and immune-mediated hypothyroidism.1
AR, adverse reaction; CP, carboplatin-paclitaxel; dMMR, mismatch repair deficient; MSI-H, microsatellite instability-high.
1. JEMPERLI. Prescribing Information. GSK; 2024. 2. Mirza MR, et al. N Engl J Med. 2023;388(23):2145–2158.
CECELIA BOARDMAN:
In the dMMR or MSI-high subgroup, JEMPERLI plus chemotherapy has an established safety profile with over 2 years of efficacy follow-up. Fifteen percent of patients receiving JEMPERLI plus chemotherapy permanently discontinued JEMPERLI due to adverse reactions, which included one case each of maculo-papular rash, fatigue, general physical health deterioration, acute kidney injury, infusion-related reaction, keratitis, muscular weakness, and myelosuppression.
The most common adverse reactions, including laboratory abnormalities, in at least 20% of patients, were decreased hemoglobin, decreased white blood cell count, decreased platelets, decreased lymphocytes, increased glucose, increased alkaline phosphatase, decreased neutrophils, rash, diarrhea, increased AST, increased ALT, decreased sodium, hypothyroidism, and hypertension.
Serious adverse reactions occurred in 13% of patients receiving JEMPERLI plus chemotherapy. The most common serious adverse reaction was sepsis, including urosepsis occurring in 6% of patients. Fatal adverse reactions occurred in 6% of patients receiving JEMPERLI including 3.8% with septic shock and 1.9% with myelosuppression.
The table on the right shows the adverse reactions in at least 10% of patients with dMMR or MSI-high endometrial cancer who received JEMPERLI plus chemotherapy in the RUBY trial.
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Laboratory Abnormalities
[Table] Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥10% of Patients with dMMR/MSI-H Endometrial Cancer Receiving JEMPERLI + CP in RUBY
Laboratory Test; JEMPERLI (n=52) with Carboplatin and Paclitaxel; All Grades,* %; Grade 3 or 4,* %; Placebo (n=65) with Carboplatin and Paclitaxel; All Grades,* %; Grade 3 or 4,* %
Hematology
Decreased Hemoglobin; 77; 17; 86; 25
Decreased Platelets; 54; 10; 57; 12
Decreased Lymphocytes; 52; 13; 51; 25
Decreased Neutrophils; 46; 21; 58; 23
Decreased White Blood Cell Count; 73; 15; 68; 14
Chemistry
Increased Glucose; 50; 13; 54; 11
Increased Alkaline Phosphatase†; 48; 6; 26; 0
Increased Aspartate Aminotransferase†; 40; 8; 25; 0
Increased Alanine Aminotransferase†; 40; 4; 26; 0
Electrolytes
Decreased Sodium; 29; 12; 26; 5
* Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. † Increased alkaline phosphatase, increased aspartate aminotransferase and increased alanine aminotransferase worsened from baseline to Grade 3 or 4 in <10% of patients.
CP, carboplatin-paclitaxel; dMMR, mismatch repair deficient; MSI-H, microsatellite instability-high.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
Laboratory abnormalities can also occur with JEMPERLI plus chemotherapy. This table summarizes laboratory abnormalities that worsened from baseline to Grade 3 or 4 occurring in at least 10% of patients with dMMR or MSI-high endometrial cancer receiving JEMPERLI plus chemotherapy in the RUBY trial. In the first column, the laboratory abnormalities are divided into hematology, chemistry, and electrolytes categories, and the other 2 main columns are the treatment arms: JEMPERLI plus chemotherapy and placebo plus chemotherapy groups. A full description of laboratory abnormalities and adverse reactions can be found in the full prescribing information for JEMPERLI.
Additional Important Safety Information will now be shared.
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IMPORTANT SAFETY INFORMATION (cont’d):
Immune-Mediated Pneumonitis, Colitis, and Hepatitis
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 2.3% (14/605) of patients, including Grade 2 (1.3%), Grade 3 (0.8%), and Grade 4 (0.2%) pneumonitis.
Immune-Mediated Colitis
- Colitis occurred in 1.3% (8/605) of patients, including Grade 2 (0.7%) and Grade 3 (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 0.5% (3/605) of patients.
PD-1, programmed death receptor-1; PD-L1, programmed death ligand-1.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
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 2.3% or 14 out of 605 patients, including Grade 2 (1.3%), Grade 3 (0.8%), and Grade 4 (0.2%) pneumonitis.
Immune-mediated colitis occurred in 1.3% or 8 out of 605 patients, including Grade 2 (0.7%) and Grade 3 (0.7%) adverse reactions. Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies.
JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.5% or 3 out of 605 patients.
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IMPORTANT SAFETY INFORMATION (cont’d):
Immune-Mediated Endocrinopathies
[Table] Immune-Mediated Endocrinopathies
Adrenal Insufficiency; Adrenal insufficiency occurred in 1.2% (7/605) of patients, including Grade 2 (0.5%) and Grade 3 (0.7%). 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. Grade 3 hypophysitis occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypophysitis occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
Thyroid Disorders; Grade 2 thyroiditis occurred in 0.5% (3/605) of patients. Grade 2 hypothyroidism occurred in 12% (28/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypothyroidism occurred in 8% (46/605) of patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism occurred in 2.3% (14/605) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.2%). Initiate thyroid 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. Grade 3 type 1 diabetes mellitus occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. 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.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
Adrenal insufficiency occurred in 1.2% or 7 out of 605 patients, including Grade 2 (0.5%) and Grade 3 (0.7%). 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.
JEMPERLI can cause immune-mediated hypophysitis. Grade 3 hypophysitis occurred in 0.4% or 1 out of 241 patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypophysitis occurred in 0.2% or 1 patient out of 605 patients receiving JEMPERLI as a single agent. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
Grade 2 thyroiditis occurred in 0.5% or 3 out of 605 patients. Grade 2 hypothyroidism occurred in 12% or 28 out of 241 patients receiving JEMPERLI in combination with chemotherapy. Grade 2 hypothyroidism occurred in 8% or 46 out of 605 patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% or 8 out of 241 patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism occurred in 2.3% or 14 out of 605 patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.2%). Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Grade 3 type 1 diabetes mellitus occurred in 0.4% or 1 out of 241 patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.2% or 1 out of 605 patients receiving JEMPERLI as a single agent. 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.
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IMPORTANT SAFETY INFORMATION (cont’d):
Immune-Mediated Nephritis With Renal Dysfunction, and Dermatologic Adverse Reactions
Immune-Mediated Nephritis With Renal Dysfunction
- JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.5% (3/605) of patients.
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.
PD-1, programmed death receptor-1; PD-L1, programmed death ligand-1.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.5% or 3 out of 605 patients.
JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, 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.
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IMPORTANT SAFETY INFORMATION (cont’d):
Other Immune-Mediated Adverse Reactions
Other Immune-Mediated Adverse Reactions
[Table] The following clinically significant immune-mediated adverse reactions occurred in <1% of the 605 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-Barré 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, other transplant (including corneal graft) rejection
PD-1, programmed death receptor-1; PD-L1, programmed death ligand-1.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
The following clinically significant immune-mediated adverse reactions occurred in less than 1% of the 605 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 adverse reactions included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, and autoimmune neuropathy. Cardiac or vascular adverse reactions included myocarditis, pericarditis, vasculitis. Ocular adverse reactions included 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 adverse reactions included pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and connective tissue adverse reactions included myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica. An endocrine adverse reaction included hypoparathyroidism. Other (hematologic/immune) adverse reactions included autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
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IMPORTANT SAFETY INFORMATION (cont’d):
Infusion-Related Reactions, and Complications of Allogeneic HSCT
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% (1/605) 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.
PD-1, programmed death receptor-1; PD-L1, programmed death ligand-1.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
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% or 1 out of 605 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.
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation 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.
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IMPORTANT SAFETY INFORMATION (cont’d):
Embryo-Fetal Toxicity and Lactation, and Common Adverse Reactions
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/MSI-H EC who received JEMPERLI in combination with carboplatin and paclitaxel were rash, diarrhea, hypothyroidism, and hypertension. The most common Grade 3 or 4 laboratory abnormalities (≥10%) were decreased neutrophils, decreased hemoglobin, decreased white blood cell count, decreased lymphocytes, increased glucose, decreased sodium, and decreased platelets.
The most common adverse reactions (≥20%) in patients with dMMR EC who received JEMPERLI as a single agent were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased lymphocytes, decreased sodium, increased alanine aminotransferase, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase.
dMMR, mismatch repair deficient; EC, endometrial cancer; MSI-H, microsatellite instability-high.
JEMPERLI. Prescribing Information. GSK; 2024.
CECELIA BOARDMAN:
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.
The most common adverse reactions in at least 20% of patients with dMMR or MSI-high endometrial cancer who received JEMPERLI in combination with chemotherapy were rash, diarrhea, hypothyroidism, and hypertension. The most common Grade 3 or 4 laboratory abnormalities in at least 10% of patients were decreased neutrophils, decreased hemoglobin, decreased white blood cell count, decreased lymphocytes, increased glucose, decreased sodium, and decreased platelets.
The most common adverse reactions in at least 20% of patients with dMMR endometrial cancer who received JEMPERLI as a single agent were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. The most common Grade 3 or 4 laboratory abnormalities in more than 2% of patients were decreased lymphocytes, decreased sodium, increased ALT, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase.
For more information, please see the full Prescribing Information for JEMPERLI.
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THANK YOU!
Questions? Please contact Medical Information at GSK, or visit JEMPERLIHCP.com
Paid consultant to GSK at the time of filming.
CECELIA BOARDMAN:
Thank you for watching this informational video about JEMPERLI in combination with carboplatin and paclitaxel for the treatment of dMMR/MSI-high primary advanced or recurrent endometrial cancer.
If you have any questions or would like to know more, please contact Medical Information at GSK, or visit JEMPERLIHCP.com.
On behalf of GSK and myself, thank you for your time and attention.
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PMUS-DSTVID240001 May 2024
Produced in USA.
