Übersicht des Medical Affairs Portal

The European Network for Gynaecological Oncological Trial groups (ENGOT) goal is to bring the best treatment to gynecological cancer patients through the best science, and enabling every patient in every European country to access a clinical trial

The mission of the International Myeloma Working Group (IMW) is to conduct collaborative basic, clinical, and translational research to improve outcomes for myeloma patients while providing scientifically validated, critically appraised consensus guidelines for the myeloma community globally.

The nternational Association for the Study of Lung Cancer (IASLC) is a global multidisciplinary organization dedicated to eradication of all forms of lung cancer.

The Society of Gynaecologic Oncology (SGO) made it it's mission to prevent and treat gynecologic cancers with equity, thereby improving lives through advocacy, engagement, education, research and collaboration.

The Society for Immunotherapy of Cancer (SITC) to improve cancer patient outcomes by advancing the science, development and application of cancer immunology and immunotherapy

The National Comprehensive Cancer Network (NCCN) Foundation Seeks to support the millions of patients and families affected by cancer by funding the NCCN Guidelines for Patients

The International Myeloma Society (IMS) is a professional, scientific, and medical society established to bring together clinical and experimental scientists involved in the study of myeloma

Die German Speaking Myeloma Multicenter Group (GMMG) ist eine akademisch ausgerichtete Studiengruppe aus Ärzten und Wissenschaftlern, die gemeinsam die Vision verfolgen, die Therapiemöglichkeiten für Myelompatienten zu optimieren, um ihre Prognose und Lebensqualität zu verbessern.

The European Society of Gynaecological Oncology (ESGO) is the leading European organisation with more than 2,500 professionals involved in treatment, care and research of gynaecologic cancers.

European Society for Medical Oncology (ESMO) is Europe's leading medical oncology society, providing a professional network for its members and working with national societies across Europe.

Die German Study Group für Myeloproliferative Neoplasien (GSG-MPN) vereint Experten, die sich intensiv mit der Erforschung von MPN-Erkrankungen und deren Behandlung beschäftigen.

The European School of Haematology (ESH) is a not-for-profit institution for continuing education founded in 1985 to promote and facilitate access to state-of-the-art and cutting-edge knowledge in haematology and related disciplines at the European level.

The European Myeloma Network (EMN) is Aanon-profit organisation created to increase understanding of multiple myeloma and to produce effective research projects and clinical trials.

The European LeukemiaNet Consortium (ELN) Foundation is a non-profit charitable organisation, which supports the goals of the European LeukemiaNet

The International Myeloma Foundation (IMF) is the first and largest global organization focusing specifically on multiple myeloma.

Die Nordostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO e.V.) ist eine internationale Vereinigung mit rund 900 Mitgliedern, die als Arzt oder Facharzt für gynäkologische Onkologie tätig sind.

Die Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) verfolgt die Förderung von Wissenschaft und Forschung sowie die Aus- und Weiterbildung von Ärzten in den Fachgebieten und Aufgaben der gynäkologischen Onkologie, einschließlich Brusttumoren.

Die Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGPB) ist spezialisiert auf die Verbesserung der Prävention, Diagnose und Therapie von Atemwegs- und Lungenerkrankungen.

Der Deutsche Krebskongress (DKK) ist der größte und älteste Kongress für Krebsdiagnostik und -therapie im deutschsprachigen Raum.

Die Deutsche Studiengruppe Multiples Myelom ist unter der Leitung von Prof. Dr. Hermann Einsele seit 2005 Mitglied im Kompetenznetz Maligne Lymphome.

Die Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e. V. Der DGHO e. V. ist ein Zusammenschluss von Ärzten, Wissenschaftlern und Interessierten, die sich auf die Erforschung, Diagnose und Behandlung von Blutkrankheiten und bösartigen soliden Tumoren spezialisiert haben.

Die Arbeitsgruppe für Innere Onkologie in der Deutschen Krebsgesellschaft (AIO) hat die wichtigsten Aufgaben bei der Durchführung klinischer Studien und bei der Sicherung und Optimierung der Qualität der medikamentösen Tumortherapie.

Das erklärte Ziel der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) e. V. e. V. soll Gynäkologie und Geburtshilfe weiterentwickeln und das evidenzbasierte Niveau der bundesweiten Versorgung kontinuierlich stärken.

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The European Multiple Myeloma Academy (EMMA) is a professional organization of doctors and other health care providers, who are interested in the latest developments in the management of patients with multiple myeloma.

Conclusions - In patients with advanced OC, 1L niraparib maintenance treatment was associated with a significant gain in QA-PFS compared with placebo, indicating a patient-relevant improvement in PFS. ● Niraparib increased restricted mean PFS without significantly increasing TOX time (duration of symptomatic grade ≥2 AEs prior to disease progression). The significant gain in TWiST demonstrates that niraparib-treated patients remained symptom-free for longer than those who received placebo. ● Collectively, the significant gains in QA-PFS and QA-TWiST demonstrate that niraparib maintenance treatment is associated with a PFS improvement whilst preserving patients’ HRQoL.

In 341 patients with dMMR solid tumors, dostarlimab demonstrated durable antitumor activity and consistent response rate across 16 tumor types with extended follow-up of 2 or more years – Objective response rate (ORR) was 44%, with the majority of patients having reduction in tumor volume – Median duration of response was not reached (range, 1.18+ to 47.21+ months) – 72.2% of responders had a response lasting ≥12 months The safety profile was acceptable with manageable toxicities, with only 7.3% of patients discontinuing treatment because of a treatment-related adverse event (TRAE

C High expression of programmed death ligand 1 (PD-L1–H) and high TMB (TMB-H) are more common in dMMR tumors; however, a subset of mismatch repair proficient (MMRp) tumors are PD-L1–H and/or TMB-H – Most dMMR tumors are also TMB-H (≈80%). Some MMRp tumors (6%) are also TMB-H – PD-L1–H occurs in ≈50% of dMMR tumors and in ≈40% of MMRp tumors ● In dMMR tumors there is considerable overlap of PD-L1–H and TMB-H; however, most PD-L1–H MMRp tumors are not TMB-H – Most TMB-H tumors are PD-L1–H, regardless of MMR status – In the MMRp patients, the sample size is not sufficient to determine if TMB alone, or TMB and PD-L1–H together, may predict response ● Differences in the distribution of TMB and CPS scores by cohort existed, and future research may refine the optimal cutoff points for each tumor type or an overall cutoff ● In summary, patients with high neoantigen production (TMB-H) and/or inflamed microenvironment (PD-L1–H) have increased objective response rate (ORR) compared to tumors with an absence of these features

No new safety signals were detected with dostarlimab compared to other anti–PD-1 inhibitors ● Most treatment-related adverse events (TRAEs) were low grade and occurred in the first 4 cycles (the first 12 weeks of treatment) — Some cases occurred later, suggesting a need for ongoing monitoring — The irTRAE hypothyroidism peaked during cycle 4 and occurred throughout the study period ● Few increases in the incidence of TRAEs were seen during cycle 5, following the transition to the 1000 mg every 6 weeks (Q6W) dosing schedule — The TRAEs with increased incidence after transition were fatigue and lipase increased ● Across the categories of grade ≥3 TRAEs observed, the majority resolved with a median time to resolution ranging from 1 to 30 days

These results showed that patients with advanced or recurrent EC received variable active treatment following PBCT – Overall, a large percentage of patients received no active therapy at index and, for those who did, the most common was doxorubicin monotherapy; this trend was similar across all countries • More than half (56% [151/271]) of patients did not respond to post-platinum treatment and, for those who progressed, treatment options were limited, suggesting that effective treatments are still needed – Patient response rates to CT reported here are higher than clinical trial rates. 6 This may be due to the majority of patients being ECOG 0/1 and/or physician selection bias of selecting responders • This study found that MSI or MMR testing is not common in clinical practice in the EU and varies between countries, highlighting the need to increase biomarker testing • As this was a chart abstraction, some limitations exist, including that data were originally collected for clinical practice and not research purposes, differences in data collection and reporting may exist between participating physicians and countries, and there may be patient selection bias by the physicians

• Improved OS was observed with dostarlimab compared with doxorubicin in pts with A/R EC • Dostarlimab and doxorubicin safety profiles were consistent with previous studies • There are inherent limitations with this type of comparison. IPTW is not a replacement for direct head-to-head comparison in a randomized controlled trial. Despite mASM, inter-study differences in assessment timing may impact results. A lower number of pts received dostarlimab compared with doxorubicin. There could also be an unknown impact of doxorubicin on MMR/MSI status • Overall, this ITC suggests a favorable benefit:risk profile for dostarlimab in pts with dMMR/MSI-H A/R EC

CONCLUSIONS In Chinese patients from the NORA study • Compared to fixed starting dose in NOVA, niraparib with ISD in NORA showed improved safety and comparable efficacy in the overall study population.1,3 • Platelet count decrease and neutrophil count decrease were the major haematologic TEAEs necessitating niraparib dose modification, the frequency of which decreased substantially three months after niraparib initiation. • Upon achieving stable, optimised doses in majority of patients, the PFS was comparable between subgroups receiving niraparib MT at 200-mg and 100-mg dose levels

ZEAL-1L (NCT04475939) is a Phase 3, randomised, double-blind trial in patients with advanced or metastatic NSCLC without known driver mutations that will compare efficacy and safety of nira + pembro with placebo + pembro

Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H and MMRp/MSS advanced or recurrent EC ▪ Median follow-up time is 27.6 (dMMR/MSI-H) and 33.0 (MMRp/MSS) months • Cohort A1 is the largest cohort of patients with dMMR/MSI-H EC studied with an anti–PD-1 monotherapy to date ▪ The probability of remaining in response at 24 months was 83.7% • Dostarlimab is the only PD-1 therapy clinically tested with a Q6W dosing schedule in endometrial cancer ▪ The safety profile was manageable ▪ The majority of TRAEs were grade 1 or 2 ▪ Discontinuation rates were low o 8.6% of patients discontinued treatment because of a TRAE

● Dostarlimab’s antitumor activity and safety for patients with dMMR/MSI-H EC and mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC were generally comparable across age groups – Objective response rates were similar across age groups for patients in both the dMMR/MSI-H EC and the MMRp/MSS EC cohorts – Incidences of grade ≥3 treatment-related adverse events (TRAEs) were low across all subgroups ● Older patients with advanced/recurrent dMMR/MSI-H EC experienced broadly similar treatment benefits as younger patients ● Dostarlimab can be used safely in older patients with advanced/recurrent dMMR/MSI-H EC

Combining the multimodal MoA of belamaf with other anticancer agents with complementary MoA may have additive or synergistic effects, increasing efficacy or duration of response. Single-agent belamaf (2.5 mg/kg Q3W) achieved deep and durable responses (ORR=32%; ≥VGPR in 58% of responders; mDOR=11 months; mOS=13.7) with a manageable safety profile in triple-class refractory patients with RRMM in the phase 2 DREAMM-2 trial (NCT03525678) The preliminary ORR for the total DREAMM-5 belamaf + aICOS DE study population (N=25) was 52% (n=13; 95% CI: 31.3–72.2), with 57% of responders (8/14) achieving ≥VGPR. In this combination study, 21 patients (84%) of the total DE population experienced an AE related to study treatment and 13 patients (52%) experienced Grade 3 or 4 AEs due to study treatment; AEs were managed with dose reductions and delays. Conclusion: In this interim analysis, belamaf combined with aICOS showed encouraging clinical activity along with a safety profile that was manageable through dose modifications in triple-class refractory patients with RRMM

Modulares, CME-zertifiziertes Webinar zum Endometriumkarzinom "State of the Art von der Diagnose bis zur zielgerichteten Therapie"

The American Society of Hematology (ASH) is a professional organization representing hematologists

The European Hematology Association (EHA) is a non-governmental and not-for-profit membership organization that is guided by its mission to promote excellence in patient care, research, and education in hematology.

Conclusions - This real-world analysis shows that adoption of PARPi monotherapy in the 1L maintenance setting in patients with newly diagnosed advanced ovarian cancer has increased between 2017 and 2021 - PARPi use, when compared with active surveillance, was associated with significantly improved median progression-free survival (PFS) and was an independent predictor of improved PFS in patients with BRCAm or BRCA wild-type (BRCAwt) as well as patients with HRd or homologous recombination proficient (HRp)/homologous recombination deficiency (HRD) unknown statu

Conclusions The ORR observed with niraparib in combination with dostarlimab did not reach the threshold for second stage accrual, highlighting that PROC is difficult to treat and there remains an unmet need for effective treatments for patients with PROC and no known BRCAm, and prior bevacizumab treatment. Although DCR was 29.3%, futility was declared based on low ORR. PD-L1 status did not predict response, highlighting the need for robust biomarkers to predict response in PROC. The safety of the combination was simil

Conclusions OVARIO enrolled a high-risk population • 63% received NACT/IDS; 42% had PR following 1L platinum-based therapy in combination with bevacizumab • In the overall population, more than half (53%) of patients remained progression free at 24 months • 63% remained progression free in the HRd subgroup, and 42% in the HRp subgroup • Median TFST was 17.5 months, and median TSST was not reached in the overall population • PFS analysis suggests that the combination of niraparib and bevacizumab maintenance is efficacious; clinical benefit was observed in the overall population, and across biomarker subgroups in a continuum • Overall: mPFS of 19.6 months (95% CI 16.5–25.1) • HRd subgroup: mPFS of 28.3 months (95% CI 19.9–NE) and not yet reached in the BRCAm subgroup • HRp subgroup: mPFS of 14.2 months (95% CI 8.6–16.8) • There was no clinically meaningful impact on QoL as assessed by change in FOSI score • Safety of niraparib in combination with bevacizumab was consistent with the known side effects of each treatment as monotherapy, and no new safety signals were observed • Rate of treatment discontinuation is higher for combination therapy than for monotherapy alone, consistent with other PARPi + bevacizumab studies

Studies exploring alternative dosing regimens and combination strategies have shown promising preliminary results,7,8 and retrospective analyses of DREAMM-2 data show a correlation between BCVA changes, patient-reported outcomes, and keratopathy9 that suggests ocular symptoms and severity of visual acuity changes may be a surrogate for keratopathy severity. These findings highlight that alternative dosing approaches or monitoring may be useful to reduce rates or severity of corneal events without compromising efficacy

GSK is exploring different clinical assets aimed at augmenting the immune response, reducing immune suppression, and modulating the tumor microenvironment

The OSDI is a brief patient reported outcome questionnaire that assesses eye symptoms and vision related functioning, requiring 2–3 minutes to complete. • It is feasible to use the OSDI in a range of patients, with options for self-completion and interview administration, including those with grade 3–4 keratopathy. • Based on these analyses, the majority of Grade 3–4 keratopathy are associated with a worsening of OSDI symptoms or functioning. • The results from this hypothesis-generating post-hoc analysis suggest that in addition to visual acuity and symptoms, hematologists/oncologists may be able to use patient reported outcomes such as the OSDI as potential clinical surrogate marker for corneal exam results. • This approach provides some insight into the relationship between corneal exam findings and ocular symptoms and will be explored further in trials with other belamaf dose regimens. If the results are validated, ocular symptoms, changes in OSDI, visual acuity declines, may help guide dosing. • It may be possible for hematologists/oncologists to manage belamaf dose modifications, due to ocular AEs, without a confirmatory eye exam by the ECP, therefore potentially reducing the burden to the patient

This study highlights wide variations in treatment regimens after triple exposure to an immunomodulatory agent, a PI, and daratumumab. Triplet regimens were predominant after the triple-class exposure. Retreatment with the same agents was common during the follow-up period, with three quarters of patients receiving PIs or immunomodulatory agents, and half of patients receiving daratumumab. Despite the high retreatment rate, the estimated survival following the triple exposure was low, demonstrating the need for novel treatments that may improve outcomes in patients with RRM

Patients with MM experience worsening survival outcomes with increasing time from diagnosis and with subsequent line of therapies (LOT). • Median OS was better among TCE patients with subsequent treatment (9.4 mos) or patients with TCE with LOT5+ (8.2 mos) but worse in TCE patients without subsequent treatment (0.9 mos) and TCE patients with LOT4 without subsequent treatment (1.0 mos) • Increased age, presence of comorbidities, and nonSCT status, shorter time between LOTs, and earlier onset of TCE status were associated with worse survival outcomes and may be associated with more aggressive disease. • Overall, this study provides evidence of unmet needs in the management of patients with MM in France, which may be addressed by updating realworld practice with regimens shown to improve patients’ overall survival in clinical trials. • Despite therapeutic advances an unmet need for improved access to novel therapies with unique mechanisms of action remains, especially in those TCE patients

This preliminary data suggests a manageable safety profile with low-dose belamaf (0.95 mg/kg Q3W) + nirogacestat (100 mg BID continuously) combination in patients with heavily pretreated RRMM. • Reduced ocular events, particularly Grade ≥3, 12.5% (2/10 in DE and 1/14 in CE) were observed in patients dosed with low dose belamaf + nirogacestat. • The ORR in belamaf + nirogacestat combination cohorts was 38% (9/24) and 17% achieved VGPR (4/24). • New sub-studies will evaluate belamaf + nirogacestat with standard of care treatments (Rd, Pd) as a quadruplet regimen to improve efficacy and reduce ocular events in patients with RRMM.1

Based on contemporary RW clinical practice data, this analysis of the Adelphi Real World MM III DSP™ survey of hematologists and hemato-oncologists in the USA showed, across all LOTs: • High variability in treatment approach for patients with MM. • A trend for use of triplet therapies. • High retreatment rate with the same drug class. Physicians rated survival data and clinical efficacy as the key factors influencing their patient treatment choices. These RW findings highlight high rates of relapse and the unmet need for new treatment strategies in patients with RRMM

Heavily pre-treated RRMM patients have limited treatment options as evidenced by: • High rates of retreatment with PIs, immunomodulatory agents, and daratumumab, even after becoming refractory to these agents • Reliance on investigational agents for patients with refractory disease. • TCR patients with MM had suboptimal and shorter median OS, DOT, and TTNT when compared to DCR and double-exposed cohorts. • Higher baseline LDH levels, higher ECOG performance scores, and high-risk cytogenetic abnormalities were associated with increased risk of death, shorter DOT, and shorter TTNT. • The inferior outcomes and reliance on retreatment with agents after becoming refractory highlight the high level of unmet need for new treatments for these RRMM patients. Author email address: feng.9.wang@gsk.com Treatment discontinuations • Reasons for treatment discontinuations in the double-exposed, DCR, and TCR groups are shown in Table 2.

Dostarlimab has an acceptable safety profile with manageable adverse events when analysed over the dMMR and mismatch repair proficient (MMRp) EC safety population of the GARNET trial ● Only 5.5% of patients discontinued treatment because of treatment related adverse events (TRAEs) ● TRAEs and immune-related TRAEs (irTRAEs) were seen in a low percentage of patients ● TRAEs and irTRAEs were seen more frequently earlier in the time course of dostarlimab treatment – irTRAEs were infrequent but could be seen throughout the course of treatment, so careful monitoring is necessary ● No increase in the rate of TRAEs or irTRAEs was seen when changing to the 1000-mg Q6W dosage of dostarlima

Safety with dostarlimab was consistent with the anti– PD-1 drug class ● Safety was consistent across tumor types ● Most treatment-related adverse events (TRAEs) were low grade, with few leading to interruption or discontinuation ● No overall increase in the rate of TRAEs was seen after transitioning to the 1000-mg Q6W dosing schedul

TMB-high (TMB-H) status and dMMR/MSI-H status show substantial overlap in the patient populations with EC ● TMB-H and dMMR/MSI-H EC have similar response rates ● Notably, the objective response rate (ORR) of patients with mismatch repair proficient (MMRp) and TMB-H EC was comparable to the ORR of patients with dMMR/MSI-H and TMB-H EC – TMB-H status in the patients with MMRp EC was not due to MSI-H (hypermutated) or POLε-mutated (ultramutated) status ● The study was not powered to assess antitumor activity by TMB status, and interpretation is limited by the small number of patients in each subgrou

Safety with dostarlimab was consistent with the anti– PD-1 drug class ● Safety was consistent across tumor types ● Most treatment-related adverse events (TRAEs) were low grade, with few leading to interruption or discontinuation ● No overall increase in the rate of TRAEs was seen after transitioning to the 1000-mg Q6W dosing schedul

American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer.

Modulares Webinar zum Ovarialkarzinom "State of the Art - von der Diagnose bis zur Rezidivtherapie" (4 CME Punkte). Zertifiziert bis 09/2023.

Preliminary data suggest the combination of belamaf and VRd in patients with TI NDMM resulted in a safety profile consistent with the known profile of belamaf in patients with RRMM. 3,4 • Lower rates of Grade ≥3 ocular events (KVA scale) were observed in the cohorts with extended dose schedules and lower doses, while maintaining high ORR. Belamaf + VRd demonstrated high response rates in patients with TI NDMM, with deep responses of ≥VGPR achieved in more than half of all patients in each cohort (67–92%). • All 10 patients with ≥VGPR who were tested for MRD negativity in Cohort 1 were MRD-negative. Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baseline patient characteristics. Additional patients will be recruited for Cohorts 6–8, and further follow-up is anticipated for Cohorts 1–5, to confirm safety and efficacy of belamaf + VRd in patients with TI NDMM. 10

Belamaf + Len/Dex demonstrated a tolerable safety profile, with no new safety signals identified. Encouraging clinical activity, albeit in small sample sizes, is observed with this combination in patients with RRMM. • Belamaf + Len/Dex demonstrated clinical activity, with the highest ORR reported in the 1.9 mg/kg Q4W and 2.5 mg/kg Q4W (split) cohorts (75% and 69%, respectively). • In addition, the 2.5 mg/kg Q4W cohort reported an ORR of 63% (10 out of 16). Of those with an ORR, 80% (8 out of 10) demonstrated a deeper response (≥VGPR). • mDOR was not reached in any of the cohorts except the 1.9 mg/kg Q4W cohort (11.1 months). • mPFS was reached in the 1.9 mg/kg Q4W and 2.5 mg/kg Q4W (split) cohorts. Belamaf PK profile was similar to that observed in patients with RRMM, taking into consideration baseline patient characteristics, and there was no PK interaction between lenalidomide and belamaf. Belamaf has been found to induce deep and durable responses over time, as demonstrated in the DREAMM-2 study. 6,7 Therefore, it is hypothesized that ORR in this study will increase across all cohorts with prolonged exposure. Further studies are ongoing to better understand the clinical benefit and safety of combining belamaf with Len/Dex in patients with RRMM.

Belamaf + pembro demonstrated clinical activity and an appreciable ORR compared with the ORR of 32% reported in the DREAMM-2 study of belamaf monotherapy in patients with heavily pre-treated RRMM. 7 • The ORR of 43% (95% CI: 24.5–62.8) in Part 2 was not statistically significant, and therefore the null hypothesis of ORR ≤40% was not rejected. No new treatment-related AEs were identified; AE frequency and severity were similar to belamaf monotherapy. There was no apparent effect of concomitant pembro administration on total monoclonal antibody and cys-mcMMAF pharmacokinetics, nor on the pattern of sBCMA levels over time, compared to belamaf monotherapy. The results of this study help reinforce the body of research supporting belamaf use in patients with MM, and future studies will pursue other combination therapy options to enhance the efficacy-safety profile