On October 17, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported updated results from the KRYSTAL-7 Phase 2 study evaluating adagrasib combined with pembrolizumab in patients for the treatment of first-line NSCLC harboring a KRASG12C mutation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) 2023 (Press release, Mirati, OCT 17, 2023, View Source [SID1234636084]). These data demonstrate a manageable safety profile and early signs of durability of adagrasib in combination with a checkpoint inhibitor in the first-line NSCLC setting.

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Summary of Clinical Results

In patients with PD-L1 TPS ≥50%, adagrasib and pembrolizumab demonstrated an overall response rate (ORR) of 63% and disease control rate (DCR) of 84% and promising early signs of durability. The 63% confirmed response rate compares favorably to pembrolizumab monotherapy which has demonstrated an ORR of 39-45%.1,2
A median progression free survival has not been reached at 10.1 months median follow up.
The safety profile of the adagrasib and pembrolizumab combination was consistent with either agent as monotherapy, with a low rate of treatment related adverse events (TRAEs) leading to discontinuation of both drugs in only 4% of patients.
Treatment related hepatic events occurred in <10% of patients and were predominantly low grade. No patients discontinued both adagrasib and pembrolizumab due to ALT/AST increase or hepatic-related TRAEs.
"Data presented to date indicate that adagrasib prescribed following or in combination with immunotherapy offers a tolerable safety regimen for first-line NSCLC patients with a KRASG12C mutation," said Marina C. Garassino, M.D., professor of medicine, UChicago Medicine. "Adagrasib is the only KRASG12C inhibitor to be feasibly combined concurrently or following immunotherapy with a well-managed hepatoxicity profile, and still exhibits positive efficacy signals."

"We are pleased to see these significant findings, which further support the initiation of a global Phase 3 study evaluating the combination of adagrasib plus immunotherapy in the first-line setting for KRASG12C-mutated NSCLC with PD-L1 TPS ≥50% for the benefit of patients," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics. "Potential combinability with an immunotherapy, in addition to encouraging clinical activity in other tumor types and demonstrated central nervous system (CNS) penetration, reinforces our confidence in the differentiation of adagrasib from other potential treatment options and the benefit it offers to patients."

Mirati plans to initiate a Phase 3 clinical study to evaluate adagrasib in combination with pembrolizumab in the first line setting for KRASG12C-mutated NSCLC with PD-L1 TPS ≥50%. Initial patient enrollment is expected by year-end 2023.

On October 17, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that the registrational Phase III study (HQP1351AG301, NCT06051409) of olverembatinib, Ascentage Pharma’s lead drug candidate, combined with chemotherapy, versus imatinib combined with chemotherapy in treatment-naïve patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has dosed its first patient (Press release, Ascentage Pharma, OCT 17, 2023, View Source [SID1234636083]). As a global best-in-class drug, olverembatinib holds the promise of becoming the first tyrosine kinase inhibitor (TKI) approved in China for the first-line treatment of Ph+ ALL.

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This global multi-center, randomized-controlled, open-label, registrational Phase III study (HQP1351AG301) is designed to evaluate the efficacy and safety of olverembatinib combined with chemotherapy versus imatinib combined with chemotherapy in newly-diagnosed patients with Ph+ ALL.

Accounting for 20%-30% of all ALL cases in adults, Ph+ ALL is commonly associated with a high relapse rate, short progression-free survival, and poor prognosis. Prior to the introduction of TKIs, a class of targeted small molecule compounds, allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving complete responses (CRs) from chemotherapy was widely adopted as a first-line treatment for patients with Ph+ ALL. However, the five-year overall survival (OS) was only less than 30% and more than 70% patients relapsed before the transplantation or simply lacked access to the surgical treatment[1].

The clinical adoption of TKIs has resulted in a new clinical paradigm for patients with Ph+ ALL. However, first and second-generation TKIs have known clinical limitations, including high relapse rates and disappointing long-term survival with a three to five-year OS rate of just about 50%[2]. These limitations are primarily caused by low complete molecular responses (CMRs) and T315I kinase domain mutations, thus leaving substantial room for improvement in the treatment of Ph+ ALL. Currently, no TKI has been approved for the first-line treatment of Ph+ ALL in China and third-generation TKIs with more potent efficacy can potentially provide better prognosis to patients with Ph+ ALL by inducing a higher rate of CMRs and inhibiting the T315I mutation.

Ascentage Pharma’s novel drug candidate, olverembatinib, is an orally-administered third-generation TKI and the first and only China-approved third-generation BCR-ABL inhibitor. Currently, olverembatinib is being jointly commercialized by Ascentage Pharma and Innovent Biologics. In November 2021, Olverembatinib was approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. Previously, olverembatinib received a recommendation from the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment Hematologic Malignancies as a treatment option for patients with Ph+ ALL.

(Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland)

Prof. Weili Zhao, Vice President of Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital and Director of Shanghai Institute of Hematology, commented, "Ph+ ALL used to be the most high-risk and difficult-to-treat subtype of leukemia and the introduction of TKIs has resulted in improved prognosis to patients with this condition. However, clinicians face the pressing question of which TKI offers the best efficacy and safety. We hope HQP1351AG301, a clinical study evaluating olverembatinib, a China-developed next-generation TKI, can provide an answer to those important questions."

Prof. Suning Chen, Deputy Director of the Hematology Department, the First Affiliated Hospital of Soochow University and Deputy Director of Jiangsu Institute of Hematology, noted, "Since its launch, olverembatinib showed excellent efficacy in patients with Ph+ ALL. We are very hopeful for the results from the HQP1351AG301 trial, as it is the first registrational clinical study for the first-line treatment of patients with Ph+ ALL."

Prof. Yang Shen, Deputy Director of the Hematology Department at Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital, commented, "Olverembatinib has already been approved for the treatment of chronic myeloid leukemia in China. The HQP1351AG301 trial evaluates olverembatinib in Ph+ ALL, a potential additional indication in which olverembatinib has already showed promising therapeutic utility according to existing real-world data. We hope olverembatinib will offer a new treatment option to patients with Ph+ ALL."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "At present, the long-term survival rate of patients with Ph+ ALL remains disappointing, thus leaving considerable room for improvement. Multiple studies have shown that more potent third-generation TKIs can offer durable responses and a higher survival rate to patients with Ph+ ALL, yet no TKIs have been approved for the first-line setting in China. We are glad that this registrational Phase III study of olverembatinib, a TKI that could potentially become the first one approved in China for the first-line treatment of Ph+ ALL, has successfully enrolled and dosed its first patient. Moving forward, we will actively advance this clinical program and try to bring this drug to market as soon as possible for the benefit of more patients."

On October 17, 2023 STORM Therapeutics Ltd. (STORM), a clinical stage biotechnology company discovering and developing novel small molecule therapies targeting RNA modifying enzymes (RMEs) for oncology and other diseases, reported that Dr. Yaara Ofir-Rosenfeld, Director of Translational Oncology at STORM, presented novel pre-clinical data investigating the combination of METTL3 inhibitors (METTL3i) with DNA damaging therapies at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, Massachusetts on the 11-15 October 2023 (Press release, STORM Therapeutics, OCT 17, 2023, View Source [SID1234636082]).

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The presentation entitled "STC-15, a small molecule inhibitor of the RNA methyltransferase METTL3, activates anti-tumor immunity and reshapes the tumor microenvironment" detailed pre-clinical findings from STORM’s investigational drug STC-15 in combination with DNA damaging therapies. STC-15 is an orally bioavailable, highly selective METTL3 inhibitor and is the first molecule specifically targeting an RNA methyltransferase enzyme to enter clinical development.

STORM’s new data demonstrates that:

METTL3 inhibition enhances cytotoxicity of DNA damaging chemotherapies such as doxorubicin
Combination of STC-15 with chemotherapies activates cancer cell intrinsic interferon signalling that contributes to the induction of immunogenic cell death.
STC-15 synergises with radiation therapy in vivo
STC-15 reshapes the tumor microenvironment, shifting it from an immunosuppressive, pro-tumorigenic to an immune stimulatory, anti-tumor state
A first-in-human clinical trial on STORM’s lead clinical candidate STC-15 in patients with solid tumours is ongoing and can be found on clinicaltrials.gov under the identifier NCT05584111.

Yaara Ofir-Rosenfeld, Director of Translational Oncology of STORM Therapeutics, added, "Many tumours develop mechanisms that suppress their recognition by the immune system and limit their response to treatment. Our new findings reveal that STC-15 treatment shifts the tumour microenvironment to an immunostimulatory state and thereby boosts the efficacy of established cancer treatments such as radio- and chemotherapy."

Oliver Rausch, Chief Scientific Officer of STORM Therapeutics, commented, "These exciting new data build on our previous findings that STC-15 leads to activation of anti-tumor immunity and tumor killing. They illustrate a huge opportunity for STC-15 to be combined with a wide range of existing standard of care cancer drugs including checkpoint inhibitors and DNA damaging agents. This represents a major discovery for the STORM team as we look to develop STC-15 as a novel treatment option for cancer patients."

Details of the conference and presented abstract are as follow:

Abstract Title: STC-15, a small molecule inhibitor of the RNA methyltransferase METTL3, activates anti-tumor immunity and reshapes the tumor microenvironment

Presenter: Yaara Ofir-Rosenfeld1

Date and Time: Saturday, 14 October 2023, 12:30pm-4:00pm EDT

Location: Level 2, Exhibit Hall D

Poster number: C077

Session: Poster Session C

1STORM Therapeutics Ltd., Cambridge, UK

On October 17, 2023 Beyond Cancer, Ltd., an affiliate of Beyond Air, Inc. (NASDAQ: XAIR) that is developing ultra-high concentration nitric oxide (UNO) as an immunotherapeutic for solid tumors, reported the publication of pre-clinical data demonstrating that its proprietary technology reduces immunosuppression and creates a favorable microenvironment that can contribute to immune potentiation (Press release, Beyond Air, OCT 17, 2023, View Source [SID1234636081]).

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The data were published in an article entitled, "Intratumoral Administration of High-Concentration Nitric Oxide and Anti-mPD-1 Treatment Improves Tumor Regression Rates and Survival in CT26 Tumor-Bearing Mice," in the peer-reviewed journal Cells. The article is available on the Cells website. (click here).

"The combination of UNO and anti-mPD-1 resulted in a potent, synergistic immune response," stated Dr. Hila Confino, Head of In Vivo Studies. "This work aligns with prior data utilizing UNO to treat solid tumors and has repeatedly demonstrated increased tumor regression rates and improvement in survival."

Dr. Frederick Dirbas, MD, Associate Professor of Surgery, Div of Surgical Oncology, Dept of Surgery, Stanford University School of Medicine and Chair of the Beyond Cancer Scientific Advisory Board commented, "This manuscript details the beneficial effects of UNO alone and in conjunction with immunotherapy in a murine tumor model. The boost seen with the combination of UNO and immunotherapy is important. We look forward to further investigation exploring mechanisms of action of UNO as well as the potential merits of UNO in treating human solid tumors."

The manuscript published in Cells describes several studies elucidating UNO’s effect on both the adaptive and innate immune responses, as well as tumor responses, to a single administration of therapy. Specifically, in vitro studies showed that PD-L1 was upregulated in both CT26 and 4T1 tumor models following exposure to UNO, implying a possible mechanism for overcoming PD-1 resistance (Figure 1).

PD-L1 Upregulation in CT26 and 4T1 Cells after In Vitro Exposure to UNO

Intratumorally, UNO resulted in a substantial and enduring reduction in the T-reg/CD8+ ratio demonstrating a less tumorigenic microenvironment (Figure 2).

T-cell profiling in tumors of CT26 mice treated with UNO

Systemically, the acute effects of UNO treatment included a decrease in MDSC’s and simultaneous increase in M1 macrophages, demonstrating a more immunogenic blood profile (Figure 3).

Myeloid cell profiling in CT26 tumors treated with UNO

Figure 3: Myeloid cell profiling in CT26 tumors treated with UNO

"The publication of our second peer-reviewed manuscript in the journal Cells further demonstrates the acceptance of the science of UNO by an expanding community of researchers," said Dr. Selena Chaisson, Chief Executive Officer. "I am excited for the presentation of our initial clinical data at SITC (Free SITC Whitepaper)."

About Nitric Oxide
Nitric Oxide (NO) is a potent molecule, naturally synthesized in the human body, proven to play a critical role in a broad array of biological functions. In the airways, NO targets the vascular smooth muscle cells that surround the small resistance arteries in the lungs. Currently, exogenous inhaled NO is used in adult respiratory distress syndrome, post certain cardiac surgeries and persistent pulmonary hypertension of the newborn to treat hypoxemia. Additionally, NO is believed to play a key role in the innate immune system and in vitro studies suggest that NO possesses anti-microbial activity not only against common bacteria, including both gram-positive and gram-negative, but also against other diverse pathogens.

On October 17, 2023 GSK plc reported that it will present data at the ESMO (Free ESMO Whitepaper) Congress 2023 (20-24 October) focusing on Jemperli (dostarlimab) and Zejula (niraparib) that further demonstrate advancements in immuno-oncology and gynaecologic cancers and improving patient outcomes (Press release, GlaxoSmithKline, OCT 17, 2023, View Source [SID1234636078]).

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Advancing research for patients with NSCLC

GSK will share updates from the PERLA trial evaluating dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy in the first-line treatment of metastatic non-squamous NSCLC. Expanding upon the primary data presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2022, late-breaking results at ESMO (Free ESMO Whitepaper) 2023 (LBA64) will highlight a positive numerical trend in OS outcomes, favouring dostarlimab plus chemotherapy vs. pembrolizumab plus chemotherapy. The PERLA phase II trial is a randomised, double-blind trial of 243 patients and is the largest global head-to-head trial of programmed death receptor-1 (PD-1) inhibitors in this patient population.

In the PERLA trial, the median OS for patients receiving dostarlimab plus chemotherapy was 19.4 months (95% CI: 14.5-NR) versus 15.9 months (95% CI: 11.6-19.3) for patients receiving pembrolizumab plus chemotherapy, after a median follow-up of 20.7 months (17.3-24.0) and 21.6 months (18.3-24.1), respectively (HR: 0.75: [95% CI: 0.53-1.05]). An additional analysis with greater OS maturity is planned and will be reported at a later date. Safety profiles in this secondary analysis were similar and consistent with those previously reported in the primary analysis for the PERLA trial.

Data from PERLA supports the company’s ambition for dostarlimab to become its backbone immuno-oncology therapy when used alone and in combination with standard of care and future novel cancer therapies.

Updates from the RUBY clinical trial

GSK will also present updates from Part 1 of the phase III RUBY clinical trial evaluating dostarlimab in combination with chemotherapy compared to standard of care chemotherapy in patients with primary advanced or recurrent endometrial cancer. During a mini oral presentation (740MO), results from an exploratory analysis of the RUBY trial will show the effect of dostarlimab plus chemotherapy on PFS and OS across molecular classifications initially defined by The Cancer Genome Atlas, including mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H), no specific molecular profile (NSMP) and tumour protein 53 aberrant (TP53mut) subgroups.

In the analysis, PFS and OS results favoured patients treated with dostarlimab plus chemotherapy in the dMMR/MSI-H, TP53mut and NSMP subgroups, with the largest benefit observed in the dMMR and TP53mut groups. This exploratory analysis will provide insights into how molecular classification may help further the understanding of which patients are most likely to derive benefit from treatment.

GSK will also present results (750P) from the RUBY trial focusing on investigator-assessed progression-free survival 2 (PFS2). PFS2 is a secondary endpoint for the trial, defined as the time from treatment randomisation to progression on the first subsequent anticancer therapy following study treatment or death by any cause. The presentation will also include OS results after adjustment for subsequent use of immuno-therapy (dostarlimab, pembrolizumab, durvalumab, nivolumab or pembrolizumab with lenvatinib). The results show PFS benefits are sustained beyond first progression and further support the OS benefits in patients treated with dostarlimab plus chemotherapy vs. chemotherapy alone despite the use of subsequent therapies.

Safety profiles in both analyses were similar and consistent with those previously reported for the RUBY trial.

Exploring real-world experience with first-line maintenance therapy in ovarian cancer

Presentation of an analysis (789P) of real-world data of patients with epithelial ovarian cancer, obtained from a national United States electronic healthcare record-derived de-identified database, will shed new light on treatment duration and causes of discontinuation among individuals receiving niraparib in the first-line maintenance setting. The analysis found that patients with epithelial ovarian cancer who are taking first-line maintenance niraparib for more than 90 days have a longer time to treatment discontinuation than all other patients in the analysis. Findings will contribute to the understanding of effective clinical management of toxicity early in the maintenance period, which may help patients stay on treatment and experience the full therapeutic benefit of niraparib.

Collaborating to improve patient care

GSK is supporting investigator-sponsored studies and fostering scientific collaborations with both experienced investigators and networks, who are involved in the continuum of care of patients living with cancer. In addition to GSK’s presentations at ESMO (Free ESMO Whitepaper), there will be seven additional GSK-supported investigator-sponsored study presentations.

Full list of GSK’s presentations at ESMO (Free ESMO Whitepaper):

Abstract Name Presenter Presentation Details
Overall survival from a phase II randomised double-blind trial (PERLA) of dostarlimab (dostar) + chemotherapy (CT) vs pembrolizumab (pembro) + CT in metastatic non-squamous NSCLC S. Peters LBA64
Dostarlimab + chemotherapy for the treatment of primary advanced or recurrent endometrial cancer (pA/rEC): analysis of progression free survival (PFS) and overall survival (OS) outcomes by molecular classification in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial M. Mirza 740MO
PFS2 and adjustment of overall survival (OS) for subsequent anticancer therapy in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) treated with dostarlimab plus chemotherapy or chemotherapy alone in the ENGOT-EN3-NSGO/GOG-3031/RUBY trial B. Slomovitz 750P
Patient-reported outcomes (PROs) in patients (pts) with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer (pA/rEC) in the ENGOT-EN6-NSGO/GOG3031/RUBY trial G. Valabrega 749P
Real-world (RW) duration of treatment in first-line maintenance (1Lm) niraparib monotherapy in epithelial ovarian cancer (EOC): CHAR1ZMA study F. Backes 789P
Patients’ perspective on tolerability of dostarlimab in NSCLC: patient-reported outcomes from the phase II PERLA trial M. Reck 1468P
Full list of collaborative studies at ESMO (Free ESMO Whitepaper):

Abstract Name Presenter Presentation Details
Atezolizumab (atezo) combined with platinum-based chemotherapy (CT) and maintenance niraparib for recurrent ovarian cancer (rOC) with a platinum-free interval (TFIp) >6 months: Primary analysis of the double-blind placebo (pbo)-controlled ENGOT-Ov41/GEICO 69-O/ANITA phase 3 trial A. Gonzalez-Martin LBA37
Niraparib (NIRA) with abiraterone acetate plus prednisone (AAP) as first-line (1L) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Three-year update and final analysis (FA) of MAGNITUDE K. Chi LBA85
Patients with endometrial cancer: expectations and understanding of genetic counseling and hereditary carcinomas – first results of an international NOGGO/GCIG/ENGOT survey (EXPRESSION XI / IMPROVE) J. Sehouli 751P
Tolerability and effectiveness of niraparib in long-term responders with platinum-sensitive recurrent ovarian cancer (GEICO-88R study) J. Cueva 795P
Efficacy of niraparib and abiraterone acetate plus prednisone (NIRA+AAP) in homologous recombination repair gene-altered (HRR+) metastatic castration-resistant prostate cancer (mCRPC) by tissue and/or plasma assays in the MAGNITUDE trial G. Attard 1806P
A prospective study to determine the prevalence of DNA repair defects in patients (pts) with advanced prostate cancer (PC) S. Sandhu 1835P
PARPiPANC – A multicentric, single arm, phase II assessing niraparib as first line therapy for patients with metastatic homologous repair-deficient pancreatic cancer P. Cassier 1684TiP
About PERLA

The PERLA phase II trial is a global, randomised, double-blind trial of 243 patients evaluating the efficacy and safety of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy in patients with metastatic non-squamous NSCLC without a known sensitising epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation V600E mutation of the BRAF gene or other genomic mutation for which an approved targeted therapy is available. The primary endpoint is objective response rate of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy assessed by blinded independent central review per RECIST v1.1. Secondary endpoints include investigator-assessed progression-free survival per RECIST v1.1, overall survival, and safety.

About RUBY

RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

The dual-primary endpoints in Part 1 are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and ITT populations and OS in the overall population. Pre-specified exploratory analyses of PFS in the mismatch repair proficient (MMRp)/microsatellite stable (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, with OS as a key secondary endpoint. Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

About Jemperli (dostarlimab)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.[1]

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H), and as a single agent for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. The sBLA supporting the new indication in combination with carboplatin and paclitaxel received Breakthrough Therapy designation from the FDA. Jemperli is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these medicines under the agreement.

Important Information for Jemperli in the EU

Indication 

Jemperli is indicated as monotherapy for treating adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

Refer to the Jemperli EMA Reference Information for a full list of adverse events and the complete important safety information in the EU.