A Treatment Option for Patients With Primary Advanced or Recurrent Endometrial Cancer

01/06/2025


Learn how JEMPERLI in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, may be an appropriate option to treat patients with primary advanced or recurrent endometrial cancer.

Dr Bradley Monk: Greetings and welcome. My name is Brad Monk, I’m a gynecologic oncologist from West Palm Beach, Florida, part of Florida Cancer Specialist and Research Institute. It's also my privilege and pleasure to be part of the GOG Partners Organization.

Dr Dana Chase: And I'm Doctor Dana Chase. I'm also a gynecologic oncologist at UCLA. On behalf of GSK and ourselves, thank you for your time and attention. We are presenting this program on behalf of GSK, the sponsor, and we are being compensated by GSK for our time for this service. 

Today we will discuss how JEMPERLI or dostarlimab in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, may be an appropriate option to treat patients with primary advanced or recurrent endometrial cancer. 

Before we begin, let’s review GSK’s Commitment to Transparency and Education: GSK believes transparent scientific dialogue is in the interest of all those working to develop new medicines; it improves clinical practice and advances care for patients. GSK’s goal in peer discussion, led by clinical experts, like ourselves, is to inform prescribers and caregivers about clinical data and relevant clinical experience relating to our innovative medicines. This program contains evidence-based, truthful, and balanced information, and we may share clinical experience consistent with the FDA-approved label. GSK is committed to transparency of financial relationships with healthcare professionals.

Dr Bradley Monk: In this video, we will briefly review the incidence of endometrial cancer and the importance of mismatch repair or microsatellite instability, MMR or MSI, biomarker testing. We will then learn about the efficacy and safety data of JEMPERLI in combination with carboplatin and paclitaxel, which we will refer to as JEMPERLI plus chemo occasionally, followed by JEMPERLI as a single agent for primary advanced or recurrent endometrial cancer as investigated in the RUBY Part 1 clinical trial. Additionally, throughout the video, we will look at the Important Safety Information for JEMPERLI.

Let’s start by reviewing the indication for JEMPERLI based on the RUBY Part 1 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.

Important Safety Information for JEMPERLI includes severe and fatal immune-mediated adverse reactions. 

Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ 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, thyroid function 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 Grade 1 or lower. Upon improvement to Grade 1 or lower, 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.

Now, Dr Chase will discuss some background information on endometrial cancer.

Dr Dana Chase: Thank you for that introduction, Dr Monk. As mentioned, let’s now begin reviewing some information on endometrial cancer.

More than 61,000 new diagnoses of endometrial cancer are projected for 2024. Endometrial cancer has the second highest rate of death among gynecologic cancers in the United States, with approximately 12,000 deaths expected this year. The bar graph on the right shows data for uterine cancer based on disease stage. The blue bar indicates 5-year relative survival, and the grey bar correlates to the percent of cases at diagnosis. Most patients are diagnosed with localized disease and have a 5-year relative survival of 95%. However, those with more advanced endometrial cancer have an especially poor prognosis, with an estimated 5-year relative survival rate of 19% for patients with distant disease at diagnosis. Although aggressive, non-endometrioid histologies account for only up to 20% of endometrial cancers, they actually account for more than 40% of endometrial cancer deaths.

Testing may provide important information about your patients.

Approximately 25% to 30% of endometrial tumors are mismatch repair deficient and microsatellite instability-high, also known as dMMR and MSI-high, while the rest are mismatch repair proficient and are microsatellite stable, also known as MMRp and MSS. The dMMR endometrial cancer tumors can be associated with a higher recurrence rate, higher rate of distant recurrences, and a mutation that increases the risk of Lynch syndrome, which is an inherited condition that increases the risk of endometrial cancer. 

There are 3 modalities to test dMMR and MSI-high status — immunohistochemistry, or IHC, PCR and NGS. Immunohistochemistry visually analyzes protein expression in the tumor and detects dMMR tumors, which are missing the expression of at least 1 MMR protein. PCR and NGS molecularly analyze changes in microsatellite loci length or regions, due to insertions or deletions of DNA repeats compared to normal tissue; MSI-high tumors are those with unstable DNA repeats. Due to the risks associated with dMMR and MSI-high endometrial cancer, MMR or MSI testing is recommended for all endometrial cancer patients with primary advanced or recurrent endometrial cancer.

Now, it’s important to note that patients with primary advanced or recurrent endometrial cancer need additional treatment options.

An additional treatment option is immune checkpoint inhibitors in combination with chemotherapy, which may improve treatment response in certain patients. Due to increased mutations that promote antitumor immune cell reaction and increased tumor-infiltrating lymphocytes, dMMR and MSI-high tumors are more likely to respond to anti–PD-1 therapies. Cytotoxic chemotherapy promotes antitumor immunity by inducing immunogenic cell death, which increases intratumoral T-cell infiltration.

Now, let's review more Important Safety Information about JEMPERLI.

JEMPERLI can cause immune-mediated pneumonitis, colitis, and hepatitis. 

Immune-mediated pneumonitis can be fatal. And in patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who’ve actually received prior thoracic radiation. Pneumonitis occurred in 2.3% of patients, including Grade 2, at 1.3%, Grade 3, 0.8%, and Grade 4, 0.2%, pneumonitis. 

Colitis occurred in 1.3% of patients, including Grade 2, at 0.7%, and Grade 3, at 0.7%, adverse reactions. Cytomegalovirus infection or reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating an infectious workup to exclude alternative etiologies. 

Immune-mediated hepatitis can also be fatal, and Grade 3 hepatitis occurred in 0.5% of patients.

JEMPERLI can also cause immune-mediated endocrinopathies, such as adrenal insufficiency, hypophysitis, thyroid disorders, and type 1 diabetes mellitus, which can present with diabetic ketoacidosis.

Adrenal insufficiency occurred in 1.2% of patients, including Grade 2, at 0.5%, and Grade 3, at 0.7%. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per your institutional guidelines, including hormone replacement as clinically indicated. Now, withhold or permanently discontinue JEMPERLI, or dostarlimab, depending on severity. 

JEMPERLI can cause immune-mediated hypophysitis, as well. Grade 3 hypophysitis occurred in 0.4% of patients receiving JEMPERLI in combination with carboplatin paclitaxel. Grade 2 hypophysitis occurred in 0.2% of 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% of patients. Grade 2 hypothyroidism occurred in 12% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypothyroidism occurred in 8% of patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2, at 2.9%, and Grade 3, at 0.4%. Hyperthyroidism occurred in 2.3% of patients receiving JEMPERLI as a single agent, including Grade 2, at 2.1%, and Grade 3, at 0.2%. Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. And withhold or permanently discontinue JEMPERLI depending on severity.

Now lastly, JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Grade 3 type 1 diabetes mellitus occurred in 0.4% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.2% of patients receiving JEMPERLI as a single agent. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. And initiate treatment with insulin as clinically indicated. And then, withhold or permanently discontinue JEMPERLI depending on severity.

Additional Important Safety Information will be reviewed later in this video.

Now, Dr Monk will begin discussing the trial results from RUBY Part 1.

Dr Bradley Monk: Thank you, Dr Chase. 

Now that we have reviewed some background information on endometrial cancer, we will now discuss the results of RUBY Part 1, this clinical trial that investigated JEMPERLI in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent in primary advanced or recurrent endometrial cancer.

RUBY Part 1 was a randomized, multicenter, double-blind, placebo-controlled trial conducted in 494 patients with primary advanced or recurrent endometrial cancer. The randomization for this patient population was stratified by MMR/MSI status, prior external pelvic radiation, and disease status. Patients were randomized 1:1 to either of the 2 treatment arms. The experimental arm received JEMPERLI plus chemotherapy every 3 weeks for 6 cycles. And then after the 3 weeks, starting with cycle 7, patients received 1000 mg of JEMPERLI monotherapy every 6 weeks. The control group received placebo plus chemotherapy every 3 weeks for 6 cycles; and then after 3 weeks, starting with cycle 7, received placebo every 6 weeks. Treatment continued until disease progression, unacceptable toxicity, or a maximum of 3 years.

Major endpoints included overall survival in all-comers, also described as the overall population, and progression-free survival in all-comers and the dMMR/MSI-high population. Prespecified exploratory analyses included OS in the dMMR/MSI-high population and both PFS and OS in the MMRp/MSS population.

Additional efficacy endpoints included objective response rate and duration of response in all-comers and the dMMR/MSI-high population.

This slide highlights the key eligibility criteria for the RUBY Part 1 trial. It included patients with broad disease characteristics, including those with primary FIGO stage III or stage IV disease including patients with more aggressive histologies, such as carcinosarcoma, 9%, and serous adenocarcinoma, 21%. The trial also accepted patients with first recurrent endometrial cancer with a low potential for cure by radiation therapy or surgery alone or in combination, including those naïve to systemic anticancer therapy, or those who had received prior neoadjuvant or adjuvant systemic anticancer therapy and who had a recurrence or disease progression for at least 6 months after completing treatment, first recurrence. 

Additionally, patients also had to be anti–PD-1, or PD-L1, or PD-L2 naïve.

Here, we show the baseline characteristics for the all-comers patient population, comprising 494 patients. The median age was 65 years, and 51% of patients being 65 years or older. 77% of the patients were White, 12% Black, 3% Asian, and 3% Hispanic or Latino. 18% had primary stage III endometrial cancer, 34% had primary stage IV disease, and 48% had recurrent disease.

Overall, 24% of patients were dMMR/MSI-high and 76% were MMRp or MSS. While 54.7% of patients had endometrioid carcinoma, 8.9% had carcinosarcoma, 20.6% had serous adenocarcinoma, and 15.8% included all other histologies. 

Now, let’s review the efficacy data for the all-comers population, starting with one of the major efficacy endpoints, overall survival or OS.

The OS data showed a hazard ratio of 0.69, which means it demonstrated a statistically significant 31% reduction in the risk of death with JEMPERLI plus chemotherapy versus chemotherapy alone. The median OS was 44.6 months for the JEMPERLI plus chemotherapy group versus 28.2 months for the chemotherapy alone group.  The estimated Kaplan-Meier probability of overall survival at 24 months was 70.1% with JEMPERLI plus chemotherapy versus 54.3% with chemotherapy alone.

Another major efficacy endpoint in the all-comers population was progression-free survival, or PFS. PFS data showed a hazard ratio of 0.64, which means compared to chemotherapy alone, treatment with JEMPERLI resulted in a statistically significant 36% risk reduction of progression or death. The median PFS was 11.8 months for the JEMPERLI plus chemo group compared to 7.9 months for the chemo alone group.

Additionally, let’s review the overall response data, or ORR and the duration of response data, or DOR for the all-comers population treated with JEMPERLI plus chemotherapy versus chemo alone.

JEMPERLI plus chemo demonstrated an objective response rate of 68% after 25.4 months of median follow-up; 20% of these patients had a complete response and 48% had a partial response. In comparison, patients in the chemo alone group achieved an objective response rate of 57%, including 12% with a complete response and 45% with a partial response. The duration of response was also evaluated for patients with a confirmed partial or complete response, with the median duration of response being 10.8 months with JEMPERLI plus chemo compared with 6.4 months with chemo alone at 25.4 months median follow-up.

Now that we have reviewed the efficacy data for the all-comers population, let’s discuss the efficacy data for the dMMR/MSI-high subgroup, starting with a major efficacy endpoint, PFS.

PFS data showed a hazard ratio of 0.29, which means a groundbreaking 71% reduction in the risk of progression or death observed with JEMPERLI plus chemotherapy versus chemotherapy alone for the dMMR/MSI-high subgroup. The median PFS was 30.3 months for the JEMPERLI plus chemo group versus 7.7 months for the chemo alone group.

Next, overall survival, or OS, was a prespecified exploratory analysis for the dMMR/MSI-high subgroup and was not powered to detect treatment differences; results are descriptive. The median OS was not reached for the JEMPERLI plus chemotherapy group and was 30.8 months for the chemo alone group. The estimated Kaplan-Meier probability of overall survival at 24 months was 81.4% with JEMPERLI plus chemo and 53.6% with chemo alone.

Finally, let’s review the additional efficacy endpoints for the dMMR/MSI-high subgroup, objective response, and duration of response.

JEMPERLI plus chemo demonstrated an objective response rate of 74%; 26% of these patients had a complete response and 48% had a partial response. In comparison, patients in the chemo alone group achieved an objective response rate of 62%, including 11% with a complete response and 51% with a partial response. Median duration of response was not reached with JEMPERLI plus chemo and 5.4 months with chemo alone after 24.9 months median follow-up.

Let's now move on to discuss the MMRp/MSS subgroup, which had prespecified exploratory analyses of OS and PFS. These analyses were not powered to detect treatment differences, and the results are descriptive. 76% of patients in the overall population had MMRp/MSS biomarker status. In the OS analysis, the median OS was 32.5 months for the JEMPERLI plus chemo group compared to 28.2 months for the chemo alone group. In the PFS analysis, the median PFS was 9.8 months for the JEMPERLI plus chemo group compared to 7.9 months for the chemo alone group.

Dr Dana Chase: So now, I’m going to review some of the established safety profiles of JEMPERLI plus chemotherapy, with over 3 years of median efficacy follow-up.

This table summarizes the adverse reactions that occurred in at least 20% of patients who received JEMPERLI plus chemo in the RUBY Part 1 clinical trial. In the first column, the adverse reactions are divided into nervous system disorders; general; gastrointestinal disorders; skin and subcutaneous tissue; musculoskeletal and connective tissue; respiratory, thoracic and mediastinal disorders; metabolism and nutrition disorders; and infections and infestations. The other 4 subcolumns correlate to the percentage of patients in each treatment group who had an adverse reaction of any grade or of Grade 3 or 4. 

19% or 46 patients receiving JEMPERLI plus chemotherapy permanently discontinued JEMPERLI treatment due to adverse reactions. Adverse reactions that required permanent discontinuation in at least 2 patients included 3 cases of rash maculo-papular and 2 cases each of increased ALT, increased AST, diarrhea, pancreatitis, fatigue, pneumonitis, and arthralgia. 

The most common adverse reactions, including laboratory abnormalities occurring in at least 20% of patients, were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting.

Serious adverse reactions occurred in 39% of patients receiving JEMPERLI plus chemotherapy; the most common serious adverse reactions were sepsis, including urosepsis, and pulmonary embolism.

Fatal adverse reactions occurred in 1.2% of patients receiving JEMPERLI, including septic shock and myelosuppression.

Here, you will see a table that summarizes select laboratory abnormalities that worsened from baseline occurring in at least 20% of patients receiving JEMPERLI plus chemo in the RUBY Part 1 trial. In the first column, the laboratory abnormalities are divided into hematology, chemistry, and electrolytes, and the other 4 subcolumns correlate to the percentage of patients in each treatment group who had laboratory abnormalities of any grade or of Grade 3 or 4.

Now, let’s review more Important Safety Information.

JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.5% of patients. 

JEMPERLI can also cause immune-mediated rash or dermatitis. Bullous or 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 or exfoliative rashes.

But withhold or permanently discontinue JEMPERLI depending on severity.

Clinically significant immune-mediated adverse reactions that 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, are listed on this slide. Severe or fatal cases have been reported for some of these adverse reactions. This table shows the other immune-mediated adverse reactions, which are categorized into the classes in the left column, and the specific types of reactions shown in the right column. 

Immune-mediated adverse reactions affecting the nervous system included meningitis, encephalitis, myelitis, demyelination, myasthenia syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, and autoimmune neuropathy. 

Cardiac or vascular immune-mediated adverse reactions included myocarditis, pericarditis, and vasculitis.

Ocular immune-mediated adverse reactions included uveitis, iritis, and 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, and duodenitis. 

Musculoskeletal and connective tissue adverse reactions included myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, and polymyalgia rheumatica.

The endocrine immune-mediated adverse reaction was hypoparathyroidism.

Lastly, other hematologic or immune adverse reactions included autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis or Kikuchi lymphadenitis, sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, and other transplant, including corneal graft rejection.

As shown in the RUBY Part 1 clinical trial, combination therapy was given up front, followed by treatment with JEMPERLI monotherapy.

The dosing regimen for JEMPERLI is as follows: the first phase, Cycle 1 through Cycle 6, is combination therapy with JEMPERLI 500 mg plus carboplatin and paclitaxel every 3 weeks, and JEMPERLI must be administered prior to carboplatin and paclitaxel when given on the same day. Now, starting with Cycle 7, administer JEMPERLI 1000 mg, as monotherapy, every 6 weeks until disease progression, or unacceptable toxicity, or up to 3 years. 

JEMPERLI provides sustained target engagement as measured by direct PD-1 binding and stimulation of IL-2 production throughout the dosing interval at the recommended dosage. The JEMPERLI combination regimen of every 3 weeks allows for more frequent patient monitoring during the 6-cycle treatment initiation phase. However, the number of infusion visits is reduced after transitioning to every 6 weeks for the monotherapy phase.

Additional monitoring may be required per clinical discretion.

JEMPERLI is a monoclonal antibody that belongs to a class of drugs that bind to either PD-1 or PD-L1, blocking the PD-1 or PD-L1 pathway, this removes inhibition of the immune response, potentially breaking peripheral tolerance, and inducing 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 after starting a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, they can also manifest after discontinuation of treatment.

Important immune-mediated adverse reactions described in this video may not include all possible severe and fatal immune-mediated reactions.

This slide and the next slide describe the recommended dose modifications for adverse reactions for patients treated with JEMPERLI. Dose reduction is not recommended. And in general, withhold JEMPERLI for severe, Grade 3, immune-mediated adverse reactions and permanently discontinue JEMPERLI for life-threatening, Grade 4, immune-mediated adverse reactions, recurrent severe, Grade 3, immune-mediated adverse reactions that require systemic immunosuppressive treatment, or an inability to reduce the corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Dose modifications for JEMPERLI for adverse reactions that may require different management styles from these general guidelines are summarized in the next slide.

This table shows immune-mediated and other adverse reactions in the first column. Depending on the severity, which is shown in the middle column, recommended dose modifications, which can be found in the right column, include withholding, permanently discontinuing treatment, or interrupting or slowing the rate of infusion.

Please see JEMPERLI’s Prescribing Information to review the details of this table.

Lastly, let’s finish reviewing the rest of the Important Safety Information for JEMPERLI.

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% 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.

Fatal or 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.

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, including laboratory abnormalities, in patients with endometrial cancer who received JEMPERLI in combination with carboplatin and paclitaxel were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting.

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 alanine aminotransferase, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase.

Dr Bradley Monk: We will now summarize what we discussed.

JEMPERLI plus chemo is the first and only immuno-oncology combination with a statistically significant overall survival benefit versus chemo alone in all-comers. In the RUBY Part 1 clinical trial, a 16-month improvement in median overall survival for all-comers was reported with JEMPERLI plus chemo versus chemo alone. The median overall survival with JEMPERLI plus chemotherapy was 44.6 months versus 28.2 months with chemo alone; and there was a significant overall survival benefit with a hazard ratio of 0.69. The RUBY Part 1 study was based on a robust clinical trial design that included patients with aggressive histologies. Finally, JEMPERLI plus chemo has a well-established safety profile. The most common adverse reactions occurring in at least 20% of patients with JEMPERLI plus chemotherapy were peripheral neuropathy, fatigue, nausea, alopecia, arthralgia, rash, constipation, diarrhea, abdominal pain, dyspnea, decreased appetite, urinary tract infection, and vomiting.

Together with GSK Oncology provides resources for patients and healthcare professionals.

This program offers a variety of access and reimbursement services in an easy-to-access location for all GSK oncology products. Together with GSK Oncology offers the following: coverage support, co-pay assistance program for commercial patients, claims assistance, a patient assistance program for uninsured and Medicare patients, and referral to third-party support services. Together with GSK Oncology does not guarantee coverage or payer reimbursement.

For more information on Together with GSK Oncology, including eligibility, please refer to the phone number and website on this slide.

Thank you for watching this informational video about JEMPERLI in combination with carboplatin and paclitaxel for the treatment of primary advanced or recurrent endometrial cancer.

Dr Dana Chase: If you have questions or would like more information, please go to JEMPERLIHCP.com or contact GSK Oncology Medical Information. On behalf of GSK, myself, and Dr Monk, we thank you for your time and attention.

Indications

  • 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). 
  • JEMPERLI, as a single agent, is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced EC, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.

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 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.

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% (30/241) 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.

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. 

Other Immune-Mediated Adverse Reactions 

  • 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

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. 

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%), including laboratory abnormalities, in patients with EC who received JEMPERLI in combination with carboplatin and paclitaxel were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting. 

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.

Please see full Prescribing Information, including Medication Guide.

PM-US-DST-SMP-250003 March 2025