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JEMPERLI is indicated in combination with platinum-containing chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy.1
JEMPERLI is indicated as monotherapy for the treatment of adult patients with dMMR/ MSI-H recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen.1
The RUBY trial: Part 1 is a Phase 3, randomized, double-blind, multi-centre study of JEMPERLI plus carboplatin-paclitaxel versus placebo plus carboplatin/paclitaxel in patients with primary advanced or recurrent endometrial cancer2
Treatment:
Patients received either JEMPERLI 500mg or placebo intravenously in combination with carboplatin (AUC 5 mg/ml/min) and paclitaxel (175mg/m2) intravenously every 3 weeks for the first 6 cycles, followed by JEMPERLI 1000 mg or placebo intravenously every 6 weeks for up to 3 years.2
*Mixed histology containing at least 10% carcinosarcoma, clear cell or serous histology, †Primary stage III, primary stage IV or recurrent
¶Treatment ends after 3 years, PD, toxicity, withdrawal of consent, investigator's decision, or death, whichever occurs first. Continued treatment with JEMPERLI or placebo beyond 3 years may be considered following discussion between the Sponsor and the Investigator1,2
A robust trial design inclusive of patients with broad disease characteristics (n=118)1,2
- RUBY enrolled women aged ≥18 years with primary advanced or recurrent FIGO stage III or IV endometrial cancer.
- RUBY included patients with aggressive histologies, including carcinosarcoma, clear cell, serous and mixed (containing ≥10% carcinosarcoma, clear cell or serous)
- 23.9% of patients had dMMR tumours which reflects estimates in real-world endometrial cancer populations1,2
Primary Endpoint: Progression Free Survival in dMMR/MSI-H population2
▼ JEMPERLI (dostarlimab) + CP demonstrates statistically significant (P<0.0001) and clinically meaningful PFS benefit in patients with dMMR/MSI-H tumours
JEMPERLI + CP (N=53)
Placebo + CP (N=65)
Figure adapted from: Mirza et al. New England Journal of Medicine 2023
At 2 years, 61.4% of patients with dMMR/MSI-H tumours were alive and progression free in the JEMPERLI + CP arm vs 15.7% in the placebo + CP arm*
PFS by BICR was consistent with PFS by investigator assessment.
*The median duration of follow up was 24.8 months (range, 19.2-36.9)
Prespecified subgroup analysis: (not statistically powered) Overall Survival in dMMR/MSI-H population1
A pre-specified subgroup analysis found an 83.3% estimated probability of survival for patients with dMMR/MSI-H tumours who received JEMPERLI + CP at 2 years vs 58.7% with placebo + CP (HR, 0.30; 95% CI, 0.13-0.70)*†1,3
JEMPERLI + CP (N=53)
Placebo + CP (N=65)
Secondary Endpoint: ORR in dMMR/MSI-H population1,5
77.6% ORR in the JEMPERLI + CP arm vs 69.0% in the placebo + CP arm for patients with dMMR/MSI-H tumours*†5
ORR by BICR was consistent with ORR by investigator assessment**
*The median duration of follow-up was 24.8 months (range, 19.2-36.9)
†Number of patients with an ORR: n=38/49 in the JEMPERLI + CP group and n=40/58 in the placebo + CP group
**Assessed in patients with evaluable disease at baseline
Secondary Endpoint: Duration of Response in dMMR/MSI-H population5
At 2 years, 62.1% of women with dMMR/MSI-H tumours were still responding to JEMPERLI + CP vs 13.2% with placebo + CP*†5
In the dMMR/MSI-H population, median DOR was not reached (95% CI, 10.1-NE) with JEMPERLI + CP vs 5.4 months (95% CI, 3.9-8.1) with placebo + CP*†
DOR by BICR was consistent with DOR by investigator assessment
*The median duration of follow-up was 24.8 months (range, 19.2-36.9)
†Data had reached 60.3% maturity at interim analysis
In the dMMR population, JEMPERLI + CP maintained HRQoL vs placebo + CP1,5
Adapted from: Mirza et al. New England Journal of Medicine 2023
HRQoL = Health-related quality of life PRO assessments were completed before treatment on day 1 of each treatment cycle, the end of treatment visit, and at safety and survival follow-up visits.
EORTC QLQ-C30: Functional scales: Physical, role, emotional, cognitive, social; Symptoms: Fatigue, nausea & vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties
Overall Safety Profile from the RUBY Trial in the ITT (Intention to Treat) population
▼ JEMPERLI (dostarlimab) + CP offers a manageable safety profile consistent with the known profiles of its individual components after 2 years of follow-up1,2
The safety profile of dostarlimab-carboplatin-paclitaxel for patients with dMMR/MSI-H EC in the RUBY study (N=52) was similar to that of the overall combination therapy population1,4
| Parameter, n (%) |
JEMPERLI + carboplatin/paclitaxel (N=241) |
Placebo + carboplatin/paclitaxel (N=246) |
|---|---|---|
| Any TEAE | 241 (100) |
246 (100) |
| Any grade ≥3 TEAE | 170 (70.5) | 147 (59.8) |
| Serious TEAE | 91 (37.8) | 68 (27.6) |
| Any treatment-related irAE | 92 (38.2) | 38 (15.4) |
| Any TEAE leading to discontinuation of JEMPERLI or placebo | 42 (17.4) | 23 (9.3) |
| Any TEAE leading to discontinuation of carboplatin | 24 (10.0) | 19 (7.7) |
| Any TEAE leading to discontinuation of paclitaxel | 24 (10.0) | 23 (9.3) |
| Any TEAE leading to death | 5 (2.1)a | 0 |
| Any TEAE related to JEMPERLI leading to death | 2 (0.8)b | - |
| Median duration of overall treatment, (range) weeks | 43.0 (3.0–150.9) | 36.0 (2.1–165.1) |
The most common immune-related adverse events were hypothyroidism (11.2% of the patients in the dostarlimab group and 2.8% of those in the placebo group), rash (6.6% and 2.0%), arthralgia (5.8% and 6.5%), and an increase in alanine aminotransferase levels (5.8% and 0.8%).
a3 deaths were not related to study treatment (opiate overdose, COVID-19, and general physical health deterioriation). bOne death was considered by the investigator as related to JEMPERLI plus CP and occurred during the first 6 cycles (myelosuppression); one death was related to JEMPERLI and occurred during the 90-day safety follow-up (hypovolemic shock).
Events of any grade occurring in >20% of patients in either group2,4
| Dostarlimab (N=241) |
Placebo (N=246) |
|
|---|---|---|
| No. of patients (%) | ||
| Fatigue | 125 (51.9) | 134 (54.5) |
| Alopecia | 129 (53.5) | 123 (50.0) |
| Nausea | 130 (53.9) | 113 (45.9) |
| Peripheral neuropathy | 106 (44.0) | 101 (41.1) |
| Anaemia | 91 (37.8) | 104 (42.3) |
| Arthralgia | 86 (35.7) | 86 (35.0) |
| Constipation | 83 (34.4) | 88 (35.8) |
| Diarrhoea | 75 (31.1) | 71 (28.9) |
| Myalgia | 63 (26.1) | 68 (27.6) |
| Hypomagnesemia | 52 (21.6) | 70 (28.5) |
| Peripheral sensory neuropathy | 51 (21.2) | 47 (19.1) |
| Decreased appetite | 52 (21.6) | 43 (17.5) |
| Dyspnoea | 44 (18.3) | 50 (20.3) |
| Rash | 55 (22.8) | 34 (13.8) |
Table adapted from: Mirza et al. New England Journal of Medicine 2023
For full Safety information please refer to the Jemperli Summary of Product Characteristics
Grade ≥ 3 events occurring in >5% of patients in either group2
| Dostarlimab (N=241) | Placebo (N=246) | |
|---|---|---|
| No. of patients (%) | ||
| Anaemia | 36 (14.9) | 40 (16.3) |
| Neutropenia | 23 (9.5) | 23 (9.3) |
| Neutrophil count decreased | 20 (8.3) | 34 (13.8) |
| Lymphocyte count decreased | 13 (5.4) | 18 (7.3) |
| White-cell count decreased | 16 (6.6) | 13 (5.3) |
| Hypertension | 17 (7.1) | 8 (3.3) |
| Pulmonary embolism | 12 (5.0) | 12 (4.9) |
| Hypokalaemia | 12 (5.0) | 9 (3.7) |
Table adapted from: Mirza et al. New England Journal of Medicine 2023
For full Safety information please refer to the Jemperli Summary of Product Characteristics
Do you have questions about how JEMPERLI can support your patients?
Indications
JEMPERLI is indicated in combination with platinum-containing chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer (EC) who are candidates for systemic therapy.
JEMPERLI is indicated as monotherapy for the treatment of adult patients with dMMR/MSI-H recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen.
Footnotes
AUC, area under the curve; BICR; blinded independent central review; BSA, body surface area; BSLN, baseline; C, cycle; CI, confidence interval; CP, carboplatin/paclitaxel; dMMR, mismatch repair deficient; DOR, duration of response; EC, Endometrial Cancer; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EORTC, European Organization for Research and Treatment of Cancer; EN24, Quality of Life Questionnaire-Endometrial; EQ-5D-5L, EuroQoL 5-dimensions 5-levels; FIGO, International Federation of Gynecology and Obstetrics; IA, Interim analysis; INV, Investigator assessment; irAE, immune related adverse event; MSI-H, microsatellite instability-high; NE, not estimable; ORR, objective response rate; PD, Progression of disease; PFS, progression free survival; QOL, quality of life
References
- Jemperli (dostarlimab) Summary of Product Characteristics Great Britain
- Mirza MR, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158.
- Lorenzi M, et al. Epidemiology of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) in solid tumours: a structured literature review. J Oncol. 2020:1-17
- Mirza MR, et al. Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: a placebo-controlled randomized phase 3 trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). Presented at ESMO Virtual Plenary. 27-28 March 2023; Virtual.
- Mirza MR, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158 [Supplementary Appendix].
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Adverse events should also be reported to GSK Limited on 0800 221 441 or uksafety@gsk.com
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March 2024 ӏ PM-GB-DST-WCNT-230018 (V1.0)
