- Jemperli approval now includes MMRp/MSS tumors, which represent majority of endometrial cancer cases
- Jemperli plus chemotherapy demonstrated a statistically significant and clinically meaningful 31% reduction in risk of death versus chemotherapy alone
PHILADELPHIA, PA, USA I August 01, 2024 I GSK plc (LSE/NYSE: GSK) today announced the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab-gxly) in combination with carboplatin and paclitaxel (chemotherapy) followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This approval broadens the previous indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options. The supplemental Biologics License Application (sBLA) supporting this expanded indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status. We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumors where treatment options have been limited.”
Today’s expanded approval is based on results from dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS) from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a statistically significant OS benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.
At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group compared to 49% (95% CI: 43-55) in the chemotherapy group were alive. In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, diarrhea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy and vomiting.
Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: “The initial approval of Jemperli plus chemotherapy was practice-changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and today’s expanded approval will offer even more patients the opportunity for improved outcomes. This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”
Adrienne Moore, Survivor, Founding Member and President of Endometrial Cancer Action Network for African-Americans (ECANA) said: “With this expanded approval for Jemperli plus chemotherapy, GSK is bringing a much-needed new treatment regimen to the endometrial cancer community that may help patients with primary advanced or recurrent endometrial cancer live longer, providing hope to patients and their families. Survivors and advocates should be excited by today’s news and especially delighted that this approval means that more patients in the US who are diagnosed with endometrial cancer will have a new treatment option.”
About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumors.6
About RUBY
RUBY is a two-part global, randomized, double-blind, multi-center phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.
In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumors v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.
In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.
RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organization dedicated to transforming the standard of care in gynecologic oncology.
About Jemperli (dostarlimab-gxly)
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development program. A robust clinical trial program includes studies of Jemperli alone and in combination with other therapies in gynecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.
Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialization, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist.
Indications and Important Safety Information for JEMPERLI (dostarlimab-gxly)
- 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, 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. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Please see the full US Prescribing Information for JEMPERLI, including Medication Guide.
GSK in oncology
Oncology is an emerging therapeutic area for GSK where we are committed to maximizing patient survival with a current focus on hematologic malignancies, gynecologic cancers and other solid tumors through breakthroughs in immuno-oncology and tumor-cell targeting therapies.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at us.gsk.com.
SOURCE: GlaxoSmithKline
Post Views: 5,132
- Jemperli approval now includes MMRp/MSS tumors, which represent majority of endometrial cancer cases
- Jemperli plus chemotherapy demonstrated a statistically significant and clinically meaningful 31% reduction in risk of death versus chemotherapy alone
PHILADELPHIA, PA, USA I August 01, 2024 I GSK plc (LSE/NYSE: GSK) today announced the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab-gxly) in combination with carboplatin and paclitaxel (chemotherapy) followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This approval broadens the previous indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options. The supplemental Biologics License Application (sBLA) supporting this expanded indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status. We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumors where treatment options have been limited.”
Today’s expanded approval is based on results from dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS) from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a statistically significant OS benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.
At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group compared to 49% (95% CI: 43-55) in the chemotherapy group were alive. In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, diarrhea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy and vomiting.
Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: “The initial approval of Jemperli plus chemotherapy was practice-changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and today’s expanded approval will offer even more patients the opportunity for improved outcomes. This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”
Adrienne Moore, Survivor, Founding Member and President of Endometrial Cancer Action Network for African-Americans (ECANA) said: “With this expanded approval for Jemperli plus chemotherapy, GSK is bringing a much-needed new treatment regimen to the endometrial cancer community that may help patients with primary advanced or recurrent endometrial cancer live longer, providing hope to patients and their families. Survivors and advocates should be excited by today’s news and especially delighted that this approval means that more patients in the US who are diagnosed with endometrial cancer will have a new treatment option.”
About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumors.6
About RUBY
RUBY is a two-part global, randomized, double-blind, multi-center phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.
In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumors v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.
In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.
RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organization dedicated to transforming the standard of care in gynecologic oncology.
About Jemperli (dostarlimab-gxly)
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development program. A robust clinical trial program includes studies of Jemperli alone and in combination with other therapies in gynecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.
Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialization, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist.
Indications and Important Safety Information for JEMPERLI (dostarlimab-gxly)
- 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, 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. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Please see the full US Prescribing Information for JEMPERLI, including Medication Guide.
GSK in oncology
Oncology is an emerging therapeutic area for GSK where we are committed to maximizing patient survival with a current focus on hematologic malignancies, gynecologic cancers and other solid tumors through breakthroughs in immuno-oncology and tumor-cell targeting therapies.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at us.gsk.com.
SOURCE: GlaxoSmithKline
Post Views: 5,132
