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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 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

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

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.

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 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

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.

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

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.

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.

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

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

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

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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.

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

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

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

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

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

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.

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

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

● 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

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

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

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

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.

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

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

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

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 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

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

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

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

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

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 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.

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

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.

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.

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

These data represent the most extensive BMF assessment in patients with MF to date (>300 paired biopsies and mature clinical data across distinct JAKi in treatment-naïve patients) Approximately 20% of JAKi-naïve patients experienced ≥1 grade BMF improvement within 24 weeks of either momelotinib or ruxolitinib treatment However, BMF changes from baseline to week 24 did not correlate with week 24 symptom or spleen response, anemia improvement, or long-term OS Given the lack of association with OS, these findings indicate the need to better understand BMF changes by week 24 as a surrogate for clinical benefit and disease modification

In this updated analysis, OL momelotinib maintained week 24 symptom, TI, and spleen responses with continued favorable survival and safety Momelotinib is the first and only JAK1 and JAK2 inhibitor that also decreases hepcidin through ACVR1 inhibition, thus providing benefit for patients with MF and anemia, which is an unmet need in MF treatment These findings support the potential use of momelotinib as an effective treatment in patients with MF, particularly in patients with anemia and thrombocytopenia

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.

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

In the phase 3 MOMENTUM study, all prespecified primary and key secondary endpoints were met − Significant improvements in symptoms, spleen size, and anemia measures were observed with momelotinib vs danazol − Momelotinib was associated with a favorable safety profile and trend towards improved overall survival Momelotinib is the first and only JAK1 and JAK2 inhibitor that also decreases hepcidin through ACVR1 inhibition − This may contribute to rapid and sustained improvements in hemoglobin levels and transfusion requirements Momelotinib exhibits a consistent profile across thrombocytopenic subgroups, as described on a separate poster at this meeting Momelotinib exhibits a consistent profile across thrombocytopenic subgroups, as described on Poster 117 These findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia

Patients receiving momelotinib in the MOMENTUM study demonstrated greater and consistent improvement in symptoms compared with danazol, using responder analysis, longitudinalresponder analysis, and time to event analyses Momelotinib showed significantly greater symptom and quality oflife improvement compared with danazol at week 24 for fatigue,abdominal discomfort, night sweats, pain, physical function, socialfunctioning, role functioning, insomnia, and global HRQOL asmeasured by MFSAF, EORTC QLQ-C30, and PROMIS questionnaires Consistent with the primary end point of MOMENTUM, the higher magnitude of response and faster response demonstrate that momelotinib provides progressive and durable symptom benefit (also shown in MOMENTUM week 48 oral presentation 627

In thrombocytopenic, symptomatic, and anemic patients with MF, including those with platelet counts as low as 25×10^9/L, momelotinib was administered safely and demonstrated improvements in symptom responses, transfusion independence rates, and spleen responses as compared with danazol Consistent with the overall intent-to-treat MOMENTUM population, platelet counts remained stable over time, and a trend toward improved overall survival versus danazol was maintained, in thrombocytopenic MF patients treated with momelotinib Momelotinib, which is the first and only JAK1 and JAK2 inhibitor that decreases hepcidin through ACVR1 inhibition, may address a critical unmet need particularly in symptomatic MF patients with anemia and thrombocytopenia

In MOMENTUM, in symptomatic and anemic patients with myelofibrosis, momelotinib showed significant benefit with higher TI response rates and lower transfusion burden compared with DAN In patients achieving week 24 TI-R, OS was significantly improved compared with patients who were non-TI Both MOMENTUM and the SIMPLIFY studies suggest that achieving week 24 TI-R on momelotinib may be a potential surrogate for improved OS TD patients not achieving TI on-study were still more likely to have reduced transfusion burden (become TR) on momelotinib when compared with DAN TD patients becoming TR by week 24 also demonstrated a significant improvement in OS Given the association of improved OS with reduced transfusion burden, this provides a potential signal of disease modification

TD in patients with myelofibrosis led to significantly higher rates of health care resource utilization and costs compared with non-TD patients, even after controlling for differences in age, gender, and baseline comorbidity The higher economic and clinical burden of TD is driven only in part by the higher number of transfusions Only a small proportion of patients with myelofibrosis diagnoses across all risk and disease durations within the IBM MarketScan Commercial Claims and Encounters Database are transfusion dependent. These results warrant the ongoing investigation in older populations This study highlights the need for additional therapeutic options to limit progression to TD and offset costs for patients with myelofibrosis

This study reports the largest clinical trial safety database to date in patients with JAKi-naive or -experienced myelofibrosis Most patients tolerated continuous treatment with momelotinib without cumulative toxicity Consistent with the lack of increasing hematologic AEs over time, hemoglobin and platelet values improved or remained consistent, respectively Peripheral neuropathy was mostly mild/moderate and noncumulative The risk of second primary malignancies and AML were not increased for a myelofibrosis population This integrated analysis demonstrated the long-term safety of momelotinib in patients with myelofibrosis from early to late stages, and with varying degrees of anemia

Momelotinib has undergone unique and extensive analysis in patients who transitioned from RUX without tapering or washout of RUX Transitioning to momelotinib from RUX can rapidly improve anemia and shift patients to TI without compromising splenic control Momelotinib requires once-daily dosing, infrequent dose modifications, and is very well tolerated during the transition after RUX and beyond No symptoms associated with withdrawal were observed when patients transitioned from RUX, which is often a clinical issue when transitioning between JAKis Administering momelotinib immediately after RUX, without tapering or washout, is safe, maintains symptom benefit and spleen volume, and improves anemia in patients with myelofibrosis

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 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

• In this analysis of 1778 patients who received ≥ 2 LOTs for RRMM treatment, most patients were retreated with an IMiD or a PI in 2L and 3L therapy • Although sample sizes were limited, some trends in the time-to-event outcomes may exist, suggesting some retreatment options may be suboptimal in a real-world setting • The variation in retreatment patterns between countries was more prominent with LEN-based regimens compared with others • When choosing to retreat with BORT or LEN, most physicians cited “following treatment guidelines” as a common reason; but health insurance coverage appeared to have influenced retreatments with DARA • Disease progression was cited as the primary reason for stopping a retreatment regimen, regardless of agent and/or LOT • These real-world data on retreatment patterns implies there is a need for novel treatments for RRMM with new mechanisms of action

• Belamaf + Len/Dex demonstrated a tolerable safety profile, with no new safety signals identified. • 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. • 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.

• Baseline ocular conditions were very common in the DREAMM-2 patient population, with 90% of patients having at least one baseline ocular condition • Some ocular symptoms were more common in patients with cornea-related baseline ocular conditions, such as keratopathy and dry eye • Patients with baseline age-related macular degeneration experienced an increased number of symptoms; however, this may be confounded by the small number of patients • There was little evidence that baseline ocular conditions not related to the cornea, such as cataracts, glaucoma, or blepharitis, had any effect on treatment-emergent ocular symptoms • These findings inform risk/benefit decision-making with belamaf and indicate that belamaf can be a treatment option for patients with RRMM despite the presence of baseline ocular conditions

• The results of adding belamaf to VRD seem encouraging, although ocular toxicity is a concern. • The study is with belamaf as part of the maintenance. • Longer follow-up will confirm whether the combination improves outcomes in NDTE MM patients.

• In France, Germany, Italy, Spain, and the UK, there were large variances in MM treatment regimens used by LOT, especially in 3L and beyond. • Triplet treatment regimens were the most common, regardless of LOT; however, in the UK, the use of triplets was lower in 2L and beyond • Belamaf use in 4L in Spain, Italy, and France may reflect treatment in the early access program or real-world utilisation patterns • Efficacy and safety were the main reasons for prescribing treatment, and disease progression was the main reason to stop treatment • Lack of standard care after 2L demonstrates an unmet need exists in these patient

• The results of the ALFA study were consistent with the DREAMM-2 trialin an overall older and more frail population. • In the ALFA overall population, the ORR was 32.7%, CBR was 36.4%, mPFS was 2.4 months, and mOS was 8.8 months. In patients ≥VGPR to BLMF, mPFS was 20.6 months and mOS was not reached. • No new safety concerns were identified. These data, presented from the largest real-life study conducted to our knowledge, confirm previous results

• These findings provide important insights into the real-world use of belamaf in patients with RRMM. Patients in this study were heavily pre treated with multiple comorbidities and belamaf can help fill the unmet treatment need. • Overall, patients with RRMM treated with belamaf in the clinical real-world setting experienced similar outcomes to those who received belamaf in the DREAMM-2 study, including therapy holds to address ocular AESI. Ocular events were managed by HCPs, and patients were remaining on treatment.

• This study provides insights on patients’ valuation of RRMM treatment attributes when provided with data outside of a clinical consultation and highlights the need for a shared decision-making process for optimal treatment selection

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• 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.

• 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. • 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

• 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 keratopathy and ocular symptoms without compromising efficacy

• Preliminary data suggest the combination of belamaf and VRd resulted in a safety profile consistent with the known profile of belamaf in patients with RRMM. • Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baselinepatient characteristics. • The study is ongoing to confirm safety and the efficacy of belamaf + VRd for in TI NDMM patients.

•Among patients with MF who required RBC transfusions at baseline, treatment with momelotinib demonstrated an ability to deliver higher SVR, transfusion independence, and TSS response rates compared with BAT/RUX •With momelotinib, 25 patients in this baseline non-TI subgroup (35%) became TI (terminal 12-week criteria) at week 24 vs only 1 patient (3%) with BAT/RUX •Durability of transfusion independence with momelotinib is suggested by the similar TI response rates per terminal and rolling 12-week criteria (35% and 40%, respectively) •Mean Hb levels in this subgroup improved rapidly with momelotinib and remained higher than in those treated with BAT/RUX through week 24, despite the momelotinib arm having a lower median transfusion rate than the BAT/RUX arm during that period •Safety results in this subgroup were consistent with those previously reported for the ITT population •Collectively, these data suggest that in patients who need RBC transfusions, outcomes—notably anemiabenefits, including week 24 transfusion independence rate, median transfusion rate through week 24, and mean Hb levels over time—are improved by switching to momelotinib rather than continuing RUX and using ESAs or other supportive therapies to manage anemia

•Across 3 phase 3 trials, patients treated with momelotinib spent less time reliant on RBC transfusions and more time free from transfusions and anemia events compared with those treated with ruxolitinib, BAT, or danazol •The largest differences were observed with momelotinib vs ruxolitinib (SIMPLIFY-1) or BAT (88.5% ruxolitinib; SIMPLIFY-2) •However, momelotinib was also associated with less time reliant on RBC transfusions than danazol, a guideline-recommended supportive therapy for anemia managment in MF, in MOMENTUM •Incorporating anemia events into the TWiTR-An analyses had minimal impact on health state durations vs the TWiTR analyses. particularly in the JAK inhibitor-experienced setting (SIMPLIFY-2, MOMENTUM). consistent with the fact that more patients were TD at baseline in those trials •Given the negative QOL and prognostic impact of RBC transfusion dependence and achievement of transfusion independence with momelotinib may lead to improved quality of survival for patients with MF

•These data demonstrate that when accounting for differences in known prognostic factors and effect modifiers as well as changes in RBC transfusion status over time, a consistent and statistically significant relationship was observed between transfusion independence and OS across all 3 phase 3 momelotinibtrials •Consistent with inclusion of transfusion status in DIPSS-plus risk assessment,11these data support maintenance or achievement of TI status as a clinically relevant and meaningful endpoint that is prognostic for survival in JAK inhibitor–naive and –experienced disease settings, irrespective of other covariates •While factors such as sample size and follow-up that vary across trials impact the observed probability estimates for survival, the differing magnitudes of the separation between the TI and non-TI populations in each trial suggest that earlier initiation of momelotinib(eg, the JAK inhibitor–naive setting of SIMPLIFY-1) to maintain TI status or achieve it earlier may lead to more pronounced effects on OS •A limitation of these analyses is that evaluation of any potential differential impacts of these covariates on OS between momelotiniband comparator arms was not possible due to the crossover design of all 3 trials; all patients who remained in the trial after week 24 received momelotinib, confounding assessment of survival by treatment arm •Sensitivity analyses incorporating other time-dependent variables (eg, ferritin levels, platelet counts) and subgroup analyses (eg, baseline transfusion status) are being explored and may identify additional longitudinal changes that, along with transfusion status, impact OS in patients with MF

•Momelotinib was associated with improvements in RBC transfusion intensity and zero RBC transfusion status vs ruxolitinib in JAK inhibitor–naive patients with MF (SIMPLIFY-1) •Momelotinib treatment was associated with a reduction in mean RBC transfusion burden, while ruxolitinib was associated with increased mean RBC transfusion burden •Most patients who crossed over from ruxolitinib to momelotinib during the open-label phase experienced improved or maintained RBC transfusion burden vs baseline •These data suggest that increases in transfusion burden were delayed or prevented in patients treated with momelotinib compared with those treated with ruxolitinib •In JAK inhibitor–experienced patients with MF (MOMENTUM), momelotinib showed greater reduction in RBC transfusion burden from baseline vs danazol, which is a standard anemia therapy •Across both trials, ≥85% of patients treated with momelotinib either maintained or experienced improved transfusion intensity compared with baseline, highlighting that momelotinib provides consistent anemia benefit for the majority of patients

•Reductions in the need for transfusions associated with momelotinib are projected to result in meaningful healthcare system and patient savings in medical and transfusion-related costs relative to RUX in JAK-inhibitor-naive patients with MF. These findings were sonsistent in patients aged => 65years and patients with TD or TI/TR status at baseline •Patients with anemia (Hb <10g/dlL at baseline) had higher projected medical and transfusion-related cost savings with momelotinib compared with RUX •Momelotinib is also projected to provide time savings for patients on transfusion-related travel, procedure and recovery, and preparation and waiting compared with RUX •Future studies of real-world data are warranted to further ecaluate the impact of momelotinib on the clincial and economic, and humanistic burden in patients with MF

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•In the phase 3 SIMPLIFY-1 trial, spleen and symptom benefits with momelotinib vs ruxolitinib were generally consistent in patients with anemia (baseline Hb levels <10 or <12 g/dL) compared with the ITT population • TI rates at week 24 in patients with anemia were nearly doubled with momelotinib vs ruxolitinib (eg, >1.7-times higher in the <10 g/dL subgroup, at 47% vs 27%), including higher rates of both maintenance of TI and achievement of new TI •No new momelotinib safety signals were identified in patients with anemia, and rates of grade ≥3 hematologic treatment-emergent adverse events during the double-blind period were lower than those observed with ruxolitinib • Overall, these descriptive analyses highlight the favorable benefit-risk profile of momelotinib in JAK inhibitor–naive patients with myelofibrosis and anemia, thus representing a potential treatment option for this population

• Lower HRQOL and functioning at baseline were reported in patients with MF in the phase 3 SIMPLIFY trials of momelotinib compared with the general population, highlighting the detrimental impact of MF on PROs regardless of transfusion status • Lower mean scores across all SF-36v2 domains were reported in patients who were TD than in those who were TI, either at baseline or at week 24 in the SIMPLIFY trials, suggesting that transfusion dependence in MF has a further negative impact on multiple aspects of patient quality of life • Associations between baseline transfusion status and PROs were observed in the physical functioning, role-physical, and general health SF-36v2 domains in SIMPLIFY-1 • These results were supported by associations between transfusion status and the physical functioning and fatigue domains of the EORTC QLQ-30 in MOMENTUM • Greater improvement across the SF-36/2 physical functioning, role-physical, general health, social functioning, and mental health domains was reported in patients who were TD at baseline in the SIMPLIFY trials but became TI at week 24 compared with those who remained TD, supporting the importance of transfusion independent status for physical functioning. general health, mental health, and overall quality of life • Mean changes for patients who became Tl exceeded the MID for groups with low baseline scores in all domains except role-physical (MID, 3.0; mean change, 2.212 • Hb levels at both baseline and week 24 in the SIMPLIFY trials may be incrementally associated with SF-36v2 physical functioning score, although the association was modest • These analyses highlight the detrimental impact of transfusion dependence on several HRQOL domains, most notably those related to physical functioning and fatigue, and the benefits of achieving transfusion independence at week 24, supporting further research into the effects of transfusions and anemia on quality of life in MF

• In a phase 2 study of 41 RBC TD patients treated with momelotinib, 85% (35/41) achieved a numeric reduction in RBC transfusion requirements on treatment compared with baseline • Using ordinal bins to group patients based on baseline-period and treatment-period intensity of RBC units transfused per 28 days, 90% (37/41) experienced a decline or stabilization of transfusion requirements on treatment; no patients were RBC transfusion-free at baseline, but 9 (22%) had no RBC transfusions over the entire treatment period • Mean change in transfusion intensity from baseline was −1.5 RBC units per 28 days, a decrease from baseline of ≈50% • Overall, these novel transfusion burden analyses demonstrate that binary transfusion independence response/nonresponse (34% transfusion independence responders in this study) may not fully capture the anemia benefits of momelotinib, which was associated with reduced RBC transfusion burden in the majority ofpatients (85%) • The RBC TD population and frequent assessments in this phase 2 study were advantageous to the present analysis, but limitations include the small sample size and lack of a comparator arm • With this phase 2 study providing proof of concept for the novel RBC transfusion burden analyses described here, similar analyses in the larger, randomized controlled phase 3 studies of momelotinib are ongoing

• Momelotinib showed a favorable safety profile vs fedratinib in both JAK inhibitor—experienced and —naive patients during a 24-week treatment window from phase 2 or3 trials involving momelotinib and fedratinib • There wasa significantly lower risk of key hematologic AEs, including anygrade and grade 3/4 anemia in both patient populations • The risk of key gastrointestinal AEs such as nausea and diarrhea was significantly reduced with momelotinib vs fedratinib • The favorable safety profile is consistent with what has been observed vs ruxolitinib in SIMPLIFY-1 and SIMPLIFY-2, particularly with respect to rates of anemia • These data support the use of momelotinib as a safe and tolerable treatment option for JAK and JAK inhibitor—naive patients with MF

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