RUBY Part 2 trial results: Potentially practice changing results in advanced/recurrent endometrial cancer

The European Network for Gynaecological Oncological Trial (ENGOT) groups, the Nordic Society of Gynaecological Oncology – Clinical Trial Unit (NSGO-CTU) and the GOG Foundation, Inc. (GOG-F) are proud to collaborate with the study sponsor, GSK in the RUBY Part 2 trial.

The results reveal improvement in progression-free survival (PFS) at 12 months in the overall study population from 33.7% (carboplatin/paclitaxel [CP]+placebo+placebo) to 57.0% (CP+dostarlimab+niraparib), and in MMRp/MSS population from 31.1% (CP+placebo+placebo) to 54.7% (CP+dostarlimab+niraparib). “The trial’s results demonstrate statistically significant and clinically meaningful improvement in PFS of patients with primary advanced or recurrent endometrial cancer when treated with dostarlimab in combination with standard of care carboplatin/paclitaxel followed by dostarlimab and niraparib compared to chemotherapy alone, demonstrating a role for PARP inhibitor maintenance in patients receiving dostarlimab plus chemotherapy,” said Mansoor Raza Mirza (NSGO-CTU), global principal investigator of RUBY Part 2.

The trial results for RUBY Part 2 are presented on 16^th of March 2024 at the Society of Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer.

“Carboplatin/paclitaxel has been the standard of care for first-line treatment of primary advanced or recurrent endometrial cancer; however, long-term outcomes remained poor, with median overall survival of less than 3 years. Significant improvement in the PFS and Overall Survival in first-line systemic treatment by addition of dostarlimab was observed in RUBY Part 1,” said Mirza. “The results of RUBY Part 2 further improved the PFS outcome of our patients.”

Statement by ENGOT President Prof. Nicoletta Colombo:

“The results of the RUBY trial represent an incredible step forward in our battle against advanced endometrial cancer. If this regimen is approved, patients may benefit from a new first line standard of care that may significantly prolong PFS. Another success of the strong collaboration among gynaecologic oncology groups worldwide.”

Statement by GOG-F President Thomas Herzog, MD:

“The potentially practice changing results of this important trial will help many patients who are undergoing treatment for advanced endometrial cancer. ENGOT and the GOG-F goals are aligned, in improving the lives of patients through clinical trials. The important research collaborative allows discovery of novel effective therapies to transform the standard of care in gynecologic oncology.”

About RUBY Part 2 Trial
The RUBY Part 2 trial, sponsored by Tesaro Inc., a GSK group company, is a phase 3, randomized, double-blind, multicenter, placebo-controlled study. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomized 2:1 to receive dostarlimab, or placebo, plus CP combination, followed by dostarlimab + niraparib or placebo-placebo.  Of 291 patients randomized, 216 (74.2%) had MMRp/MSS tumors. PFS was significantly longer in the dostarlimab plus niraparib plus CP arm than the placebo-placebo plus CP arm in patients with MMRp/MSS tumors and in the overall population. In the MMRp/MSS population, the estimated Kaplan-Meier (KM) probability of PFS at 12 months was 54.7% (median 14.3 months 95% CI, 9.7–16.9) with dostarlimab-niraparib–CP and 31.1% (median 8.3 months 95% CI, 7.6–9.8) with placebo-placebo–CP (HR, 0.63; 95% CI, 0.44–0.91; P

 The study is sponsored by Tesaro Inc., a GSK Group company; RUBY ClinicalTrials.gov number, NCT03981796.)

About NSGO-CTU (www.nsgo.org)
The Nordic Society of Gynaecological Oncology – Clinical Trial Unit (NSGO-CTU) is a non-profit organization aiming to improve the practice of prevention, diagnosis and treatment for gynaecological cancers by supporting research and conducting clinical trials across countries.

About ENGOT (www.engot.esgo.org)
The European Network for Gynaecological Oncological Trial (ENGOT) groups is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Currently, ENGOT consists of 21 trial groups from 31 European countries that perform cooperative clinical trials. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial.

About The GOG Foundation, Inc. (www.gog.org)

The GOG Foundation, Inc. is a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis, and distribution of results.  The GOG Foundation is the only clinical trialist group in the United States that focuses its research on patients with pelvic malignancies, such as cancer of the ovary (including surface peritoneal malignancies), uterus (including endometrium, soft tissue sarcoma, and gestational trophoblastic neoplasia), cervix, and vulva. The GOG Foundation is multi-disciplinary in its approach to clinical trials, and includes gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, oncology nurses, biostatisticians (including those with expertise in bioinformatics), basic scientists, quality of life experts, data managers, and administrative personnel.

About the GOG Partners Program

Supported by industry, GOG Partners program is structured to work directly with pharmaceutical organizations and operate clinical trials outside the National Cancer Institute (NCI) framework. The GOG Partners program promotes the mission of the GOG Foundation dedicated to transforming the care in Gynecologic Oncology. By providing an alternative venue for patient accrual and site infrastructure support, GOG Partners has helped provide additional trials and opportunities for patients outside the national gynecologic clinical trials network.

About Endometrial Cancer

Endometrial cancer is the most common reproductive cancer affecting women within the United States, estimated to account for approximately 65,950 newly diagnosed cases in 2022. [ACS, 2022^a] Although the average age at diagnosis for women with endometrial cancer is 60 years, a proportion of patients are diagnosed prior to menopause. [ACS, 2022^a] Endometrial endometrioid adenocarcinoma is most commonly diagnosed when confined to the uterus, representing 67% of cases; however, the National Comprehensive Cancer Network (NCCN) reports that in 2017, 21% and 8% of cases were diagnosed as regional and distant diseases, respectively. [NCCN v1.2022^c]

Despite currently available treatment options, it was estimated that there would be nearly 12,550 endometrial cancer related deaths in the United States in 2022. [ACS, 2022^b] Unfortunately, women with metastatic and recurrent endometrial cancer have unfavourable prognosis, with an estimated 5-year survival rate of 20%. [ACS, 2022^b]

^aAmerican Cancer Society. Key Statistics for Endometrial Cancer. 2022, February 14.  Accessed on August 4, 2022 from https://www.cancer.org/cancer/endometrial-cancer/about/key-statistics.html

^bAmerican Cancer Society.  Survival Rates for Endometrial Cancer. 2022, February 28.  Accessed August 3, 2022 from https://www.cancer.org/cancer/endometrial-cancer/detection-diagnosis-staging/survival-rates.html

^cNational Comprehensive Cancer Network. Uterine Neoplasms. Version 1.2022-November 4, 2021. Accessed on August 10, 2022 from https://www.nccn.org/professionals/physician_gls/pdf/uterine.pd