On June 11, 2022 EORTC reported that Acute myeloid leukemia (AML) predominantly occurs in older adults over 65 years, who exhibit a lower tolerance to conventional induction chemotherapy (IC) compared with younger patients (Press release, EORTC, JUN 11, 2022, View Source [SID1234615902]). Despite treatment with IC, older patients with AML have poor long-term survival without hematopoietic stem cell transplantation (HSCT). For the past decade, DNA-hypomethylating agents such as decitabine have been considered a safer alternative for patients who are unfit for IC. Prolonged (10-day) decitabine treatment has shown promising efficacy in previous studies with older patients with AML, and may be a more suitable treatment before HSCT than IC in fit patients.

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The open-label randomized phase III study of the EORTC Leukemia group, GIMEMA, CELG, and GMDSSG (NCT02172872) compared the efficacy and safety of 10-day decitabine with conventional 3+7 IC as a treatment before HSCT in older (≥60 years) patients with newly diagnosed AML. Patients with at least stable disease and an HLA-matched donor were encouraged to undergo HSCT after ≥1 treatment cycle.

The rate of HSCT in decitabine-treated patients was similar to IC-treated patients (40% vs 39%). Although IC achieved higher complete remission rates compared with decitabine (61% vs 48%), the overall survival was comparable, with a median overall survival of 15 months in the decitabine group and 18 months in the IC group. At 4 years, 26% of patients from the decitabine arm and 30% of patients
from the IC arm were alive. A notable difference between the treatment arms was the incidence of grade 3–5 adverse events before HSCT. Decitabine treatment showed lower incidences of febrile neutropenia, platelet reduction, oral mucositis, and diarrhea. In addition, the 30-day mortality rate was 3.6% for decitabine compared with 6.4% for IC.

In conclusion, decitabine treatment for older patients with AML exhibited a superior safety profile compared with IC while maintaining similar overall survival and rates of HSCT. The results of this study will be presented by Prof. Michael Lübbert on Saturday, June 11.

Presenter: Prof Dr med Michael Lübbert
Affiliation: Universitätsklinikum Freiburg, Freiburg, Germany
Presentation: S125 will be presented by Prof Michael Lübbert | Saturday, June 11, 2022 | 16:30 –17:45 CEST | Hall A7, Messe Wien Exhibition & Congress Center, Vienna, Austria.

About the EHA (Free EHA Whitepaper) Annual Congress

Every June, EHA (Free EHA Whitepaper) organizes its Annual Congress in a major European city. In 2020 and 2021, the format was virtual due to COVID-19. However, this year, EHA (Free EHA Whitepaper) has organized a Hybrid congress for the first time. The Congress is aimed at health professionals working in or interested in the field of hematology. The scientific program topics range from stem cell physiology and development to leukemia, lymphoma, diagnosis and treatment, red blood cells, white blood cells and platelet disorders, hemophilia and myeloma, thrombosis and bleeding disorders, as well as transfusion and stem cell transplantation.

On June 11, 2022 AbbVie (NYSE: ABBV) reported primary results from the large B-cell lymphoma (LBCL) expansion cohort in the EPCORE NHL-1 phase 2 clinical trial evaluating epcoritamab (DuoBody-CD3xCD20), an investigational subcutaneous bispecific antibody (Press release, AbbVie, JUN 11, 2022, View Source [SID1234615901]). In this study, epcoritamab demonstrated efficacy with durable responses in patients who had previously received at least two prior lines of anti-lymphoma therapy including chimeric antigen receptor (CAR) T-cell therapy. These data were presented today in a late-breaking oral presentation as a part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA2022) in Vienna, Austria (Abstract #LB2364).

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"Large B-cell lymphoma is a fast-growing, difficult to treat type of aggressive non-Hodgkin’s lymphoma. Some treatment approaches like chemotherapy and immunotherapy have been in place for decades and newer treatments like CAR T-cell therapies involve multiple steps before a patient can begin treatment so there is still a need for additional treatment options," said Professor Catherine Thieblemont, head of the Hemato-Oncology Department at Hôpital Saint-Louis, Paris, France. "The data presented today suggest that epcoritamab has the potential to provide patients living with LBCL an accessible, effective treatment with a safety profile that may fulfill an unmet need."

The study cohort, which included 157 relapsed/refractory LBCL patients, previously treated with a median of three lines of prior therapy, demonstrated an overall response rate (ORR) of 63 percent and a complete response (CR) rate of 39 percent. Baseline characteristics included 61 percent of patients who were refractory to primary treatment, 20 percent who had prior autologous stem cell transplantation (ASCT), and 39 percent who were treated with CAR T-cell therapy (75 percent of those refractory to CAR T). Patients enrolled in the study who were naïve to CAR T-cell therapy achieved a 69 percent ORR and a 42 percent CR and patients who received prior CAR T-cell therapy achieved a 54 percent ORR and a 34 percent CR. After a median follow up of 10.7 months, the median duration of response (mDOR) was estimated to be 12 months, while the mDOR among patients achieving a CR was not reached, with 89 percent still in CR at nine months. Topline results from this study were previously announced in April 2022.

The safety profile of epcoritamab was consistent with previous findings. The majority of treatment-emergent AEs (TEAEs) occurred during the first 12 weeks of treatment and resolved. The most common TEAEs of any grade (greater than or equal to 15 percent) included cytokine release syndrome (CRS) (49.7 percent), pyrexia (23.6 percent), fatigue (22.9 percent), neutropenia (21.7 percent), diarrhea (20.4 percent), injection site reaction (19.7 percent), nausea (19.7 percent) and anemia (17.8 percent). The most common Grade 3 or 4 TEAEs (greater than or equal to 5 percent) included neutropenia (14.6 percent), anemia (10.2 percent), neutrophil count decrease (6.4 percent), and thrombocytopenia (5.7 percent). The observed Grade 3 CRS was 2.5 percent. No Grade 4/5 CRS was observed.

"The epcoritamab data suggests a potentially compelling clinical profile for patients with relapsed/refractory LBCL, which currently have limited treatment options," said Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie. "Our partnership with Genmab allows us to continue exploring new standards of care for patients with blood cancer."

Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ broad oncology collaboration. The companies remain committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy for a variety of hematologic malignancies, including an ongoing phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (NCT: 04628494).

About Large B-cell Lymphoma (LBCL)
LBCL is a fast-growing type of non-Hodgkin’s lymphoma (NHL) – a cancer that develops in the lymphatic system – that affects B-cell lymphocytes, a type of white blood cell. There are an estimated 150,000 new LBCL cases each year globally. LBCL includes DLBCL, which is the most common type of NHL worldwide and accounts for approximately 31 percent of all NHL cases.1,2,3,4

About the EPCORE NHL-1 Trial
EPCORE NHL-1 an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL, including LBCL and DLBCL, the most common subtype of LBCL. The dose escalation findings, which determined the recommended phase 2 dose, were published in The Lancet in 2021. In the phase 2 expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who had limited therapeutic options.

The primary endpoint of the phase 2 expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were evaluated as secondary efficacy endpoints.

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.5 CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.6,7 Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit View Source

On June 10, 2022 Zai Lab Limited, a patient-focused, innovative, commercial-stage, global biopharmaceutical company, reported that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted two Breakthrough Therapy Designations for investigational repotrectinib for the treatment of patients with ROS1-positive metastatic NSCLC who have received one prior line of ROS1 TKI and one prior line of platinum-based chemotherapy (EXP-2) and for those with ROS1-positive metastatic NSCLC who have received one prior line of ROS1 TKI and no chemotherapy or immunotherapy (EXP-4) (Press release, Zai Laboratory, JUN 10, 2022, View Source [SID1234633496]). The Breakthrough Therapy Designations for repotrectinib were supported by the data from both global and Chinese TKI-pretreated ROS1-positive NSCLC patients enrolled in the Phase 1/2 TRIDENT-1 study.

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"Since repotrectinib received Breakthrough Therapy Designation by the CDE earlier this year for ROS1-positive TKI-naïve patients, today’s recognition further supports repotrectinib as a potential best-in-class treatment for ROS1-positive NSCLC in both TKI-naïve and pretreated patients in China," said Alan Sandler, M.D., President and Head of Global Development, Oncology at Zai Lab. "There remain significant unmet needs for ROS1-positive NSCLC patients, and we look forward to our continued partnership with regulatory authorities in China to bring this important medicine to patients in need as soon as possible."

The Breakthrough Therapy Designation review policy is designed to facilitate the development and expeditious review of novel medicines that are intended for the prevention or treatment of serious, life-threatening diseases or diseases that severely impact the quality of life for which there is no existing treatment, or where sufficient evidence indicates advantages of the novel drug over currently available treatment options. Drugs granted Breakthrough Therapy Designations receive priority communications and guidance from the CDE to promote and expedite the drug development process.

Lung cancer is both the most commonly diagnosed cancer type and the leading cause of cancer death in China. The incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths1. NSCLC accounts for approximately 85% of lung cancer, and about 70% of NSCLC is locally advanced or metastatic at initial diagnosis. In China, ROS1 rearrangements occur in 2-3% of patients with advanced NSCLC.

1Globocan 2020.

About Repotrectinib

Repotrectinib is a next-generation kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of NSCLC and advanced solid tumors. Tumors with mutations to their ROS1 and NTRK genes have a higher likelihood of developing resistance to existing targeted therapies. In many cases, these mutations prevent existing medicine from targeting and binding to the tumor as effectively as tumors that do not carry the mutations. Repotrectinib is designed to be smaller and less bulky than existing targeted therapies and may circumvent some of the resistance mechanisms found in tumors with ROS1 and NTRK mutations. Zai Lab and Turning Point Therapeutics, Inc. are studying repotrectinib in TRIDENT-1, a registrational Phase 1/2 study in adults, and CARE, a Phase 1/2 study in pediatric patients. The compound has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. Zai Lab is enrolling patients in the registrational Phase 2 portion of TRIDENT-1 in Greater China, while Turning Point Therapeutics is enrolling patients in other regions of the world.

Repotrectinib has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration in: ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK TKIs, with or without prior chemotherapy, and have no satisfactory alternative treatments; and ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and who have not received prior platinum-based chemotherapy. Additionally, repotrectinib was previously granted four Fast-Track designations in: ROS1-positive advanced NSCLC patients who are ROS1 TKI naïve; ROS1-positive advanced NSCLC patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior ROS1 TKI; ROS1-positive advanced NSCLC patients pretreated with one prior ROS1 TKI without prior platinum-based chemotherapy; and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have no satisfactory alternative treatments. Repotrectinib was also granted an Orphan Drug designation in 2017.

Zai Lab has an exclusive license agreement with Turning Point Therapeutics to develop and commercialize repotrectinib in Greater China.

On June 10, 2022 Ratio Therapeutics Inc. reported its launch with a mission to develop best-in-class targeted radiopharmaceuticals for the treatment of cancers (Press release, Ratio Therapeutics, JUN 10, 2022, View Source [SID1234633188]). Founded by entrepreneurial scientists Jack Hoppin, Ph.D., and John Babich, Ph.D., Ratio emerges from stealth mode with more than $20 million in seed funding, fully funded development alliances with Bayer AG and Lantheus Holdings Inc., a robust portfolio of assets developed with two proprietary technologies, and a growing team of world-class experts in radiopharmaceuticals discovery and development. The company’s near-term plans call for the submission of its first investigational new drug (IND) applications, which are expected this quarter, and the initiation of clinical trials later this year. Based in Boston, Ratio is set to move to a new 19,000-square-foot headquarters and research facility in the Seaport District in January.

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Ratio’s radiopharmaceuticals strategy is focused on optimizing tumor localization while minimizing uptake by normal tissues. To achieve this, the company uses its proprietary technology platform called Trillium that is based on Dr. Babich’s prior research at Weill-Cornell Medical College and first developed and validated by the founders in a previous venture. Trillium is a trifunctional small molecule scaffold that can be fine-tuned to alter its plasma clearance, target affinity and therapeutic payload. Each component of the scaffolding can be independently optimized to boost tumor uptake over normal tissue uptake, thereby maximizing therapeutic index. Ratio has successfully applied this framework to several tumor targets and multiple therapeutic payloads.

In addition, Ratio is developing a technology platform to take advantage of the tumor killing power of the alpha emitter, Actinium-225. This proprietary technology is called the Macropa chelate platform. Ratio’s scientists have already successfully incorporated Macropa into the Trillium platform as well as several peptides and antibodies. Macropa’s unique chemistry enables ease of manufacture and robust in vitro and in vivo stability of the resulting radiotherapeutic compound.

"The ability to fine-tune our targeted radiotherapeutics using Trillium and Macropa enables us to address head-on the trifecta of typical challenges we see with most radiopharmaceuticals: delivery, safety and efficacy," said Dr. Babich, Ratio’s President and Chief Scientific Officer. "Over the past year, we have generated significant preclinical data that demonstrate our ability to create excellent performing drug candidates that now are advancing into the clinic. Our goal is to become the partner of choice for pharmaceutical companies committed to this area of cancer therapy by enabling the optimization of a broad array of targeting compounds. We will shepherd these therapies through early clinical studies on our own or in collaboration."

Dr. Hoppin, Ratio’s Chairman and Chief Executive Officer, added, "Targeted radiotherapy is an exciting and emerging field where chemistry meets physics meets medicine. We have assembled and will continue to build a world-class interdisciplinary team of researchers and developers with a singular focus on delivering these treatments to cancer patients. It isn’t often that a start-up company has in place the early financial backing and industry support to advance entirely new drug discoveries to clinical development at this pace. It is with great pride that we announce our formal launch and exit from stealth mode."

In collaboration with Bayer, Ratio has leveraged its Trillium platform for the identification of lead prostate-specific membrane antigen (PSMA)-targeted therapeutic compounds for prostate cancer. At the same time, Ratio is working with Lantheus to develop a lead fibroblast activation protein (FAP)-targeted PET diagnostic compound for a broad array of epithelial-derived cancers, such as breast, pancreatic, lung and stomach cancer. Both collaborations are fully funded and reflect the types of partnerships that Ratio is currently pursuing with other companies.

On June 10, 2022 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it is presenting new long-term follow-up results and subanalyses from clinical trials of its approved therapies, as well as data on investigational medicines from its broad blood cancer portfolio, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress in Vienna (Press release, Hoffmann-La Roche, JUN 10, 2022, View Source [SID1234616240]). Data include five-year results from the phase III CLL14 study of fixed-duration Venclexta/Venclyxto (venetoclax) plus Gazyva/Gazyvaro (obinutuzumab) in previously untreated chronic lymphocytic leukaemia (CLL); the final analysis of the phase III GALLIUM study of Gazyva/Gazyvaro plus chemotherapy in people with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the phase III POLARIX study of Polivy (polatuzumab vedotin) in combination with MabThera/Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Roche will also present data from its T-cell engaging bispecific antibody development programmes including Lunsumio (mosunetuzumab) and glofitamab in patients receiving later lines of therapy for non-Hodgkin lymphoma (NHL) and investigational medicines cevostamab and RG6234 in relapsed or refractory (R/R) multiple myeloma (MM).

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"Blood cancers remain challenging to treat at all stages, but by improving frontline treatment options we aim to increase the likelihood of meaningful clinical outcomes for these patients," said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care."

Improving clinical outcomes with effective frontline treatment options
Five-year results of phase III CLL14 study of Venclexta/Venclyxto plus Gazyva/Gazyvaro (Abstract #S148)
After a median of 65.4 months following treatment with Venclexta/Venclyxto plus Gazyva/Gazyvaro, results confirm the combination continues to be an effective fixed-duration and chemotherapy-free option for patients with previously untreated CLL and coexisting conditions. The estimated investigator-assessed progression-free survival (PFS) rate at this follow-up was 62.6% with Venclexta/Venclyxto plus Gazyva/Gazyvaro and 27.0% with Gazyva/Gazyvaro plus chlorambucil, and the estimated overall survival (OS) rate was 81.9% versus 77.0% (HR 0.72; 95% CI: 0.48-1.09; p=0.12). In addition, the analysis found that 72.1% of patients in the Venclexta/Venclyxto plus Gazyva/Gazyvaro arm did not require another treatment for CLL in the five years following initial treatment (HR 0.42; 95% CI: 0.31-0.57; p<0.0001). No new safety signals were observed.[1] The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

Final analysis of phase III GALLIUM study of Gazyva/Gazyvaro (Abstract #S206)
After eight years of follow-up in people with previously untreated FL, a meaningful improvement in PFS was maintained with Gazyva/Gazyvaro plus chemotherapy, confirming its role as a standard of care for first-line treatment. Seven-year investigator-assessed PFS was significantly improved with Gazyva/Gazyvaro plus chemotherapy (63.4%) compared with MabThera/Rituxan plus chemotherapy (55.7%; HR 0.77; 95% CI: 0.64-0.93; p=0.006). This translated into a longer time to next anti-lymphoma treatment. At seven years, 74.1% of patients receiving Gazyva/Gazyvaro plus chemotherapy had not started new anti-lymphoma therapy compared to 65.4% receiving MabThera/Rituxan plus chemotherapy (HR 0.71; 95% CI: 0.58–0.87; p=0.001). The incidence of serious adverse events was 48.9% with Gazyva/Gazyvaro plus chemotherapy and 43.4% with MabThera/Rituxan plus chemotherapy.[2]

Subgroup analyses of pivotal phase III POLARIX study (Abstract #P1192)
Exploratory subgroup analyses of the phase III POLARIX study of Polivy with R-CHP compared to the current standard of care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated DLBCL further support the potential for Polivy to transform the standard of care for people with this aggressive type of lymphoma. One of the datasets being presented is an analysis of study participants from Asia (China, Hong Kong, Japan, South Korea and Taiwan). Among this subgroup, results showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP, reducing the risk of disease progression, relapse or death by 36% (HR 0.64; 95% CI: 0.40-1.03). The safety profile was generally comparable for both regimens.[3]

Based on the positive POLARIX results from the overall study population, the European Commission (EC) approved Polivy plus R-CHP in May 2022 for the treatment of adult patients with previously untreated DLBCL.

Providing novel bispecific antibodies for patients receiving later lines of therapy in lymphoma and beyond
Pivotal data from phase II NP30179 expansion study of glofitamab (Abstract #S220)
The pivotal phase II NP30179 expansion study included patients with heavily pre-treated and highly refractory DLBCL and showed fixed-duration glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, induced high and durable complete response (CR) rates. After a median follow-up of 12.6 months, 39.4% of patients (n=61/155) achieved a CR (primary efficacy endpoint) and half of them (51.6%; n=80/155) achieved an overall response (the percentage of patients with a partial or CR; secondary efficacy endpoint), as assessed by an independent review committee. Cytokine release syndrome (CRS) was the most common adverse event, occurring in 63.0% of patients.[4] These data were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting and have been submitted for approval to the European Medicines Agency (EMA). Submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are planned this year.

Subgroup analysis and Lunsumio retreatment from pivotal phase II GO29781 study (Abstracts #P1126 and #P1124)
An exploratory subgroup analysis showed Lunsumio could be an efficacious and tolerable option in patients aged <65 and ≥65 years who had R/R FL and had received two or more prior therapies. Patients ≥65 years old achieved a higher objective response rate (ORR) than those <65 years old (87.0% vs 77.0%, respectively). Lower rates of CRS and serious adverse events were observed in patients ≥65 years old (37%) compared to those <65 years old (52%).[5] Additional data from the GO29781 study showed that retreatment with Lunsumio in patients who achieved a CR but whose disease subsequently progressed was effective and the safety of retreatment was consistent with initial treatment.[6]

The EC recently approved Lunsumio for the treatment of people with R/R FL who have received at least two prior systemic therapies.

The data being presented at EHA (Free EHA Whitepaper), as well as phase III studies currently underway, will expand the understanding of glofitamab and Lunsumio and their impact in both later and earlier lines of treatment, with the aim of providing robust and durable treatment outcomes for people with different types of lymphomas.

Early data from novel investigational bispecific antibodies in R/R MM (Abstracts #P962 and #S180)
In line with Roche’s commitment to improving outcomes and personalising care for people with blood cancer, the company has expanded beyond lymphoma and leukaemia, evaluating two investigational medicines in MM. This is the third most common type of blood cancer, diagnosed in more than 170,000 people around the world each year and involves plasma cells (antibody-producing cells in the bone marrow).[7,8] Although advances in treatment have improved outcomes, MM remains an incurable disease characterised by multiple relapses, with an overall five-year survival rate of about 55%.[9] Roche is presenting data at EHA (Free EHA Whitepaper) on cevostamab, an investigational FcRH5xCD3 T-cell engaging bispecific antibody that is being evaluated as a monotherapy and in combination with other medicines to treat people with R/R MM, and on RG6234, a novel GPRC5DxCD3 T-cell engaging bispecific antibody that is being studied in a phase I trial in people with R/R MM. While early, the clinical activity and safety profiles observed with these molecules look encouraging and support further exploration.[10,11]

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to help restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood cancers.

In the US, Venclexta has been granted six Breakthrough Therapy Designations by the U.S. Food and Drug Administration: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL, two for previously untreated acute myeloid leukaemia, and one for myelodysplastic syndromes.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body’s immune system. Gazyva/Gazyvaro is part of a collaboration between Roche and Biogen.

In the US, Europe and multiple other countries, Gazyva/Gazyvaro is currently approved in combination with chlorambucil for patients with previously untreated chronic lymphocytic leukaemia (CLL). It is also approved in combination with bendamustine, followed by Gazyva/Gazyvaro maintenance for the treatment of follicular lymphoma (FL) patients who did not respond to a MabThera/Rituxan (rituximab)-containing regimen, or whose FL returned after such treatment and in combination with chemotherapy for previously untreated advanced FL.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies.[12,13] Polivy is designed to bind to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.[14,15] Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

About Roche’s investigational CD20xCD3 bispecifics in haematology
Roche is currently developing two CD20xCD3 T-cell engaging bispecific antibodies, Lunsumio (mosunetuzumab) and glofitamab, designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Lunsumio and glofitamab differ in their structures, and both are being developed by Roche as part of our ongoing strategy to explore multiple bispecific formats in order to identify those that maximise potential clinical benefits for patients. Lunsumio has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format that we call ‘2:1,’ which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions that bind to CD20 and one ‘Fab’ region that binds to CD3. The clinical development programmes for Lunsumio and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines for the treatment of people with CD20-positive B cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma.