On December 11, 2021 Orca Bio, a clinical-stage biotechnology company developing purified, high-precision cell therapies for the treatment of cancer, autoimmune diseases and genetic blood disorders, reported positive clinical data on its lead investigational cell therapy, Orca-T, were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Orca Bio, DEC 11, 2021, View Source [SID1234596852]). The data presented on 109 patients with at least 90 days of follow-up in combined data from the Phase 1b and Phase 2 trials showed significantly higher graft-versus-host disease-free, relapse-free survival (GRFS) rates compared to patients who received standard of care.

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"The lower rates of graft versus host disease and improved relapse-free survival suggest Orca-T has the potential to become a safer and more effective treatment option for patients living with serious blood cancers," said Ivan Dimov, Ph.D., cofounder and chief executive officer of Orca Bio. "We are further encouraged by the validation of our platform as we advance Orca-T into our pivotal Phase 3 trial, a significant step toward potential commercialization and, most importantly, to helping more patients in need."

Findings presented today in an oral presentation included pooled results from the single-center Phase 2 and multi-center Phase 1b trials from 109 patients with acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndromes, myelofibrosis and other hematological malignancies. Median follow-up for these patients was 617 days (single-center) and 209 days (multi-center). For comparison purposes, a contemporary, propensity-matched cohort of 95 matched patients undergoing standard of care allogeneic hematopoietic stem cell transplant (alloHSCT) served as the standard of care cohort ("SOC cohort"). Results demonstrated that:

Patients who received Orca-T had a GRFS of 74%. When comparing this non-randomized data to the SOC cohort, the difference was significant (74% vs. 34%; p<0.0001).
Orca-T showed the potential for lower rates of moderate-to-severe chronic graft versus host disease (GvHD) at 1 year post-transplant (3% vs. 43%; p<0.0005).
Overall survival rates with Orca-T (90% vs. 78%; p<0.03) and rates of chronic-GvHD-free survival (87% vs. 45%; p<0.0001) were improved.
Orca-T was manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the continental U.S.
In a poster presentation at ASH (Free ASH Whitepaper), Orca Bio also shared an analysis of treatment impact in patients with myelofibrosis. The analysis compared eight patients with myelofibrosis who were treated with Orca-T with six patients who underwent standard of care (SOC) alloHSCT. Regression of marrow fibrosis to myelofibrosis grade 0 or 1 was observed by Day 100 post-transplant in all eight Orca-T recipients, but was observed in only one of the six SOC patients. Additionally, Orca-T recipients had lower incidence of acute and chronic GvHD.

Along with the positive Phase 1b/2 results, Orca Bio announced that it has completed a successful end of Phase 2 meeting with the U.S. Food and Drug Administration and plans to commence a Phase 3 trial for Orca-T in early 2022.

The full presentation is available on www.orcabio.com.

About Orca-T
Orca-T is an investigational high-precision allogeneic cellular therapy consisting of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and is being studied to treat multiple hematologic malignancies.

On December 11, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that new analyses illustrating responses that first-line treatment with DARZALEX▼ (daratumumab)-based regimens may be able to achieve, including a potential survival benefit for daratumumab in combination with lenalidomide and dexamethasone (Rd).1,2 Updated data from the randomised Phase 2 GRIFFIN study in transplant-eligible patients and real-world evidence in transplant-ineligible patients were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting (Press release, Johnson & Johnson, DEC 11, 2021, View Source [SID1234596850]). Data from the GRIFFIN study will also be featured in the Highlights of ASH (Free ASH Whitepaper) programme.

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"Despite treatment advances, multiple myeloma remains a complex, currently incurable blood cancer. The latest clinical trial data and real-world evidence presented for daratumumab at ASH (Free ASH Whitepaper) shines a light on the potential of daratumumab-based combinations and sequencing approaches in the first-line, to tackle this complexity and improve patient outcomes," said Edmond Chan MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "At Janssen, we are committed to developing transformative treatment regimens that address individual patient needs and offer physicians options which they have not had before, as we work towards our longer-term goal of curing multiple myeloma."

Updated Phase 2 GRIFFIN data of investigational daratumumab quadruple regimen for newly diagnosed transplant-eligible patients1

Updated results from the GRIFFIN study, now with a median follow-up of 38.6 months, were presented in an oral session (Abstract #79). The data show improved outcomes with the addition of daratumumab to bortezomib (VELCADE), lenalidomide (Revlimid) and dexamethasone (VRd), followed by daratumumab plus lenalidomide (R) maintenance therapy, in transplant-eligible patients.1 Key findings included:

The rate of stringent complete response (sCR) favoured daratumumab-VRd compared to VRd alone (66 percent versus 47.4 percent; p=0.0096).1,3
Minimal residual disease (MRD) negativity rates at a threshold of 10-5 remained significantly higher in patients treated with daratumumab-VRd versus VRd alone (64.4 percent versus 30.1 percent; p<0.0001).1, 3
Whilst this study was not powered for progression-free survival (PFS), at 36 months, the PFS rate trended toward favouring daratumumab-VRd compared to VRd alone (88.9 percent versus 81.2 percent).1
At the median follow-up of 38.6 months, median progression-free survival (mPFS) had not been reached in either arm.1
No new safety concerns were observed with longer-term follow up.1
"These updated findings from the GRIFFIN study are promising when adding daratumumab to VRd in the treatment of newly diagnosed, transplant-eligible multiple myeloma," said Jacob Laubach†, M.D., M.P.P, Clinical Director of the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and GRIFFIN study investigator.

Additional analyses of daratumumab-based regimens for the treatment of transplant-ineligible newly diagnosed multiple myeloma2

Research shows that 50 percent of transplant-ineligible patients will not receive a second line of therapy.2 An oral presentation at ASH (Free ASH Whitepaper) 2021 highlighted clinical sequencing scenarios in patients with newly diagnosed transplant-ineligible multiple myeloma, utilising data from the Phase 3 MAIA study, including attrition rates, and real-world evidence from the Flatiron Health electronic health record-derived de-identified database* (Abstract 118).2 Researchers explored survival outcomes based on clinical sequencing scenarios using daratumumab first in combination with Rd, compared to when bortezomib was administered first in combination with Rd.2 Results from this modelled analysis suggest a potential for a survival benefit when patients received daratumumab in first-line treatment versus saving it for later.2 Future research is required to generate clinical data to confirm these results.2

A second presentation of real-world evidence data provided additional insights on sequencing, based on results from a retrospective, observational cohort study evaluating patients from the Flatiron database who received first-line daratumumab-Rd (Abstract #1979).4 The analysis indicated that the real-world patient population was similar to that of the MAIA study population, with an early trend of PFS similar to that observed in the MAIA study.4

A post-hoc analysis of the Phase 3 MAIA study, focusing on patients with renal impairment, was highlighted in a poster presentation (Abstract #1646).5 Research shows that approximately 20 to 50 percent of patients with multiple myeloma have baseline renal impairment that can impact their choice of treatment and efficacy.5 The exploratory analyses presented at ASH (Free ASH Whitepaper) showed that PFS and overall survival (OS) benefits were observed in these patients who were treated with daratumumab-Rd compared to Rd alone, regardless of the lenalidomide starting dose.5 OS data from the MAIA study were recently published in The Lancet Oncology.

"The clinical data presented at ASH (Free ASH Whitepaper) support daratumumab as a foundational therapy for patients with newly diagnosed multiple myeloma in transplant-ineligible populations," said Imran Khan, M.D., Ph.D., U.S. Vice President, Medical Affairs, Hematology, Janssen Scientific Affairs, LLC. "Real-world evidence about efficacy, safety and adherence is becoming increasingly important for clinicians in optimising treatment approaches for patients with multiple myeloma. We will continue to advance research that can provide important insights about daratumumab as part of a standard of care regimen in the frontline setting."

#ENDS#

About the GRIFFIN Study1,6

The Phase 2 GRIFFIN (NCT02874742) study evaluated the investigational regimen of daratumumab in combination with VRd and enrolled and treated more than 200 adults aged 18–70 years with newly diagnosed multiple myeloma (NDMM) and who were eligible for high-dose therapy/autologous stem cell therapy (ASCT).6

In the safety run-in cohort, patients received 25 mg of lenalidomide orally on Days 1–14; 1.3 mg/m2 of bortezomib subcutaneously on Days 1, 4, 8 and 11; and 20 mg of dexamethasone on Days 1, 2, 8, 9, 15 and 16, every 21 days during the induction and consolidation phases (Cycles 1–6).1 Daratumumab 16 mg/kg IV was given on days 1, 8 and 15 of Cycles 1–4 and on day 1 of Cycles 5–6.1

During the maintenance phase (Cycles 7–32), patients received 10 mg daily of lenalidomide (15 mg beginning at Cycle 10 if tolerated) on days 1–21 every 28 days and daratumumab 16 mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical pharmacokinetic data demonstrating improved target saturation with every four-week maintenance dosing.1 Maintenance therapy with lenalidomide may be continued beyond Cycle 32 in both arms, per local standard of care.1

In the subsequent randomised Phase 2 portion of the study, 207 patients were randomised and received treatment with VRd induction and consolidation, ASCT, and maintenance therapy with lenalidomide; or daratumumab and VRd, ASCT, and maintenance therapy with daratumumab and lenalidomide.1

About the MAIA Study7

The randomised, open-label, multicentre Phase 3 MAIA study (NCT02252172) included 737 newly diagnosed patients with multiple myeloma ineligible for high-dose chemotherapy and ASCT, aged 45–90 years (median age of 73).7 Patients were randomised to receive either daratumumab-Rd or Rd alone in 28-day cycles. In the daratumumab-Rd arm, patients received daratumumab 16 mg/kg IV weekly for Cycles 1–2, every two weeks for Cycles 3–6 and every four weeks for Cycle 7 and thereafter.7 Patients in both treatment arms received 25 mg of lenalidomide on Days 1–21 of each 28-day cycle, and dexamethasone at 40 mg once a week.7 Patients in both treatment arms continued until disease progression or unacceptable toxicity.7

Earlier results from the MAIA study supported the European Commission (EC) approval of daratumumab in combination with Rd, marking the first approval of a CD38 monoclonal antibody for patients with transplant-ineligible NDMM. These data were also published in The New England Journal of Medicine in 2019.

Modelling and Real-World Data Limitations

Modelling and real-world data have the potential to supplement randomised controlled trial data by providing additional information about how a medicine performs across all available Phase 2 and 3 clinical trials and in routine clinical practice. There are limitations, however, and these data cannot be used as stand-alone evidence to validate the efficacy or safety of a treatment.

*The Flatiron Health database is a longitudinal database comprising de-identified, patient-level structured and unstructured data curated via technology-enabled abstraction.

About daratumumab

Janssen is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease. Daratumumab has been approved in eight indications for multiple myeloma, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.8

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 227,000 patients worldwide.9 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. Daratumumab subcutaneous (SC) formulation is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.10

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.8 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.8 Daratumumab may also have an effect on normal cells.8 Data across eight Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in PFS and/or OS.11,12,13,14,15,16,17,18

For further information on daratumumab, please see the Summary of Product Characteristics at: View Source

About Multiple Myeloma

Multiple myeloma is currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.19 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow.20 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.20 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.21

On December 11, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, reported that clinical updates on omidubicel in two presentations on the first day of the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Atlanta, Georgia and virtually December 11-14, 2021 (Press release, Gamida Cell, DEC 11, 2021, View Source [SID1234596849]).

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In an oral presentation titled "Hematopoietic Stem Cell Transplantation (HSCT) with Omidubicel is Associated with Robust Immune Reconstitution and Lower Rates of Severe Infection Compared to Standard Umbilical Cord Blood Transplantation," Gamida Cell shared data from an analysis of a subset of 37 patients from the Phase 3 randomized trial of omidubicel. The analysis was aimed at investigating the reduced infection rates observed in the study and showed that the omidubicel-treated patients had more rapid recovery of a wide variety of immune cells including CD4+ T cells, B cells, NK cells and dendritic cell subtypes. The robust recovery of the immune system provides rationale for fewer severe bacterial, fungal and viral infections in patients treated with omidubicel. Further analyses are ongoing to further characterize the immune recovery following omidubicel transplantation.

"These results demonstrating rapid and functional reconstitution of the immune cells – particularly the T cell recovery which is known to lag in cord blood transplants – provides mechanistic support for the lower rates of severe infection observed in the omidubicel-treated patients," said Paul Szabolcs, M.D., Division of Blood and Marrow Transplantation and Cellular Therapy, UPMC Children’s Hospital of Pittsburgh. "These data provide encouraging support for patients suffering from blood cancers who are particularly vulnerable to devastating infections following transplant."

An additional poster presentation unveiled today, "Allogeneic Stem Cell Transplantation with Omidubicel: Long-Term Follow-up from a Single Center," includes outcomes of 22 patients in the Phase 1 and 2 studies of omidubicel at Duke University over a 10-year period and shows long-term sustained bone marrow function and immune recovery. With a median follow-up of 2.3 years the estimated 10-year overall survival (OS) is 48.5% and disease-free survival (DFS) is 43.6%, with no major and or unexpected long-term complications. Durable hematopoiesis was observed at up to 10 years with one case of secondary graft failure and no secondary malignancies.

"Following our positive Phase 3 study results that showed enhanced hematopoietic recovery with omidubicel, it is extremely encouraging to see these additional data that demonstrate the durability of the graft, providing long-term recovery of the hematopoietic system," said Ronit Simantov, M.D., Chief Medical Officer of Gamida Cell. "The analyses presented at ASH (Free ASH Whitepaper) build on our understanding of the clinical benefits of omidubicel and provide compelling evidence of its potential to change the outlook for a patient population in dire need of enhanced treatment options."

Gamida Cell will present additional clinical updates at ASH (Free ASH Whitepaper) including two-year survival data for GDA-201, the company’s lead NAM-enabled NK cell therapy, and an analysis of hospital and healthcare resource use for patients treated with omidubicel compared to cord blood transplantation. Both poster presentations will be publicly available on Monday, Dec. 13.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with blood cancers. Omidubicel is the first bone marrow transplant graft to receive Breakthrough Therapy Designation from the U.S. FDA and has also received Orphan Drug Designation in the U.S. and EU. For more information about omidubicel, please visit View Source

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

On December 11, 2021 City of Hope reported that data from an investigational Phase 1/2, single arm trial using a bispecific antibody called mosunetuzumab highlights the paradigm-changing potential of a new treatment option for people with follicular lymphoma, a type of blood cancer and the most common indolent form of non-Hodgkin lymphoma (NHL) (Press release, City of Hope, DEC 11, 2021, View Source [SID1234596848]). Patients within the trial achieved high response rates with 80% of patients responding positively to the treatment, and 60% had a complete response, meaning the cancer could not be detected.

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"Our study demonstrated that an antibody based on bispecific T cell engaging technology is proving to work very well with high response rates — and safely — in blood cancer patients who need more effective therapies and with fewer side effects," said Elizabeth Budde, M.D., Ph.D., associate professor, City of Hope Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, who discussed the results today at an ASH (Free ASH Whitepaper) press briefing. "Mosunetuzumab is a very promising therapy, showing deep and durable responses for patients whose lymphoma has relapsed or is no longer responding to currently available therapies."

Instead of concentrating on a singular target, "bispecific" antibodies are therapeutics that act on two cellular targets simultaneously. In the case of mosunetuzumab, one "arm" targets the CD3 protein on T cells, an immune cell that can help in the fight against cancer if engaged; a second "arm" binds to CD20, a protein commonly found on lymphoma cells.

"The two cell groups are pulled together, with mosunetuzumab serving as a kind of bridge," Budde said. "Being in such close proximity allows the now activated T cells to better recognize and attack the lymphoma cells."

Ninety patients with follicular lymphoma, who ranged in age from 29 to 90 years old, were enrolled in the multicenter international trial. The patients received mosunetuzmab, a Genentech medicine, intravenously every 21 days for a minimum of eight cycles and up to 17 cycles.

The median time to first response was 1.4 months. With a median follow up of 17.8 months, 70% patients with response continued to do well.

Cytokine release syndrome was a side effect in 44% of patients. Most were low grade and occurred during the first cycle. All resolved completely. Other side effects included fatigue and headache. Only two patients discontinued treatment due to mosunetuzumab-related side effects.

Genentech, a member of the Roche Group, plans to submit this new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be the first CD20xCD3 T cell engaging bispecific antibody approved for NHL.

Renee Bentson, 69, of Covina, California, was one of the first participants in the trial at City of Hope. Before she was diagnosed with cancer, Bentson, who was physically active and running seven miles a day, began to notice a rash, chest pain and night sweats. When an unusual fatigue set in and lumps began to appear, first on one side of her torso, then the other and on one arm, Bentson consulted a doctor, who promptly ordered a biopsy.

Bentson was diagnosed with follicular lymphoma, which makes up about 20% of all lymphoma cases. It tends to strike older people, and though it does respond to initial treatment, it is not curable with convention therapy and relapse is frequent. Remission duration tends to get shorter with each subsequent relapse after treatment.

While some patients do well on chemotherapy, Bentson was concerned about the potential side effects. She participated in a series of immunotherapy clinical trials. The cancer would shrink, but not disappear, and later it would recur. With mosunetuzumab, which was her fourth line of treatment, the cancer went into remission in early 2017 and she has been cancer free since then.

"I’m just so grateful that it worked," said Bentson, who experienced few side effects from the treatment.

City of Hope is a leader in blood cancer immunotherapies. The National Cancer Institute-designated comprehensive cancer center has performed more than 17,000 bone marrow/stem cell transplants and is a leader in chimeric antigen receptor (CAR) T therapy, with nearly 800 patients treated with immune effector cells, including CAR T therapy, and nearly 80 open or completed trials.

On December 11, 2021 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new pivotal data on its CD20xCD3 T-cell engaging bispecific antibody, mosunetuzumab, will be presented for the first time at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition from December 11-14, 2021 (Press release, Genentech, DEC 11, 2021, View Source [SID1234596847]).

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Emerging data continue to show the promising benefit-risk profile of mosunetuzumab in relapsed or refractory (R/R) follicular lymphoma (FL), a slow-growing, or indolent, form of non-Hodgkin’s lymphoma (NHL). Pivotal results from the Phase I/II GO29781 study demonstrated that mosunetuzumab induces durable complete responses lasting at least 18 months in heavily pretreated patients with R/R FL who have received two or more prior therapies, with a 60.0% complete response (CR) rate and a median progression-free survival of 17.9 months (95% CI: 10.1-not evaluable). Median duration of response was 22.8 months among responders (95% CI: 9.7-not evaluable). The most common adverse event (AE) was cytokine release syndrome (CRS), which was generally low grade (mainly Grade 1-2).

"Despite initial successful treatment, many people with follicular lymphoma often experience relapse. Mosunetuzumab could potentially become a highly efficacious treatment option that can be administered without the need for cell collection or genetic engineering," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "With mosunetuzumab, we also aim to offer a therapy that can be administered in the outpatient setting to people with this devastating blood cancer."

Genentech plans to submit the new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL. Roche recently submitted the initial marketing authorization application for mosunetuzumab to the European Medicines Agency, with the hope to bring this drug as soon as possible to people with NHL.

Additionally, as part of Genentech’s broad pipeline of hematology immunotherapies and application of novel combinations, key data for the bispecific antibodies mosunetuzumab, glofitamab and cevostamab are being presented, including:

Initial results from the Phase Ib CO41942 study of mosunetuzumab in combination with lenalidomide in people with R/R FL who have received at least one prior line of therapy demonstrated encouraging preliminary efficacy and a tolerable safety profile.
Data from the Phase Ib/II GO40516 study evaluating mosunetuzumab in combination with Polivy (polatuzumab vedotin-piiq) showed promising efficacy and favorable safety in heavily pretreated patients with aggressive R/R NHL with an objective response rate (ORR) of 65.0% and a CR rate of 48.3%. CRS occurred in 18% of patients, and all events occurred in Cycle 1 and were Grade 1-2.
A Phase I/Ib NP30179 dose-escalation study evaluating glofitamab as a monotherapy and in combination with Gazyva (obinutuzumab) following pretreatment with Gazyva in patients with R/R B-cell NHL showed promising activity in both R/R FL and R/R mantle cell lymphoma (MCL), an uncommon but aggressive form of lymphoma with poor prognosis for those who progress.
Preliminary results in heavily pretreated patients with R/R FL showed high response rates across all treatment groups, including high-risk subgroups, with an ORR of 81.0% for the glofitamab monotherapy group and an ORR of 100% for the glofitamab plus Gazyva combination therapy group. For patients with R/R MCL treated with glofitamab monotherapy following Gazyva pretreatment, the ORR was 81.0%. Across both studies, the most common AE was CRS, with the majority of events being low grade (Grade 1-2).
Results of the Phase Ib/II NP39488 study of glofitamab in combination with Polivy demonstrated encouraging preliminary efficacy and a tolerable safety profile in people with difficult-to-treat R/R diffuse large B-cell lymphoma. With a median follow up of 3.2 months (95% CI: 1.4-3.5), an ORR of 73.0% was observed with a 51.5% CR rate, with patients showing durable responses at ≥6 months. No Grade 3 or higher CRS events were observed, and the safety profile of the combination was consistent with that of the individual medicines.
Data from the Phase I GO39775 dose-escalation and expansion study investigating cevostamab in heavily pretreated patients with R/R multiple myeloma (MM) showed the first-of-its kind FcRH5xCD3 bispecific antibody induced clinically meaningful, target dose-dependent increases in ORR without an increase in the rate of CRS, with an ORR of 54.5% in the 160 mg dose group. Results from double step-up dosing suggest this approach could help mitigate CRS and potentially improve the safety profile compared to single step-up dosing.
Our investigational cancer immunotherapies, mosunetuzumab and glofitamab, are T-cell engaging bispecific antibodies designed to engage with CD3 on the T cell and CD20 on the tumor cell, bringing them close in proximity and enabling the T cell to eliminate the tumor cell. Although these bispecific antibodies have similar modes of action, they differ in their structure and clinical profiles. Cevostamab, another investigational T-cell engaging bispecific antibody, is designed to target FcRH5 on myeloma cells and CD3 on T cells and is currently being evaluated in people living with R/R MM.

Genentech’s broad and comprehensive clinical development program will continue to evaluate mosunetuzumab, glofitamab and cevostamab as monotherapies and in combination with other established and/or novel therapies for malignant hematological conditions with the goal of providing treatment solutions tailored to the patient journey for each disease.

Keep up to date with ASH (Free ASH Whitepaper) 2021 news and updates by using the hashtag #ASH21 and follow Genentech on Twitter via @Genentech and on LinkedIn.

About Genentech’s Investigational Bispecifics in Hematology

Genentech is currently developing two T-cell engaging bispecific antibodies, 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. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Genentech as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximize potential clinical benefits for patients. Mosunetuzumab 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 which 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 programs for mosunetuzumab 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’s lymphomas), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

About Cevostamab (FcRH5xCD3 Bispecific Antibody)

Cevostamab (BFCR4350A) is an FcRH5xCD3 T-cell engaging bispecific antibody designed to target FcRH5 on myeloma cells and CD3 on T cells. FcRH5 is a unique and differentiated target, expressed on nearly all myeloma cells. Cevostamab 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 FcRH5 and the other ‘Fab’ region targets CD3. This dual targeting activates and re-directs a patient’s existing T cells to engage and eliminate target FcRH5-expressing myeloma cells by releasing cytotoxic proteins into the myeloma cells.

About the GO29781 Study

The GO29781 study [NCT02500407] is a Phase I/II, multicenter, open-label, dose-escalation study evaluating the safety and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include complete response rate (best response) by independent review facility (primary endpoint), objective response rate, duration of response, progression-free survival, and safety and tolerability (secondary endpoints).

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information for additional Important Safety Information.

Gazyva U.S. Indication

Gazyva is a prescription medicine used with the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.

Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life-threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If a patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. If a patient has a weakened immune system, it could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems
Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must contact their healthcare team if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past
Additional possible serious side effects of Gazyva:

Patients must tell their healthcare team right away about any side effect they experience. Gazyva can cause side effects that may become severe or life-threatening, including:

Infusion-related reactions (IRRs): These side effects may occur during or within 24 hours of any Gazyva infusion. Some IRRs can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening IRRs. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the IRR is life-threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of IRRs may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort
Hypersensitivity reactions including serum sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva
Tumor lysis syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness
Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone, are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP
Low white blood cell count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections
Low platelet count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced
The most common side effects seen with Gazyva in a study that included relapsed or refractory FL patients were infusion-related reactions, fatigue, low white blood cell counts, cough, upper respiratory tract infection, and joint or muscle pain.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines
Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, or plan to become pregnant. Gazyva may harm a patient’s unborn baby. The patient should speak to their healthcare team about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. Women of childbearing potential should use effective contraception while taking Gazyva and for 6 months after their Gazyva treatment
Breastfeeding: Because of the potential risk of serious side reactions in breastfed children, women should not breastfeed while taking Gazyva and for 6 months after their last dose
Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source