On December 09, 2024 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new and updated data from its industry-leading CD20xCD3 T-cell-engaging bispecific antibody program were presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, December 7-10, 2024 (Press release, Genentech, DEC 9, 2024, View Source [SID1234648949]). With more than 20 bispecific antibody abstracts accepted for presentation, data showcase the benefits of fixed-duration Columvi (glofitamab-gxbm) and Lunsumio (mosunetuzumab-axgb) across different types of aggressive and indolent lymphomas. This research supports Genentech’s efforts to continue innovating for patients by advancing treatment standards at earlier stages of disease while exploring additional forms of administration that could further improve the patient experience.
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"The data being presented at ASH (Free ASH Whitepaper) offer further evidence that Columvi and Lunsumio can provide lasting remissions for people with advanced lymphoma," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "The results underscore our ambition to transform the treatment of B-cell malignancies with a range of innovative therapeutic options."
"Lymphoma patients face challenges that extend well beyond the clinical manifestations of their disease, including the physical and emotional strain of frequent appointments and treatments," said Elizabeth Budde, M.D., Ph.D., City of Hope’s executive medical director of its Enterprise Immune Effector Cell Program and associate professor in its Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. "While Lunsumio’s fixed-duration intravenous formulation has already offered a valuable treatment option, the introduction of a subcutaneous route could provide a shorter administration time. With both routes available, we can better tailor therapy to each patient’s needs, supporting a flexible and patient-centered approach to follicular lymphoma care."
Follow-up data reinforce benefits of fixed-duration therapies beyond the end of treatment
Three-year follow-up from the pivotal Phase II NP30179 study of Columvi in people with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) showed 40.0% of patients achieved a complete response (CR), with a median duration of CR of 29.8 months (95% CI: 22.0–not estimable [NE]). The majority of patients in complete remission at the end of therapy remained in remission two years after therapy completion. Safety appeared consistent with the previous analysis.
Long-term data at four years from the pivotal Phase II GO29781 study of Lunsumio in patients with R/R follicular lymphoma (FL) showed long-lasting remissions, with nearly two-thirds (64.0% [95% CI: 50.1-78.0]) of patients with a CR alive and without disease progression at 45 months. The overall response rate (ORR) and CR rates in the overall population were 77.8% and 60.0%, respectively. Consistent results were seen in patients with a history of disease progression within 24 months of frontline treatment (POD24), which is typically harder to treat. No new safety signals were observed since the previous analysis.
Both studies also showed restoration of B-cell levels, starting from 12-18 months following Columvi treatment and after a median of 19 months following Lunsumio treatment, indicating immune system recovery and supporting the use of a fixed-duration treatment approach. Recovery of B cells following treatment for lymphoma is important so that patients can maintain immune system function.
A U.S. real-world data study and economic model evaluating R/R non-Hodgkin lymphoma patient treatment-related travel burden across different bispecific antibody therapies highlight the impact of travel distance, time and associated costs, an often-overlooked aspect of the patient experience beyond clinical efficacy and safety. These factors play a crucial role in treatment decision-making, further emphasizing the importance of patient-centered treatment options. The study found fixed-duration therapies, such as Columvi and Lunsumio, reduce treatment-related travel burden due to less frequent dosing.
Studies investigating subcutaneously-administered Lunsumio show positive results
Data from a primary analysis of the Phase II GO29781 study of investigational Lunsumio administered subcutaneously in patients with third-line or later FL were presented for the first time. Results show pharmacokinetic non-inferiority compared to intravenous (IV) administration, with fixed-duration Lunsumio achieving high rates of deep and durable remissions, with 76.6% of patients experiencing an ORR and a 61.7% CR rate, as evaluated by the independent review committee. The median progression-free survival was 23.7 months (95% CI: 14.6-NE), while the median overall survival was not reached. The most common all-grade adverse events (AEs) were injection-site reactions (60.6%; all Grade 1-2), fatigue (35.1%), and cytokine release syndrome (CRS; 29.8%). The rate and severity of CRS events were low (Grade 1-2, 27.6%; Grade 3, 2.1%); all occurred during cycle 1 and were resolved. Data has been submitted to health authorities with the aim of offering patients and healthcare providers an alternative treatment and more choice when it comes to administration options depending on their needs.
New data from a randomized Phase II cohort of the investigational GO40516 study showed improved efficacy and manageable safety with outpatient, subcutaneously administered, fixed-duration Lunsumio in combination with Polivy (polatuzumab vedotin-piiq) versus Rituxan (rituximab) in combination with Polivy, in people with R/R LBCL. In the Lunsumio-Polivy arm, the ORR was 77.5% (95% CI: 61.6-89.2) versus 50.0% (95% CI: 33.8–66.2) for Rituxan-Polivy, and the CR rate was 57.5% (95% CI: 40.9-73.0) versus 35.0% (95% CI: 20.6-51.7). AEs of special interest occurring in ≥30% of patients in the Lunsumio-Polivy arm were injection-site reactions (55.0%) and neutropenia (40.0%). CRS events occurred in four (10.0%) patients, all of which were Grade 1-2, occurred during cycle 1 and were resolved. These data support further exploration of this investigational treatment combination in the ongoing Phase III SUNMO study, which could provide an alternative option in second-line DLBCL to meet diverse patient needs.
Additional data support Genentech’s goal to elevate treatment standards in earlier stages of LBCL
Updated data from the Phase I/Ib investigational NP39488 study showed high and durable response rates in people with R/R LBCL treated with Columvi in combination with Polivy, including those with high-grade disease and prior treatment with CAR T-cell therapy. Of the 128 efficacy-evaluable patients, the best ORR was 80.6%, with a CR rate of 62.0%, and the median duration of CR was 31.8 months (95% CI: 21.9-NE). Among patients previously treated with CAR T-cell therapy (n=28), the ORR was 75.0%, with a CR rate of 50.0%. The safety profile was manageable and consistent with the known profiles of the individual drugs. The most common AE was CRS (44.4%), which was mostly Grade 1-2. Results support ongoing development of this investigational combination in the Phase III SKYGLO study investigating Columvi with Polivy-Rituxan, cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL.
About Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma (NHL) in the U.S. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes. DLBCL not otherwise specified is the most common category of large B-cell lymphoma (LBCL) and accounts for about 80% or more of cases. It applies to cases that do not fall into any specific disease subgroups of LBCL.
About Columvi (glofitamab-gxbm)
Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Genentech’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program that also includes Lunsumio (mosunetuzumab), which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Genentech is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma and mantle cell lymphoma.
Columvi U.S. Indication
Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.
It is not known if Columvi is safe and effective in children.
The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works.
What is the most important information I should know about Columvi?
Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death.
Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:
fever of 100.4°F (38°C) or higher
chills or shaking
fast or irregular heartbeat
dizziness or light-headedness
trouble breathing
shortness of breath
Due to the risk of CRS, you will receive Columvi on a "step-up dosing schedule".
A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1).
You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller "step-up" doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose.
You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2).
If your dose of Columvi is delayed for any reason, you may need to repeat the "step-up dosing schedule".
If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi.
Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.
Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects.
Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.
What are the possible side effects of Columvi?
Columvi may cause serious side effects, including:
Cytokine Release Syndrome.
Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:
headache
confusion and disorientation
difficulty paying attention or understanding things
trouble speaking
sleepiness
memory problems
numbness, tingling, or weakness of the hands or feet
dizziness
shaking (tremors)
Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare:
tender or swollen lymph nodes
pain or swelling at the site of the tumor
chest pain
cough
trouble breathing
The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness.
The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).
Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects.
Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you:
have an infection
have kidney problems
are pregnant or plan to become pregnant. Columvi may harm your unborn baby
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with Columvi.
You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi.
are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What should I avoid while receiving Columvi?
Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.
These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi.
You may report side effects to the FDA at (800) FDA-1088 or View Source You may also report side effects to Genentech at (888) 835-2555.
Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit View Source
About Lunsumio (mosunetuzumab-axgb)
Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody 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. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.
Lunsumio U.S. Indication
Lunsumio (mosunetuzumab-axgb) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer.
It is not known if Lunsumio is safe and effective in children.
The conditional approval of Lunsumio is based on response rate. There are ongoing studies to establish how well the drug works.
What is the most important information I should know about Lunsumio?
Lunsumio may cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Lunsumio and can also be severe or life-threatening.
Get medical help right away if you develop any signs or symptoms of CRS at any time, including:
fever of 100.4°F (38°C) or higher
chills
low blood pressure
fast or irregular heartbeat
tiredness or weakness
difficulty breathing
headache
confusion
feeling anxious
dizziness or light-headedness
nausea
vomiting
Due to the risk of CRS, you will receive Lunsumio on a "step-up dosing schedule."
The step-up dosing schedule is when you receive smaller "step-up" doses of Lunsumio on Day 1 and Day 8 of your first cycle of treatment
You will receive a higher dose of Lunsumio on Day 15 of your first cycle of treatment
If your dose of Lunsumio is delayed for any reason, you may need to repeat the step-up dosing schedule
Before each dose in Cycle 1 and Cycle 2, you will receive medicines to help reduce your risk of CRS
Your healthcare provider will check you for CRS during treatment with Lunsumio and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Lunsumio, if you have severe side effects.
What are the possible side effects of Lunsumio?
Lunsumio may cause serious side effects, including:
neurologic problems. Lunsumio can cause serious and life-threatening neurological problems. Your healthcare provider will check you for neurologic problems during treatment with Lunsumio. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems during or after treatment with Lunsumio, including:
headache
numbness and tingling of the arms, legs, hands, or feet
dizziness
confusion and disorientation
difficulty paying attention or understanding things
forgetting things or forgetting who or where you are
trouble speaking, reading, or writing
sleepiness or trouble sleeping
tremors
loss of consciousness
seizures
muscle problems or muscle weakness
loss of balance or trouble walking
tiredness
serious infections. Lunsumio can cause serious infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with Lunsumio, including:
fever of 100.4° F (38° C) or higher
chest pain
tiredness
shortness of breath
painful rash
sore throat
pain during urination
feeling weak or generally unwell
hemophagocytic lymphohistiocytosis (HLH). Lunsumio can cause overactivity of the immune system, a condition called hemophagocytic lymphohistiocytosis. HLH can be life-threatening and has led to death in people treated with Lunsumio. Your health care provider will check you for HLH especially if your CRS lasts longer than expected. Signs and symptoms of HLH include:
fever
enlarged spleen
easy bruising
low blood cell counts
liver problems
low blood cell counts. Low blood cell counts are common during treatment with Lunsumio and can also be serious or severe. Your healthcare provider will check your blood cell counts during treatment with Lunsumio. Lunsumio can cause the following low blood cell counts:
low white blood cell counts (neutropenia). Low white blood cells can increase your risk for infection
low red blood cell counts (anemia). Low red blood cells can cause tiredness and shortness of breath
low platelet counts (thrombocytopenia). Low platelet counts can cause bruising or bleeding problems
growth in your tumor or worsening of tumor related problems (tumor flare). Lunsumio can cause serious or severe worsening of your tumor. Tell your healthcare provider if you develop any of these signs or symptoms of tumor flare during your treatment with Lunsumio:
chest pain
cough
trouble breathing
tender or swollen lymph nodes
pain or swelling at the site of the tumor
Your healthcare provider may temporarily stop or permanently stop treatment with Lunsumio if you develop severe side effects.
The most common side effects of Lunsumio include: tiredness, rash, fever, and headache.
The most common severe abnormal blood test results with Lunsumio include: decreased phosphate, increased glucose, and increased uric acid levels.
Before receiving Lunsumio, tell your healthcare provider about all of your medical conditions, including if you:
have ever had an infusion reaction after receiving Lunsumio
have an infection, or have had an infection in the past which lasted a long time or keeps coming back
have or have had Epstein-Barr Virus
are pregnant or plan to become pregnant. Lunsumio may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Lunsumio
Females who are able to become pregnant:
your healthcare provider should do a pregnancy test before you start treatment with Lunsumio
you should use an effective method of birth control (contraception) during your treatment and for 3 months after the last dose of Lunsumio
are breastfeeding or plan to breastfeed. It is not known if Lunsumio passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of Lunsumio
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What should I avoid while receiving Lunsumio?
Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems.
These are not all the possible side effects of Lunsumio. Talk to your healthcare provider for more information about the benefits and risks of Lunsumio.
You may report side effects to the FDA at (800) FDA-1088 or View Source You may also report side effects to Genentech at (888) 835-2555.
Please see Important Safety Information, including Serious Side Effects, as well as the Lunsumio full Prescribing Information and Medication Guide or visit View Source
About Polivy (polatuzumab vedotin-piiq)
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’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL.
Polivy U.S. Indication
Polivy is a prescription medicine used with other medicines (a rituximab product, cyclophosphamide, doxorubicin, and prednisone) as a first treatment for adults who have moderate to high risk diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL).
Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat DLBCL in adults who have progressed after at least 2 prior therapies.
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. Your doctor may stop or adjust your treatment if any serious side effects occur. Be sure to contact your healthcare team if there are any signs of these side effects.
Nerve problems in your arms and legs: This may happen as early as after your first dose and may worsen with every dose. Your doctor will monitor for signs and symptoms, such as changes in your sense of touch, numbness or tingling in your hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to your walking pattern
Infusion-related reactions: You may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of your infusion
Low blood cell counts: Treatment with Polivy can cause severe low blood cell counts. Your doctor will monitor your blood counts throughout treatment with Polivy
Infections: If you have a fever of 100.4°F (38°C) or higher, chills, cough, or pain during urination, contact your healthcare team. Your doctor may also give you medication before giving you Polivy, which may prevent some infections
Rare and serious brain infections: Your doctor will monitor closely for signs and symptoms of these types of infections. Contact your doctor if you 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 your skin or the white part of your eyes. You may be at higher risk if you already had liver problems or you are taking other medication
Side effects seen most often
The most common side effects during treatment were
Nerve problems in arms and legs
Nausea
Tiredness or lack of energy
Diarrhea
Constipation
Hair loss
Redness and sores of the lining of the mouth, lips, throat, and digestive tract
Polivy may lower your red or white blood cell counts and increase uric acid levels.
Polivy may not be for everyone. Talk to your doctor if you are
Pregnant or think you are pregnant: Data have shown that Polivy may harm your unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for 2 months after the last dose
These may not be all the side effects. Talk to your healthcare provider for more information about the benefits and risks of Polivy treatment.
You may report side effects to the FDA at (800) FDA-1088 or View Source You may also report side effects to Genentech at (888) 835-2555.
Please see the full Prescribing Information and visit View Source for additional Important Safety Information.