On May 26, 2022 Invitae (NYSE: NVTA), a leading medical genetics company, reported eight studies to be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in Chicago from June 3-7, 2022 (Press release, Invitae, MAY 26, 2022, View Source [SID1234615158]). While the research covers a variety of cancer types, stages and patient demographics, all of the data underscore the importance of universal genetic testing to improve health outcomes for all cancer patients.

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

Inherited genes impact risk for developing melanoma

Melanoma—the most frequent cause of skin cancer-related deaths—is often perceived as a cancer caused by environmental factors. While sun exposure plays a role in most melanoma tumors, a new, first-of-its-kind study by Cleveland Clinic and Invitae found that genetics also play a critical role in the likelihood of developing melanoma. In fact, the study found that 15% of individuals with melanoma have inherited variants in a variety of genes associated with cancer predisposition syndromes, demonstrating multiple potential etiologies. What’s more, genes previously associated with inherited melanoma comprised less than half of pathogenic variants (48%); and the majority of germline variants were in cancer predisposition genes that are not traditionally associated with melanoma. This study shows that all patients with melanoma should undergo genetic testing, whether or not they have a family history of cancer, or a personal history of sun exposure.

"Previously, it was thought that few melanoma patients would demonstrate a pathogenic germline variant in cancer susceptibility genes indicating an inherited component to their melanoma risk," said Joshua Arbesman, M.D., dermatologist at Cleveland Clinic and senior author of the study. "Our results, however, suggest that about 1 in 6 melanoma patients would have an inherited variant in cancer genes. This means that these particular patients would benefit from cancer specific screening (separate from skin screening) that could catch other cancers earlier. We found similar results using multiple datasets with variable inclusion criteria, suggesting this may be potentially applicable to many melanoma patients."

Research shows prostate cancer testing guidelines out of date

A separate study of prostate cancer patients confirmed similar findings that limiting genetic testing to those patients who meet NCCN guidelines deprives individuals and clinicians of actionable information. In data from the ongoing PROCLAIM study, conducted primarily in community urology clinics, 50% of pathogenic variants in patients with prostate cancer would be missed if genetic testing were done based on NCCN guidelines. The study also showed current guidelines are poorly suited to detect pathogenic variants in traditionally underrepresented populations, suggesting a transition to universal testing may be the most expeditious strategy to mitigate this potential healthcare disparity. Appropriately, patients with cancer-linked pathogenic variants in the study were more likely to have recommendations made by their clinicians regarding changes to treatment, follow up and cascade testing than those with negative or uncertain results. Clinicians made genetics-based recommendations across the spectrum of patients tested, including those not meeting NCCN criteria, and those with low-grade and non-metastatic disease.

"Guidelines from national and international oncologic societies are regularly updated but not always as quickly as our understanding of gene-disease relationships in the rapidly evolving field of genomic sequencing, and thus there are real world implications affecting patient-physician decision making as well as patient access to affordable and geographically accessible genetic testing," said Dr. Neal Shore, lead author of the study. "This study shows that germline genetic testing has a significant impact on prostate cancer patient care, and that urologists, oncologists, their patients and patients’ family members would benefit from making germline genetic testing a routine practice for all prostate cancer patients."

Genetic changes impact colorectal cancer care

In a third study of more than 34,000 colorectal cancer patients—the largest study of its kind to date—researchers found that 13% of patients had inherited pathogenic variants that could potentially impact patient eligibility for precision therapy, access to clinical trials and/or inform screening for future cancers. This study, in collaboration with investigators at the University of Pennsylvania Perelman School of Medicine, showed rates > 7.8% of clinically actionable pathogenic gene variants independent of age group, racial/ethnic group and panel size. The study saw a lower rate of pathogenic variants in known cancer genes in Hispanic patients and a higher rate of variants of uncertain significance (VUS) in Black, Asian and Hispanic patients. This underscores the historical underrepresentation of these patients in genetics studies, and the ongoing need to mitigate the associated healthcare disparities.

"In the United States, colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined," said Ed Esplin, M.D., Ph.D., FACMG, FACP, clinical geneticist at Invitae. "The genetic variants we inherit play a crucial role in providing patients access to approved precision therapies and clinical trials for colorectal cancer treatment, and to quantify and mitigate the risk of colorectal cancer in their at-risk family members. This study shows the importance of broadening genetic testing criteria to include all patients with colorectal cancer, regardless of age, race/ethnicity or family history."

Additional clinical research from Invitae at ASCO (Free ASCO Whitepaper)

Invitae is presenting additional research at ASCO (Free ASCO Whitepaper) in collaboration with academic institutions and research partners that showcase the importance of genetic testing to guide cancer diagnosis and precision medicine treatment. This effort is consistent with the primary objectives of the Cancer Moonshot to reduce the death rate from cancer by 50 percent and improve the experience of people and their families living with cancer. All of the presentations highlight Invitae’s commitment to improving the adoption of germline genetic testing among physicians and people living with cancer, highlighting the impact of cancer genetics on cancer patients from underserved populations, and effectively illustrating its clinical utility in improving patient care.

2022 ASCO (Free ASCO Whitepaper) presentations:

Poster 60/Abstract 4569: Titled: Germline variants across self-reported racial populations with urothelial carcinoma (UC). Presenter: Amin Nassar, M.D. — Saturday, June 4, 2022 at 1:15 p.m. CDT.
Abstract 10500: Titled: Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making. Presenter: Neal D. Shore, M.D. — Monday, June 6, 2022 at 8:00 a.m. CDT.
Abstract 10504: Titled: Clinical implications of germline genetic testing stratified by ethnicity in a large colorectal cancer cohort. Presenter: Sarah Coughlin, M.D. — Monday, June 6, 2022 at 8:00 a.m. CDT.
Poster 464/Abstract 10589: Titled: Integrated germline and somatic cancer testing provides opportunity to identify cancer risk and resolve variant origins. Presenter: King Das, M.D. — Monday, June 6, 2022 at 1:15 p.m. CDT.
Poster 455/Abstract 10580: Titled: Implementation of universal, pan-cancer germline genetic testing in cancer patients in Jordan. Presenter: Hikmat Abdel-Razeq, M.D. — Monday, June 6, 2022 at 1:15 p.m. CDT.
Poster 463/Abstract 10588: Titled: Universal genetic testing versus guideline-directed testing for hereditary cancer syndromes among traditionally underrepresented patients in a community oncology program. Presenter: Jeremy Clifton Jones, M.D. — Monday, June 6, 2022 at 1:15 p.m. CDT.
Poster 401/Abstract 10523: Titled: Germline predisposition in oncologic and dermatologic melanoma cohorts. Presenter: Pauline Funchain, M.D. — Monday, June 6, 2022 at 4:30 p.m. CDT.
Online Publication: Titled: Patterns and prevalence of pathogenic germline mutations using multi-gene panel testing in patients with ovarian cancer. The Jordanian Exploratory Cancer Genetics (Jo-ECAG) ovarian study. Lead Author Hikmat Abdel-Razeq, M.D.

On May 26, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of new clinical data on SRF388, a potential first-in-class IL-27 antibody (Press release, Surface Oncology, MAY 26, 2022, View Source [SID1234615157]). Data from the Phase 1/1b clinical trial of SRF388 as a monotherapy and in combination with pembrolizumab, Merck’s anti-PD-1 therapy, will be presented in an oral abstract session at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"In the ongoing SRF388 Phase 1 trial, we observed three confirmed partial responses across three different indications with multiple other patients experiencing durable clinical benefit in the form of disease stabilization," said Alison O’Neill, M.D., chief medical officer at Surface Oncology. "While still early, these findings are compelling and support our view that SRF388 holds exciting potential in the treatment of a variety of tumor types, particularly in combination with other immuno-oncology therapies."

"SRF388 is a potential first-in-class cytokine antagonist with a unique mechanism of anti-tumor activity that is showing encouraging early efficacy with a favorable safety and tolerability profile even in heavily pre-treated patients," added Aung Naing, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. "The biology of the pathway, strong preclinical data, and tolerability of SRF388 support the potential for IL-27 blockade to complement PD-1 inhibition and other standard-of-care therapies across a range of cancers."

SRF388 Data Highlights:

Confirmed partial responses (PR) were observed in two patients who received SRF388 monotherapy treatment: one in non-small-cell lung cancer (NSCLC) (previously reported) and one in clear cell renal cell carcinoma (RCC). In addition, a PR was observed in a patient who was treated with SRF388 in combination with pembrolizumab for hepatocellular carcinoma (HCC). The patient with HCC was refractory to two prior VEGFR TKIs, while the patients with NSCLC and RCC had both progressed on prior anti-PD-(L)1 therapy.
SRF388 was well tolerated at all doses investigated (up to 20 mg/kg), with no dose-limiting toxicity or high-grade safety signals observed.
Encouraging pharmacodynamic data demonstrated that, after SRF388 administration, circulating IFNg increased —an on-target mechanism of action indicating increased immune activation.
Based on these efficacy data, the criteria for opening Stage 2 of the RCC monotherapy cohort was met. SRF388 is also being evaluated in NSCLC as a monotherapy and in combination with pembrolizumab, as well as in triplet therapy with atezolizumab and bevacizumab in first-line HCC.
SRF388 Clinical Program Updates:

Surface will initiate a new Simon two-stage expansion study of SRF388 in combination with pembrolizumab in up to 40 patients with relapsed/refractory NSCLC.
Data from multiple SRF388 cohorts, including in NSCLC and first-line HCC, are anticipated in the first half of 2023.
ASCO Presentation Details:

Title: First-in-human study of SRF388, a first-in-class IL-27 targeting antibody, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors
Abstract: 2501
Session Type/Title: Oral abstract session / Developmental Therapeutics – Immunotherapy
Session Date and Time: Saturday, June 4, 2022, 1:15 p.m. – 4:15 p.m. CDT
Slides from the ASCO (Free ASCO Whitepaper) presentation will be posted on the Surface Oncology website following the conclusion of the session.

About SRF388
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver, kidney and lung cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA.

On May 26, 2022 Advaxis, Inc. (OTCQX: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported the publication of updated results from the clinical trial of the lead asset from its ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program (Press release, Advaxis, MAY 26, 2022, View Source [SID1234615156]).

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These results from the clinical study ADXS-503-101 evaluating the ADXS-503 construct, which is designed to target certain cancers’ commonly occurring hotspot mutations and other tumor-associated antigens, will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting to be held on June 4-7, 2022, along with the trial design of the study of the second construct from the ADXS-HOT program, ADXS-504.

The goals of this Phase 1/2 open-label trial are to evaluate safety, tolerability, antitumor activity and immune-correlative data of ADXS-503 administered in combination with KEYTRUDA in patients with metastatic NSCLC. In Part B of this study, ADXS-503 is added-on to KEYTRUDA within 12 weeks of the first scan showing disease progression following treatment with KEYTRUDA. In Part C, both drugs are administered to previously untreated patients. The study design of the Phase 1 investigator-sponsor study of ADXS-504 for patients with biochemically recurrent prostate cancer at Columbia University, Herbert Irving Comprehensive Cancer Center NYC, will also be presented.

Key presentation highlights:

Poster Title: "A phase 2 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non-small-cell lung cancer either progressing on prior pembrolizumab or in the first-line setting"
Presenter: Gregory J. Gerstner, M.D., Illinois Cancer Care
Session Type: Poster Session – Hall A
Session Title: "Lung Cancer—Non-Small Cell Metastatic"
Date and Time: June 6, 2022, 8-11 AM (CDT)

Key study characteristics and takeaways:

Part B: 14 patients failing pembrolizumab as last therapy have been treated with ADXS-503 + pembrolizumab (Dose Level 1) with all patients evaluable for safety and efficacy
Overall response rate (ORR) was 14% (2/14) and Disease Control Rate (DCR) was 36% (5/14)
Two durable partial responses (PR) sustained for over 9 months and 21 months, respectively
Three durable cases of stable disease (SD) lasting for over 3, 5 and 14 months, respectively
Patients who seem to achieve clinical benefit in Part B of the study include those with PD-L1 expression ≥ 50% and those with prior pembrolizumab monotherapy exposure ≥ 12 months and/or with DCR > 6 months
Part C: 3 patients have received ADXS-503 + pembrolizumab in the 1st-line metastatic setting with all patients evaluable for safety and efficacy
Data continue to show a DCR of 67% (2/3) in the first three evaluable patients in Part C
Poster Title: "Immunogenicity and disease control induced by a multi-neoantigen vaccine (ADXS-503) in patients with metastatic non-small-cell lung cancer who have progressed on pembrolizumab"

Presenter: Dr. Aaron E. Lisberg, M.D., UCLA
Session Type: Poster Session – Hall A
Session Title: "Lung Cancer—Non-Small Cell Metastatic"
Date and Time: June 6, 2022, 8-11 AM (CDT)

Key takeaways: Long-term follow up of immune correlative markers suggest that ADXS-503 leads to durable clinical benefit in select patients through:

the production of cytokines with periodic pro-inflammatory and anti-tumoral effects supporting innate and adaptive immunity
the activation of Natural Killer (NK) cells in tumor control
the induction of proliferation and activation of previously exhausted CD8+ T-cells facilitating reaction to hotspot mutation antigens, tumor associated antigens (TAAs), and antigen spreading.
The activation of various subsets of memory CD8+ T cells
Poster Title: "A phase I study of ADXS-504, a cancer type specific immunotherapy, for patients with biochemically recurrent prostate cancer"

Presenter: Karie Runcie, M.D., Columbia University
Session Type: Poster Session – Hall A
Session Title: "Trials in Progress"
Abstract Number: TPS5115
Date and Time: June 6, 2022, 1:15-4:15 CDT (CDT)

"The correlation of durable clinical benefit with long-term immunological surveillance data from Part B of the ADXS-503 study is extremely encouraging," said Ken Berlin, President and CEO of Advaxis. "We not only observe a competitive ORR by adding-on ADXS-503 in patients failing pembrolizumab, but we also now better understand how ADXS-503 may reverse the exhaustion or enhance the activity of pembrolizumab in these cases," he concluded. "The immunogenicity studies tend to demonstrate that ADXS-503 does more than just activate antigen-specific T cells as part of the adaptive response in Part B patients. The clinical benefit may also be derived from the serial elevation of certain serum cytokines throughout the course of therapy as well as from the activation of NK and induction of memory T cells. These pleotropic effects of Lm vectors, which had been documented in preclinical models and now shown in the ADXS-503 trial, help to differentiate ADXS-503 from other vaccine platforms," added Andres Gutierrez, EVP and Chief Medical Officer of Advaxis. "Importantly, those effects are induced safely and without the use of adjuvant agents," he concluded.

Enrollment in Part B will continue up to a total of 18 patients to further evaluate if ADXS-503 is able to achieve ORR of ≥20% in patients progressing on pembrolizumab therapy, while Part C may enroll up to 25 patients.

On May 26, 2022 Elevar Therapeutics, Inc., a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, reported its Phase 2 clinical trial (Study RM-202) evaluating rivoceranib, an orally administered tyrosine kinase inhibitor (TKI), demonstrated clinical effectiveness in patients with progressive recurrent or metastatic adenoid cystic carcinoma (R/M ACC) (Press release, Elevar Therapeutics, MAY 26, 2022, View Source [SID1234615155]). Elevar will present topline findings at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s annual meeting on June 6.

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This open-label study (NCT04119453) was conducted at 11 sites in the U.S. and South Korea to investigate the efficacy and safety of rivoceranib in patients with progressive R/M ACC, more than half of whom had received prior systemic therapy. Rivoceranib demonstrated meaningful results, with an overall response rate (ORR) of 15.1%, median duration of response (DoR) of 14.9 months, median progression-free survival (PFS) of 9 months and disease control for ≥3 months in over 60% of patients, regardless of prior vascular endothelial growth factor (VEGFR) therapy.

"Elevar is extremely pleased to share topline results of Study RM-202, which demonstrate that rivoceranib represents a potential new treatment option for patients with R/M ACC, who have a high unmet medical need," said Saeho Chong, chief executive officer of Elevar. "This pivotal study succeeded in demonstrating overall survival benefit and PFS in ACC via rivoceranib. It is also gratifying that rivoceranib demonstrates a favorable safety profile, reflecting adverse events consistent with other VEGFR TKIs.

"Following last week’s release, with partner Luzsana (formerly Hengrui Pharma), of positive Phase 3 hepatocellular carcinoma (HCC) data, we look forward to advancing rivoceranib through the regulatory process as an important option for the treatment of both ACC and HCC. Elevar looks forward to further discussing these noteworthy trial results with our esteemed peers at ASCO (Free ASCO Whitepaper)."

ASCO will be held June 3-7 at McCormick Place in Chicago, and online. Details of Elevar’s poster presentation are as follows:

With 80 patients, including 53 (66.3%) based in the U.S., Study RM-202 is the largest to date involving a TKI in ACC patients and the first to require progression within 6 months prior to the trial. Rivoceranib, which has been given orphan drug designation in the U.S., is an orally administered small molecule anti-angiogenic, with more than 6,000 patients studied in multiple cancers. Elevar has worldwide commercialization rights for rivoceranib, excluding China.

About ACC

Adenoid Cystic Carcinoma (ACC) is a rare malignancy that occurs within the secretory glands, most commonly in the major and minor salivary glands of the head and neck, but also found in the breast, skin and elsewhere. It is diagnosed in about 4 of every 1 million people each year – representing a combined 3,100 annual cases in the U.S., EU and Japan – and it afflicts more than 200,000 patients throughout the world, accounting for 5 percent to 7 percent of all head and neck malignancies, according to the Adenoid Cystic Carcinoma Research Foundation. There is no approved standard of care for R/M ACC patients. A previous study showed a baseline progression-free survival (PFS) of 2.8 months for ACC (Kang EJ, et al. Clin Cancer Res. 2021;27:5272-5279).

About Rivoceranib

Rivoceranib is the first small-molecule tyrosine kinase inhibitor (TKI) to be approved in gastric cancer in China (December 2014). Rivoceranib is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib, co-developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd. (JHP) in China and Elevar Therapeutics globally, with the exception of China. It has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy.

Clinical studies are underway in multiple tumor types including gastric cancer (as a monotherapy and in combination with paclitaxel), hepatocellular carcinoma (combination with camrelizumab), adenoid cystic carcinoma and colorectal cancer (combination with Lonsurf). Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), adenoid cystic carcinoma (U.S.) and hepatocellular carcinoma (U.S.). Elevar holds the global rights (excluding China) and has partnered for the development and marketing of rivoceranib with HLB-LS in South Korea. Apatinib is currently approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, JHP, under the brand name Aitan.

On May 26, 2022 GSK plc reported that it will present 25 abstracts at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (3-7 June) and nine abstracts at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress (9-12 June) focusing on approved therapies, Blenrep (belantamab mafodotin), Jemperli (dostarlimab) and Zejula (niraparib), as well as its investigational medicines (Press release, GlaxoSmithKline, MAY 26, 2022, View Source [SID1234615154]). The data presentations further demonstrate the company’s commitment to evaluate its approved and investigational therapies alone and in combination with other treatments and explore potential opportunities to improve patient care.

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Hesham Abdullah, SVP, Global Head of Oncology Development, GSK said: "We have strategically built a portfolio and pipeline that leverages the science of the immune system, human genetics and advanced technologies to address a variety of tumour types. The data we will be sharing at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) demonstrate how we’re delivering on our commitment to patients through novel approaches in some of the most promising areas of oncology research. We look forward to these important opportunities to come together and to share meaningful scientific updates with the broader oncology community."

Updates from the robust DREAMM clinical trial programme
Key presentations at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) include updates from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial programme evaluating belantamab mafodotin, an anti-BCMA (B-cell maturation antigen) therapy, in combination with both standard of care and investigational agents in earlier lines of therapy. Preliminary data from DREAMM-5 sub-study 3 of low-dose belantamab mafodotin in combination with nirogacestat in patients with relapsed/refractory multiple myeloma (ASCO abstract #8019) will be reported. Nirogacestat, an investigational gamma secretase inhibitor, has been shown to increase target density and reduce levels of soluble BCMA, and as such the potential to enhance the activity of BCMA-targeted therapies like belantamab mafodotin is under investigation.[i]

DREAMM-6 updates report outcomes from several dose cohorts of belantamab mafodotin in combination with lenalidomide and dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma who have received one or more prior lines of treatment (ASCO abstract #8017).

DREAMM-9, evaluating a quadruplet combination treatment regimen of belantamab mafodotin with standard of care (bortezomib, lenalidomide and dexamethasone or VRd) in patients with newly diagnosed multiple myeloma who are transplant ineligible, will also be presented at EHA (Free EHA Whitepaper) (EHA abstract #P942).

Collectively, the data from these trials are evaluating the efficacy and safety of belantamab mafodotin in patients with various lines of therapy, but also aim to assess how dose, scheduling and combination treatment may help to reduce corneal events associated with treatment. These data will be used to help inform further studies evaluating the potential of belantamab mafodotin in the multiple myeloma setting.

Blenrep received accelerated and conditional approvals in the US and EU, respectively, for adult patients with relapsed/refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 antibody, a proteasome inhibitor and an immunomodulatory agent. Studies are ongoing to verify clinical benefit.

Advancing research for patients with mismatch repair-deficient solid cancers
Results from the GARNET trial Cohorts A1 and A2 of dostarlimab, a programmed cell death receptor-1 (PD-1) blocking antibody, in advanced/recurrent (A/R) mismatch repair deficient/microsatellite instability-high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer will be presented during a presentation at ASCO (Free ASCO Whitepaper) (ASCO abstract #5509). These results include the largest cohort of patients with dMMR A/R endometrial cancer treated with a PD-1 inhibitor monotherapy and will inform long-term use of dostarlimab in this patient population. In addition, long-term outcomes from the GARNET trial Cohorts A1 and F will be shared, covering the efficacy and safety profile of dostarlimab in certain patients with dMMR recurrent or advanced solid tumours, including endometrial cancer (ASCO abstract #2587). Results from Cohort A1 of the GARNET trial served as the basis for conditional approval in the EU for the treatment of certain patients with dMMR/MSI-H recurrent or advanced endometrial cancer, and for the accelerated approval in the US for certain patients with dMMR recurrent or advanced endometrial cancer. Additionally, results from Cohorts A1 and F served as the basis for the accelerated approval in the US for certain patients with dMMR recurrent or advanced solid tumours.

Realising the potential of synthetic lethality
GSK will also present real-world analyses from six studies in patients with advanced ovarian cancer at ASCO (Free ASCO Whitepaper), including real-world data evaluating outcomes in patients with advanced ovarian cancer who receive poly (ADP-ribose) polymerase (PARP) inhibitor monotherapy as maintenance compared to those who do not. Insights from the presentations will deepen the understanding of the use of PARP inhibitors for maintenance therapy in advanced ovarian cancer and shed light on differences in treatment practice across geographic locations.

Separately, a phase III PRIME study update will be shared by Zai Lab (a GSK partner) evaluating niraparib (independently manufactured by Zai Lab) in Chinese patients with newly diagnosed advanced ovarian cancer using an individualised starting dose in a poster presentation (ASCO abstract #5551).

Continued research on immuno-oncology investigational agents
GSK will also present findings from its early-stage pipeline assets, including a poster discussion on the AMBER study evaluating cobolimab, an investigational anti-TIM-3 targeting monoclonal antibody, in combination with dostarlimab in patients with advanced or metastatic melanoma (ASCO abstract #9513). TIM-3 is a key immune checkpoint and a novel immuno-oncology target that could play a critical role in the treatment of solid tumours. GSK is evaluating cobolimab for patients with different tumour types through various novel combinations, including doublets and triplets.

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. At ASCO (Free ASCO Whitepaper), updated data from an investigator-sponsored study from Memorial Sloan Kettering Cancer Center will be featured in a late-breaking oral presentation entitled "Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer" (ASCO abstract #LBA5). Initial data were presented earlier this year at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI). There will be five additional GSK-supported investigator-sponsored studies presented at ASCO (Free ASCO Whitepaper).

At EHA (Free EHA Whitepaper), data from the BelaCarD investigator-sponsored study will report safety, tolerability and preliminary efficacy of belantamab mafodotin in combination with carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma (EHA abstract #P946). Additionally, an oral presentation on updated results from a supported collaborative study will evaluate the safety and efficacy of belantamab mafodotin plus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma (EHA abstract #S178).

Full list of GSK’s presentations at ASCO (Free ASCO Whitepaper):
Dostarlimab
Abstract Name

Presenter

Presentation Details

Comparison of Survival Outcomes Between Dostarlimab and Comparator Treatments (tx) in Patients (pts) with Advanced/Recurrent (A/R) Endometrial Cancer (EC) in England: Matching-Adjusted Indirect Comparisons (MAICs)

S. Goulden

Online publication, #e17534

Dostarlimab in Advanced/Recurrent (AR) Mismatch Repair Deficient/Microsatellite Instability–High or Proficient/Stable (dMMR/MSI-H or MMRp/MSS) Endometrial Cancer (EC): The GARNET Study

A. Oaknin

Clinical Science Symposium presentation, #5509

Efficacy and Safety of Dostarlimab in Patients (pts) with Mismatch Repair Deficient (dMMR) Solid Tumors: Analysis of 2 Cohorts in the GARNET Study

T. André

Poster presentation, #2587

Patient-Reported Outcomes from the GARNET Trial in Patients with Advanced or Recurrent Mismatch Repair Deficient (dMMR) Colorectal Cancer (CRC): A Post Hoc Subgroup Analysis

J. Hanlon

Poster presentation, #3558

Survival Outcomes for Dostarlimab and Real-World (RW) Treatment (tx) Paradigms in Post-Platinum Patients (pts) with Advanced/Recurrent (A/R) Endometrial Cancer (EC): The GARNET Trial versus an External Control Arm from the Flatiron Health Database

R. Coleman

Poster presentation, #5593

Understanding Patient Characteristics, Treatment Patterns, and Clinical Outcomes for Advanced and Recurrent Endometrial Cancer in Alberta, Canada

J. McGee

Online publication, #e17624

Belantamab Mafodotin
Abstract Name

Presenter

Abstract Number

Exploring Alternative Dosing Regimens of Single-Agent Belantamab Mafodotin on Safety and Efficacy in Patients with Relapsed or Refractory Multiple Myeloma: DREAMM-14

M. Hultcrantz

Poster presentation, #TPS8073

Safety and Clinical Activity of Belantamab Mafodotin with Lenalidomide Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-6 Arm-A Interim Analysis

H. Quach

Poster discussion, #8017

Safety and Clinical Activity of Belantamab Mafodotin with Pembrolizumab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-4 Study

A. Suvannasankha

Poster discussion, #8018

Synergistic Effects of Low-Dose Belantamab Mafodotin in Combination with a Gamma-Secretase Inhibitor (Nirogacestat) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-5 Study

S. Lonial

Poster discussion, #8019

Niraparib
Abstract Name

Presenter

Presentation Details

MOONSTONE/GOG-3032: Interim Analysis of a Phase 2 Study of Niraparib + Dostarlimab in Patients (pts) with Platinum-Resistant Ovarian Cancer (PROC)

L. Randall

Poster presentation, #5573

Real-World Trends of PARPi Maintenance Treatment Uptake and Progression-Free Survival (PFS) in Patients (Pts) with Newly Diagnosed Advanced Ovarian Cancer (AOC) in the United States

J. Chan

Poster presentation, #6580

Treatment and Outcome of Patients with High Grade Advanced Ovarian Cancer (AOC) – Real World Data in Germany (QS Ovar of the AGO Study Group)

S. Mahner

Online publication, #e17613

Treatment Patterns and Time to Next Treatment Among Patients with OC in a Real-Life Setting in Finland: The OCRWE-Finland Study

H. Rauhamaa

Online publication, #e18806

Pipeline
Abstract Name

Presenter

Presentation Details

AMBER Parts 1C and 1E: A Phase 1 Study of Cobolimab plus Dostarlimab in Patients (pts) with Advanced/Metastatic Melanoma

A. Ribas

Poster discussion, #9513

Phase 1 Trial of TIM-3 Inhibitor Cobolimab Monotherapy and in Combination with PD-1 Inhibitors Nivolumab or Dostarlimab (AMBER)

G. Falchook

Oral presentation, #2504

Primary Efficacy and Safety of Letetresgene Autoleucel (lete-cel; GSK3377794) Pilot Study in Patients with Advanced and Metastatic Myxoid/Round Cell Liposarcoma (MRCLS)

S. D’Angelo

Oral presentation, #11500

Study Design of A Global Molecular Disease Characterization Initiative (MDCI) in Oncology Clinical Trials

D. Downs

Online publication, #e13598

ZENYTH-ESO: Master Protocol to Assess the Safety and Recommended Phase II Dose of Next Generation NY-ESO-1–Specific TCR T-cells in HLA-A*02 Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma [Substudy 3, GSK4427296]

D. Araujo

Poster presentation, #TPS2681

Full list of investigator-sponsored studies at ASCO (Free ASCO Whitepaper):
Abstract Name

Presenter

Presentation Details

AGO-OVAR 28 / ENGOT-ov57: Niraparib vs Niraparib in Combination with Bevacizumab in Patients with Carboplatin-Taxane Based Chemotherapy in Advanced Ovarian Cancer–A Multicentre Randomised Phase III Trial

F. Heitz

Poster presentation, #TPS5612

A Phase II Study Evaluating the Efficacy of Niraparib and Dostarlimab (TSR-042) in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

V. Karivedu

Poster presentation, #TPS6105

A Randomized Phase Ib/II Study of Niraparib (Nira) plus Either Nivolumab (Nivo) or Ipilimumab (Ipi) in Patients (Pts) with Platinum-Sensitive Advanced Pancreatic Cancer (aPDAC)

K. Reiss

Poster discussion, #4021

Results of a Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and other DNA Damage Response Pathway Deficient Neoplasms

T. George

Poster presentation, #3122

Role of Cytoreductive Surgery for the Second Ovarian Cancer Relapse in Patients Previously Treated with Chemotherapy Alone at First Relapse: A Subanalysis of the DESKTOP III Trial

J. Sehouli

Poster discussion, #5520

Single Agent PD-1 Blockade as Curative-Intent Treatment in Mismatch Repair Deficient Locally Advanced Rectal Cancer

A. Cercek

Late-breaking oral presentation, #LBA5

Full list of GSK’s presentations at EHA (Free EHA Whitepaper):
Abstract Name

Presenter

Presentation Details

DREAMM-9: Phase I Study of Belantamab Mafodotin Plus Standard of Care in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma​

S. Usmani

Poster session, #P942​

Exploring Alternative Dosing Regimens of Single-Agent Belantamab Mafodotin on Safety and Efficacy in Patients with Relapsed or Refractory Multiple Myeloma: DREAMM-14​

M. Hultcrantz

Online publication, #PB2022​

Safety and Clinical Activity of Belantamab Mafodotin with Lenalidomide Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-6 Arm-A Interim Analysis

H. Quach

Poster session, #P941

Safety and Clinical Activity of Belantamab Mafodotin with Pembrolizumab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-4 Study​

A. Suvannasankha

Poster session, #P940​

Survival Outcomes of Patients with Multiple Myeloma in France: A Cohort Study Using the French National Healthcare Database (SNDS)​

X. Leleu

Poster session, #P943​

Synergistic Effects of Low Dose Belantamab Mafodotin in Combination with a Gamma-Secretase Inhibitor (Nirogacestat) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-5 Study​

A. Nooka

Poster session, #P939​

Full list of investigator-sponsored studies at EHA (Free EHA Whitepaper):
Abstract Name

Presenter

Presentation Details

A Phase I/II Single Arm Study of Belantamab Mafodotion, Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: AMARC 19-02 BelaCarD Study

M. Lasica

Poster session, #P946

Efficacy and Safety of Belantamab Mafodotin Monotherapy in Patients with Relapsed or Refractory Light Chain Amyloidosis: A Phase 2 Study by the European Myeloma Network

E. Kastritis

Poster presentation, #P914

Safety and Efficacy of Belantamab Mafodotin in Combination with RD in Newly Diagnosed, Transplant Ineligible Multiple Myeloma Patients: A Phase I/II Study by the Hellenic Society of Hematology

E. Terpos

Oral presentation, #S178

About multiple myeloma
Multiple myeloma is the second most common blood cancer in the US and is generally considered treatable, but not curable.[ii],[iii] In the US, more than 32,000 people are estimated to be diagnosed with multiple myeloma this year and nearly 13,000 people will die from the disease.[iv] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[v]

About ovarian cancer
Ovarian cancer is the 8th most common cancer in women worldwide.[vi] Despite high response rates to platinum-based chemotherapy in the front-line setting, approximately 85% of patients will experience disease recurrence.[vii] Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence.

About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. It is the most common gynaecologic cancer in the US and second most common gynaecologic cancer globally.[viii] Approximately 15-20% of women with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.[ix]

Important information for BLENREP in the EU
Indication
BLENREP is indicated as monotherapy for the treatment of multiple myeloma in adult patients, who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Refer to the BLENREP Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

About Dostarlimab
Dostarlimab 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.[x] In addition to GARNET, dostarlimab is being investigated in other registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumours or metastatic cancers.

Dostarlimab was discovered by AnaptysBio 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: dostarlimab (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 assets under the Agreement.

Important Information for JEMPERLI in the EU
Indication
JEMPERLI is indicated as monotherapy for the treatment of 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 Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies.

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.

Refer to the ZEJULA Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.