On March 17, 2024 Infinitopes reported the company collaborating with the leading mass spectrometry technology company Bruker to develop a world leading immunopeptidomic based antigen discovery platform (Press release, Infinitopes, MAR 17, 2024, View Source [SID1234648454]). In a recent poster, Infinitopes showcase their state-of-the-art sample preparation capabilities in synergy with the latest high-sensitivity mass spectrometry technology from Bruker. Building on Inifinitopes’ proprietary antigen purification strategy Bruker optimise the performance of their new timsTOF Ultra mass spectrometer providing a highly sensitive platform for antigen discovery. Bruker fine-tuned their instrument parameters to enable identification of thousands of peptide antigens from just 1 million melanoma cells. This development paves the way for cancer antigen discovery directly from patient biopsies, overcoming a critical unmet need for target discovery in the field of immuno-oncology. Dr. Rob Parker, Lead Scientist Discovery Immunomics of Infinitopes, commented:

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"We are excited to see our R&D capabilities drastically expanded through our unique collaboration with Bruker. Bruker’s commitment toward ultra-sensitive discovery immunopeptidomics will accelerate Infinitopes growth and provide unique benefit to our existing and future and partners, with our enhanced R&D output positioning Infinitopes as a leading force in cancer antigen discovery".

On March 17, 2024 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, reported patients in the AMPECT trial whose malignant perivascular epithelioid cell tumor (PEComa) had gynecologic origins experienced efficacy and safety consistent with the overall study population (Press release, Aadi Bioscience, MAR 17, 2024, View Source [SID1234641218]). The AMPECT trial formed the basis for the FDA approval of the company’s nab-sirolimus, FYARRO, for advanced malignant PEComa regardless of mutational status. This new subgroup analysis will be presented during an oral plenary at the Society of Gynecologic Oncology (SGO) Annual Meeting in San Diego, CA on March 17, 2024.

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"In AMPECT, advanced malignant PEComa tumors originating from uterine, ovarian, pelvic or retroperitoneal sites had a response to nab-sirolimus consistent with that of the full study population, including overall response rate, onset and duration of tumor response," said Thomas J. Herzog, MD, Deputy Director, University of Cincinnati Cancer Center. "Malignant PEComa tumors of gynecologic or retroperitoneal origin accounted for more than half of the evaluable patients enrolled, offering important insights into this population and reinforcing the need for awareness and understanding of this rare but aggressive cancer among the gynecologic oncologist community."

Oral plenary presentation details and study highlights include:

Title: "Response to Treatment with nab-Sirolimus in Patients with Perivascular Epithelioid Cell Sarcoma (PEComa) of Gynecologic or Retroperitoneal Origin: Subgroup Analysis from AMPECT"
Presenting Author: Thomas J. Herzog, MD
Session Title: Focused Plenary V: Rare Care: Updates in Uncommon Cancers
Location: Ballroom 20CD
Date/Time: Sunday, March 17, 2024 – 1:45 PM to 2:45 PM

Of the 31 patients enrolled in AMPECT, 16 had malignant PEComas originating from uterine, ovarian, pelvic or retroperitoneal sites
Overall response rate to nab-sirolimus for the subgroup was 37.5% (6/16), consistent with the overall AMPECT population
Subgroup responses were rapid and durable, with 1.4 months median time to response and 36.2 months median duration of response
Safety profile of the subgroup was manageable and consistent with the overall AMPECT population
Additional data presented at SGO further highlight nab-sirolimus as a potential approach for mTOR-driven gynecologic cancers. These presentations include a real-world study characterizing TSC1 and TSC2 inactivating alterations in patients with advanced gynecologic cancers; trial-in-progress updates for the ongoing, tumor agnostic, registration-intended PRECISION1 trial; and a Phase 2 study of nab-sirolimus in combination with letrozole for advanced or recurrent endometrioid-type endometrial cancer (EEC).

"Overactivation of the mTOR pathway has been implicated in gynecological cancers," said Loretta Itri, MD, Chief Medical Officer at Aadi. "nab-Sirolimus is a nanoparticle albumin-bound (nab) mTOR inhibitor under investigation in TSC1- and TSC2-mutated tumors as well as other mTOR-driven tumors. We are diligently continuing to explore the potential of nab-sirolimus for this patient community in need of new therapies."

Poster presentation details and highlights include:

Title: "Analysis of inactivating TSC1 and TSC2 alterations in a real-world patient population with advanced gynecological cancers in the Foundation Medicine genomic database"
Presenting Author: Lauren E. Dockery, MD, MS
Session Title: Poster Session 1
Location: Exhibit Hall (Hall GH)
Poster Number: 1176
Date/Time: Sunday, March 17, 2024 – 1:15 PM to 2:45 PM

Registration-directed PRECISION1 study is enrolling patients with solid tumors harboring TSC1 and/or TSC2 inactivating alterations
In a large real-world database of patients with advanced cancer, 1,342 (2.4%) of the 54,911 patients with gynecological cancers harbored at least one inactivating alteration in TSC1 or TSC2
TSC1 and/or TSC2 inactivating alterations were present in 3.6% of endometrial cancers, 2.0% of ovarian cancers and 1.5% of cervical cancers
Title: "nab-Sirolimus Plus Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer: A Phase 2, Open-Label, Single-Arm, Prospective, Multi-Center Study"
Presenting Author: Lauren E. Dockery, MD, MS
Session Title: Poster Session 2
Location: Exhibit Hall (Hall GH)
Poster Number: 2127
Date/Time: Monday, March 18, 2024 – 11:45 AM to 12:45 PM

This ongoing phase 2, open-label, single-arm, multicenter study is evaluating nab-sirolimus in combination with letrozole for the treatment of patients with advanced or recurrent EEC
Prior clinical studies with mTOR inhibitors and endocrine therapy have yielded promising results in EEC
Title: "nab-Sirolimus for Malignant Solid Tumors Harboring Pathogenic Inactivating Alterations in TSC1 and TSC2 in a Phase 2, Multicenter, Open-Label Tumor-Agnostic Trial: PRECISION 1"
Presenting Author: Debra L. Richardson, MD
Session Title: Poster Session 2
Location: Exhibit Hall (Hall GH)
Poster Number: 2126
Date/Time: Monday, March 18, 2024 – 11:45 AM to 12:45 PM

TSC1 and/or TSC2 inactivating alterations have been observed in patients with gynecological cancers with a frequency of up to 5.0% in endometrial cancer, 2.2% in ovarian cancer and 1.5% in cervical cancer

On March 16, 2024 Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, reported the results from two studies at the 2024 SGO Annual Meeting on Women’s Cancer (Press release, LabCorp, MAR 16, 2024, View Source [SID1234641217]). The studies demonstrate the value of biomarker testing in closing testing gaps and guiding targeted therapies for patients with epithelial ovarian cancer (EOC).

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With the rapid rate at which cancer biomarkers are being identified and new targeted therapies become available, comprehensive testing approaches are becoming even more critical as corresponding treatment guidelines evolve. Labcorp researchers conducted two studies to generate further evidence of the value of comprehensive genomic profiling to drive guideline-compliant testing that enables increased patient access to targeted therapies for improved outcomes.

Combination of BRCA testing with HRD Testing Needed to Inform Benefit of PARP Inhibitor Therapy
In one such study, conducted in partnership with Illumina, a leader in next-generation sequencing technologies, 1,093 patients diagnosed with EOC were evaluated to assess real-world clinical practice patterns for ordering BRCA and Homologous Recombination Deficiency (HRD) testing. When combined, the results of BRCA and HRD testing can determine which patients are most likely to benefit from treatment with poly-ADP ribose polymerase (PARP) inhibitors. For patients who test negative for BRCA1 and BRCA2, testing for HRD can help determine the degree of benefit from a PARP inhibitor.1

PARP inhibitors have transformed the standard of care, especially for women with germline or deleterious somatic mutations in BRCA1 or BRCA2.2 However, at least 40% of patients do not respond to PARP inhibitors, and if treated with PARP inhibitors, may experience longer treatment durations and potentially serious side effects,3 as well as increased overall costs. Treatment guidelines for PARP inhibitors emphasize the importance of diagnostic testing and individualized patient assessments.1

Within the study population, 84% of patients underwent evaluation for BRCA mutations or HRD testing; however, less than 50% of patients underwent HRD testing. Researchers then evaluated PARP inhibitor utilization and evaluated the time to treatment discontinuation (TTD) among patients with germline/somatic BRCA mutations, tumors with HRD, and those that were homologous recombination proficient (HRP). Patients with BRCA mutations4 or HRD[5] tend to do well on PARP inhibitors, so testing for each can help identify patients who may be most appropriate for PARP inhibitor maintenance.

Consistent with prior prospective clinical trials, researchers reported that the median TTD of first-line PARP inhibitor maintenance therapy was the longest for patients with germline or somatic BRCA mutations or HRD tumors. Among the study groups, 77% of the patients with a germline BRCA mutation, 65.1% of patients with a somatic BRCA mutation, and 42.7% of those with HRD and BRCA wild-type continued PARP inhibitor therapy at 18 months, compared to 29% of patients in the HRP/BRCA wild-type group.

"This research emphasizes the power of comprehensive biomarker testing in advancing the treatment of ovarian cancer. By closing critical diagnostic gaps through precision testing, we are not just improving patient care but also propelling science and healthcare forward," said Shakti Ramkissoon, M.D., Ph.D., vice president, head of oncology at Labcorp. "These findings affirm that access to advanced technology, in collaboration with partners with a shared commitment to the most current care models, is the cornerstone of developing innovative diagnostic tools. These new assays can offer more patients with access to effective, biomarker-guided therapies, ultimately leading to better prognoses and opening doors to new possibilities in gynecologic oncology."

The studies are among the growing body of evidence highlighting the value of biomarker testing for EOC, specifically in real-world settings. High-grade serous epithelial ovarian cancer (HGSOC) is the deadliest of all gynecological cancers, with 70% of patients having a cancer recurrence within two to three years and almost 50% dying from the disease after five years of diagnosis.

"This research highlights the need for additional healthcare provider education on comprehensive genomic approaches and the clinical utility of guideline-driven testing to improve patient care in ovarian cancer," said Pratheesh Sathyan, head of oncology for Americas region in medical affairs at Illumina.

High Folate-receptor Alpha (FOLR1/FRα) Expression Seen in Primary EOC Tumors
In another study, Labcorp researchers evaluated real-world testing practice patterns for Folate-receptor Alpha (FRα) on primary tumors versus metastatic tumors to guide targeted therapy for patients with platinum-resistant EOC. FRα is an actionable biomarker in ovarian cancer and is overexpressed in up to 90% of EOC patients.6 Patients with platinum-resistant EOC whose tumors highly express FRα may be eligible for treatment with Mirvetuximab soravtansine (MIRV), the only currently available targeted therapy that improves overall survival for patients with platinum-resistant EOC.

Researchers performed a retrospective analysis of tumor samples from 432 patients with EOC undergoing standard-of-care testing via the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay (developed by Roche). Of the tumor samples analyzed, 291 were from metastatic tumors, and 133 were from primary tumors. Researchers reported that 36.2% of patients had tumors that highly expressed FRα. In a critical study finding, tumor samples from primary sites were associated with higher rates of FRα positivity than those from metastatic sites.

"This study demonstrates not only the important role that FOLR1 testing can play in developing treatment strategies, but how it can help guide clinicians on the appropriate tumor sites to test to acquire the best information for that treatment guidance," said Ramkissoon.

On March 16, 2024 GSK plc (LSE/NYSE: GSK) reported statistically significant and clinically meaningful overall survival (OS) results from Part 1 and progression-free survival (PFS) results from Part 2 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial in adult patients with primary advanced or recurrent endometrial cancer. These data were presented today in a late-breaking plenary session at the Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer (16-18 March) (Press release, GlaxoSmithKline, MAR 16, 2024, View Source [SID1234641216]).

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The goal of the RUBY phase III trial programme is to evaluate which patients with primary advanced or recurrent endometrial cancer could potentially benefit from treatment with Jemperli (dostarlimab) plus chemotherapy, with or without the addition of Zejula (niraparib) maintenance. Part 1 of the RUBY phase III trial is investigating dostarlimab plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by dostarlimab compared to chemotherapy plus placebo followed by placebo. Part 2 of the RUBY phase III trial is evaluating dostarlimab plus standard-of-care chemotherapy, followed by dostarlimab plus niraparib as maintenance therapy compared to chemotherapy plus placebo followed by placebo. The safety and tolerability profiles of dostarlimab plus carboplatin-paclitaxel and dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib were generally consistent with the known safety profiles of the individual medicines.

Previous data showed a statistically significant and clinically meaningful improvement in PFS with Jemperli plus chemotherapy versus chemotherapy alone in frontline mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer. These data led to regulatory approvals for this patient population in the US, EU and certain other countries. Data presented today show additional potential benefit of dostarlimab plus chemotherapy, with or without the addition of niraparib, in the overall population of patients with primary advanced or recurrent endometrial cancer, including patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours, for which there are currently no approved immuno-therapy-based regimens.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK said: "The positive data presented today further show how dostarlimab-based regimens could benefit a broader set of patients with endometrial cancer. The results we’ve seen to date comprise the growing body of evidence supporting the role of dostarlimab as the backbone of our immuno-oncology development programme. Our goal is to continue to identify ways to use dostarlimab alone and in combination with other therapies to help improve outcomes for patients with limited treatment options."

RUBY Part 1: a statistically significant and clinically meaningful improvement in OS was observed for dostarlimab plus chemotherapy versus placebo plus chemotherapy, meeting a primary endpoint of the study.
Dostarlimab plus chemotherapy versus chemotherapy alone showed:

In the overall population:

a statistically significant reduction in the risk of death by 31% (Hazard Ratio [HR]: 0.69; [95% CI: 0.539–0.890])
a clinically meaningful improvement of 16.4 months in median OS (44.6 months vs 28.2 months)
In a prespecified exploratory analysis of the MMRp/MSS population:

a clinically meaningful trend in reduced risk of death by 21% (HR: 0.79; [95% CI: 0.602–1.044])
a clinically meaningful improvement of seven months in median OS (34.0 months vs 27.0 months)
Full OS summaries are shown below.

dostarlimab +
carboplatin-paclitaxel

placebo +
carboplatin-paclitaxel

Overall population, Number (N)

245

249

OS, HR (95% CI)

0.69 (0.539–0.890)

P-value1

0.002

OS, median (95% CI), mo.

44.6 (32.6–NR)

28.2 (22.1–35.6)

dMMR/MSI-H population2, N

53

65

OS, HR (95% CI)

0.32 (0.166–0.629)

OS, median3 (95% CI), mo.

NR (NR–NR)

31.4 (20.3–NR)

MMRp/MSS2, N

192

184

OS, HR (95% CI)

0.79 (0.602–1.044)

OS, median (95% CI), mo.

34.0 (28.6–NR)

27.0 (21.5–35.6)

1One-sided p-value based on stratified log-rank test.
2Exploratory analyses of OS in dMMR/MSI-H and OS in MMRp/MSS populations were pre-specified with no planned hypothesis testing.
3Although the median OS was not reached, at 30 months the estimated reduction in the risk of death was 82.8% for patients who received dostarlimab plus chemotherapy vs. 54.1% for patients who received chemotherapy alone.

Matthew Powell, MD, Division of Gynecologic Oncology, Washington University School of Medicine,
and US principal investigator of the RUBY trial said: "RUBY Part 1 is the first clinical trial to show a statistically significant and clinically meaningful improvement in overall survival for an immuno-oncology therapy in combination with chemotherapy in the overall population of patients with primary advanced or recurrent endometrial cancer. As a clinician, I celebrate the results of the RUBY Part 1 trial presented today, which show how dostarlimab added to chemotherapy could potentially benefit a broader set of patients with this type of cancer."

In RUBY Part 1, grade 3 or higher and serious treatment-emergent adverse events (AEs) were approximately 12% higher in the dostarlimab plus carboplatin-paclitaxel arm (treatment arm) compared with the placebo plus carboplatin-paclitaxel arm (control arm). The nature and types of immune-related AEs in the dostarlimab plus chemotherapy safety profile were consistent with the mechanism of action of dostarlimab and similar to those reported for other PD-(L)1 inhibitors. In the trial, 40.7% of participants in the treatment arm and 16.3% of participants in the control arm had immune-related AEs assessed by the investigator as related to dostarlimab or placebo, respectively. Discontinuation of dostarlimab or placebo due to a treatment-emergent AE occurred in 19.1% of patients in the treatment arm and 8.1% of patients in the control arm.

GSK expects US Food and Drug Administration regulatory submission acceptance based on RUBY Part 1 data for an expanded indication in the overall population in the first half of this year.

RUBY Part 2: addition of niraparib to dostarlimab in maintenance setting significantly improved PFS in first-line primary advanced or recurrent endometrial cancer compared to chemotherapy alone, meeting the primary endpoint of the trial.
Dostarlimab plus chemotherapy followed by dostarlimab plus niraparib compared to placebo plus chemotherapy followed by placebo showed:

In the overall population:

a statistically significant reduction in the risk of disease progression or death by 40% (HR: 0.60 [95% CI: 0.43–0.82])
a clinically meaningful improvement of 6.2 months in median PFS (14.5 months vs 8.3 months)
In the MMRp/MSS population:

a statistically significant reduction in the risk of disease progression or death by 37% (HR: 0.63 [95% CI: 0.44–0.91])
a clinically meaningful improvement of 6.0 months in median PFS (14.3 months vs 8.3 months)
Dr Mansoor Raza Mirza, Chief Oncologist, Copenhagen University Hospital, Denmark, and RUBY principal investigator said: "In RUBY Part 2, we observed that the use of dostarlimab in combination with niraparib in the maintenance therapy setting further improved progression-free survival versus placebo for patients with primary advanced or recurrent endometrial cancer. These findings are particularly important for patients who have MMRp/MSS tumours as the data help build on the initial benefit observed with an immuno-oncology plus chemotherapy regimen, reflecting the potential for the addition of niraparib maintenance to address unmet medical need for these patients."

In RUBY Part 2, grade 3 or higher and serious treatment-emergent AEs were approximately 36% and 24% higher, respectively, in the dostarlimab plus chemotherapy followed by dostarlimab plus niraparib arm (treatment arm) compared with the placebo plus chemotherapy followed by placebo arm (control arm). In the trial, 36.6% of participants in the treatment arm and 6.3% of participants in the control arm had immune-related AEs assessed by the investigator as related to dostarlimab or placebo, respectively. No cases of myelodysplastic syndrome/acute myeloid leukaemia were reported; other secondary primary malignancies occurred in 1 patient each in both treatment arms. Discontinuation of dostarlimab or placebo due to a TEAE occurred in 24.1% of patients in the treatment arm and 5.2% of patients in the control arm. Discontinuation of niraparib or placebo due to a treatment-emergent AE occurred in 15.7% of patients in the treatment arm and 4.2% of patients in the control arm.

About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries, with approximately 417,000 new cases reported each year worldwide1, and incidence rates are expected to rise by almost 40% between 2020 and 2040.2,3 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.4

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.

In Part 1, the dual-primary endpoints 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 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 organisation dedicated to transforming the standard of care in gynaecologic oncology.

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-L2.5

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 dMMR, as determined by a US FDA-approved test, or MSI-H, and as a single agent for adult patients with 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 supplemental Biologics License Application supporting the newly approved indication in combination with carboplatin and paclitaxel for dMMR/MSI-H primary advanced or recurrent endometrial cancer received Breakthrough Therapy designation and Priority Review from the US 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. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli, and cobolimab (GSK4069889), a TIM-3 antagonist.

Important Information for Jemperli in the EU
Indication 
Jemperli is indicated:

in combination with carboplatin-paclitaxel, for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;
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.

About Zejula (niraparib)
Zejula is an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor indicated in the US for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; and for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy and who have been selected based on a US FDA-approved companion diagnostic for Zejula.

Important Information for Zejula in the EU 
Indication
Zejula is indicated:

as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.
as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.
Refer to the Zejula EMA Reference Information for a full list of adverse events and the complete important safety information in the EU.

On March 15, 2024 CStone Pharmaceuticals (HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, reported that the China National Medical Products Administration (NMPA) has approved its new marketing application for Zygenix ( sugemalimab injection) in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma expressing PD-L1 (combined positive score [CPS] ≥5) (Press release, CStone Pharmaceauticals, MAR 15, 2024, View Source [SID1234656251]). Zygenix becomes the world’s first PD-L1 monoclonal antibody approved for this indication.

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Dr. Jianxin Yang, CEO of CStone Pharmaceuticals, said, "We are very pleased that Zegemet has been approved in combination with chemotherapy for the first-line treatment of gastric cancer patients in China. This further demonstrates the clinical value and potential of Zegemet . Zegemet has previously been approved in China for indications including stage III and IV non-small cell lung cancer, extranodal NK/T-cell lymphoma, and esophageal squamous cell carcinoma. With this, Zegemet has achieved a grand slam achievement of approval for all five target indications. We are currently in discussions with the U.S. Food and Drug Administration (FDA) regarding registration and marketing approval in the U.S., and will continue to communicate closely with global regulatory agencies such as the European Medicines Agency (EMA) to further advance Zegemet ‘s global registration and marketing. We look forward to Zegemet benefiting more cancer patients worldwide."

Professor Lin Shen from Peking University Cancer Hospital, Principal Investigator of the GEMSTONE -303 study of Zygen, said: "China is one of the countries with the heaviest burden of gastric cancer globally. Clinically, most gastric adenocarcinoma patients are already in the advanced stage at the time of initial diagnosis and cannot undergo surgical resection. The prognosis for patients with advanced or metastatic gastric cancer is generally poor, and there is a huge unmet medical need. Zygen is the first approved PD-L1 monoclonal antibody with a clear biomarker for gastric cancer, and will undoubtedly provide more options for the precision treatment of G/GEJ patients. We hope that Zygen can be put into clinical use as soon as possible, bringing new hope for treatment to more gastric cancer patients."

The approval of the new marketing application for Zegnimet for gastric cancer is based on the GEMSTONE-303 study, a multicenter, randomized, double-blind, placebo-controlled Phase III registration clinical trial designed to evaluate the efficacy and safety of Zegnimet in combination with oxaliplatin and capecitabine as a first-line treatment for patients with locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma whose tumors are unable to undergo surgical resection and whose PD-L1 expression is ≥5%. The primary endpoints of the trial are PFS and OS assessed by the investigator, and secondary endpoints include PFS assessed by a blinded independent central review committee (BICR) and objective response rate (ORR) and duration of response (DoR) assessed by the investigator. The study has achieved its pre-specified dual primary endpoints.

Previously, the results of the Phase III GEMSTONE-303 study of Zegma combined with chemotherapy as the first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma were selected as a late- breaking abstract (LBA) at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, and detailed data were announced in the form of an oral report.

The data presented at the 2023 ESMO (Free ESMO Whitepaper) Congress were based on the final analysis of PFS, with a cutoff date of August 6, 2022, and the final analysis of OS, with a cutoff date of July 9, 2023. The results showed that the GEMSTONE-303 study met its pre-specified co-primary endpoints. In patients with PD-L1 expression ≥5%, Zegma combined with chemotherapy significantly improved PFS and OS compared to placebo combined with chemotherapy , with the differences being statistically significant and clinically meaningful.

The key results are as follows:

The median PFS assessed by investigators in the Zegemet treatment group and the placebo group was 7.6 months vs. 6.1 months, with a hazard ratio (HR) of 0.66 (95% CI, 0.54-0.81), P<0.0001 .
The OS of the Zegemet treatment group and the placebo group was 15.6 months vs 12.6 months, with a hazard ratio (HR) of 0.75 (95% CI, 0.61-0.92), P=0.0060 .
Subgroup analysis showed that all pre-set subgroups, including PD-L1 expression status, showed clinical benefits.
The investigator-assessed ORR for the Zegemet treatment group and the placebo group was 68.6% vs 52.7%, and the median DoR was 6.9 months vs 4.6 months .
Zegemet combined with chemotherapy has good tolerability and safety, and no new safety risks have been found .

About Gastric Cancer

Gastric cancer is one of the most common cancers worldwide. According to GLOBOCAN 2020 data, there were over 1 million new cases of gastric cancer and 769,000 deaths worldwide in 2020, making it the fifth most common cancer and the fourth leading cause of cancer death. China is one of the countries with the heaviest burden of gastric cancer, accounting for nearly half of the global number of new cases and deaths each year. Gastric adenocarcinoma accounts for over 90% of gastric malignancies, and the incidence of gastroesophageal junction adenocarcinoma has also been increasing in recent years.

About Zegemet ( sugemalimab injection)

Zegemet is an anti-PD-L1 monoclonal antibody developed by CStone Pharmaceuticals. Its development is based on the OmniRat transgenic animal platform, licensed from US-based Ligand Corporation . This platform enables the one-stop production of fully human antibodies. As a fully human, full-length anti-PD-L1 monoclonal antibody, Zegemet is the closest to the natural G-type immunoglobulin 4 (IgG4) response in the human body. Zegemet offers a lower risk of immunogenicity and related toxicities in patients, giving it a distinct advantage over similar drugs.

Currently, China’s NMPA has approved five indications for Zegemet :

First-line treatment in combination with chemotherapy for patients with metastatic squamous and non-squamous non-small cell lung cancer (NSCLC);
For the treatment of patients with unresectable, stage III non-small cell lung cancer who have not experienced disease progression after concurrent or sequential chemoradiotherapy;
Treatment of patients with relapsed or refractory extranodal NK/T-cell lymphoma;
First-line treatment in combination with fluoropyrimidine and platinum chemotherapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma; and
In combination with fluorouracil-containing and platinum-based chemotherapy, it is used for the first-line treatment of unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma that expresses PD-L1 (combined positive score [CPS] ≥ 5).
In addition, both the European Medicines Agency (EMA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have accepted marketing authorization applications for sugemalimab combined with chemotherapy for the first-line treatment of metastatic NSCLC. Both applications are currently under review.

CStone Pharmaceuticals and Pfizer have reached a strategic collaboration, including a strategic collaboration between CStone Pharmaceuticals and Pfizer Investment on the development and commercialization of Zegemet in mainland China, and a collaboration framework between CStone Pharmaceuticals and Pfizer Investment to introduce more oncology products into Greater China.