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.

On December 09, 2024 Delta-Fly Pharma reported Following to the previous information on Oct. 28th. in 2024, we are excited to share our latest development status (Press release, Delta-Fly Pharma, DEC 9, 2024, View Source [SID1234648965]).

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We are pleased to announce that the data review committee (DMC) has approved the tolerability of the first three patients enrolled in the Phase I/II clinical trial of DFP-10917 in combination with Venetoclax (VEN) (NCT06382168) conducted at five US clinical sites for patients with acute myeloid leukemia (AML) who have failed/relapsed after standard VEN therapy (first-line therapy). Additionally, the bone marrow cell count in peripheral blood in all three cases was 0 (zero) within 4 (four) weeks of starting treatment, and complete remission (CR or CRi) was confirmed by subsequent bone marrow biopsy.

Three more patients will be added at the current dosage regimen, and after confirmation of the tolerability, the study will move to Phase II. Complete remission has been observed in patients who have failed/relapsed after existing VEN combination therapy (first-line therapy), so this is expected to be a new, highly effective second-line therapy for patients with AML.

As previously reported, the data cleaning processes for interim analysis are currently underway for Phase III comparative clinical trial (150 cases) of DFP-10917 monotherapy targeting patients with AML receiving third-line or later therapy. Once this is completed, the results will be submitted to the Independent Data Safety Monitoring Committee (DSMB) along with electrocardiogram and pharmacokinetic study results for their advice.

On December 9, 2024 Leukogene Therapeutics reported SCRA awarded the Medical University of South Carolina $870,000 (Press release, Leukogene Therapeutics, DEC 9, 2024, View Source [SID1234656559]). MUSC has $397,000 in matching funds for a total of over one million dollars to bring three innovations into the marketplace. They include a recombinant protein cancer vaccine, an antibiotic-eluting implant device, and a burn wound gel. The project will also connect MUSC investigators with companies across the state to create strategic academic-industry collaborations. The College of Charleston, Furman University, and Wofford College are working with MUSC on the projects. The industry partners are Pearl Biologics of Daniel Island, SC, Parimer Scientific (SCRA Member Company) of Easley, SC, and Leukogene Therapeutics (SCRA Member Company), based at MUSC.

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On December 9, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported additional positive data from the AUGMENT-101 trial of Revuforj (revumenib) in relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML) and the BEAT AML trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed AML patients (Press release, Syndax, DEC 9, 2024, View Source [SID1234648918]). Revuforj is the Company’s oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

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"These new data continue to highlight the exciting potential for Revuforj as both a monotherapy and in combination with other therapies," said Michael A. Metzger, Chief Executive Officer of Syndax. "The recent approval of Revuforj for R/R acute leukemia with a KMT2A translocation, coupled with the consistency of the results we have reported across KMT2Ar and mNPM1 within the different trials and populations, continues to bolster our confidence in its practice-changing and blockbuster potential."

Additional Results from R/R mNPM1 AML Patients in Pivotal Phase 2 Portion of AUGMENT-101

Syndax recently announced that the primary endpoint was met with a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23% (15/64; 95% confidence interval [CI]: 14%, 36%; one-sided p-value =0.0014) in the protocol-defined efficacy population of 64 adults with R/R mNPM1 AML in the Phase 2 cohort of the AUGMENT-101 trial of revumenib (DCO: September 2024). The median duration of CR/CRh responses was 4.7 months at the time of the data cutoff with three patients remaining in response. Minimal residual disease (MRD) status was assessed in 14 of 15 patients who achieved CR/CRh, 64% (9/14) of whom were MRD negative. The overall response rate (ORR)1 was 47% (30/64). The safety profile observed with revumenib in the 84 patients enrolled in the cohort was consistent with previously reported data.

Syndax announced today additional results from the Phase 2 cohort of R/R mNPM1 AML patients in the AUGMENT-101 trial, including data generated from the protocol-defined efficacy population of 64 adults and a post-hoc efficacy analysis based on all patients who met the efficacy evaluable criteria.

Subgroup analyses from the Phase 2 protocol-defined R/R mNPM1 efficacy population (N=64) show that CR/CRh responses were observed across all major subgroups, including patients with multiple prior lines of therapy and prior venetoclax exposure, although the trial was not powered to evaluate differences among subgroups. The CR+CRh rate was 25% (4/16) among patients with 1 prior line of therapy, 20% (5/25) among patients with 2 prior lines of therapy, and 26% (6/23) among patients who had received three or more prior lines of therapy. The CR+CRh rate was 44% (7/16) among patients without prior venetoclax exposure and 17% (8/48) among patients with prior venetoclax exposure. Historically, AML patients who have failed prior treatment with venetoclax are unlikely to respond to subsequent therapy, with a CR rate of 6% reported for other targeted therapies after prior venetoclax therapy.2

Syndax also shared results from an expanded analysis of the R/R mNPM1 AML patients who enrolled into the Phase 2 cohort of AUGMENT-101. Among the 84 patients enrolled in the cohort, 77 met the efficacy evaluable criteria requiring patients to have blast counts >5% measured within 28 days prior to treatment and a centrally confirmed NPM1 mutation. In this expanded post-hoc efficacy analysis, 48% (37/77; 95% CI: 37%, 60%) achieved an overall response, and 26% (20/77; 95% CI: 17%, 37%) achieved a CR/CRh. The median duration of CR/CRh response was 4.7 months as of the September 2024 DCO. Minimal residual disease (MRD) status was assessed in 19 of 20 patients who achieved CR/CRh, 63% (12/19) of whom were MRD negative.

Updated Data from BEAT-AML Trial of Revumenib in Combination with Venetoclax and Azacitidine in Newly Diagnosed AML Patients

Today the company announced an update from the Phase 1 BEAT-AML trial evaluating the combination of revumenib with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2A-rearranged (KMT2Ar) AML patients aged 60 years or older. The trial is being conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial. Today’s update builds on the BEAT AML data that was presented in June at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress from 24 efficacy evaluable patients showing a composite complete remission (CRc) rate of 96% (23/24) as of a May 2024 data cutoff.

As of a November 2024 data cutoff, 46 newly diagnosed mNPM1 (n=37) or KMT2Ar (n=9) patients have been enrolled in BEAT AML across two dose levels of revumenib (113 mg q12 or 163 mg q12h with azoles) in combination with venetoclax and azacitidine. The median age of patients enrolled was 71 years (range: 60-92).

The efficacy evaluable population includes 37 patients across both dose levels with an ORR1 of 100% (37/37) and CRc rate of 95% (35/37). The rate of MRD negativity was 95% (35/37). 27% (10/37) of patients proceeded to hematopoietic stem cell transplant (HSCT).

Revumenib was generally well tolerated at both the 113 mg and 163 mg q12h dose in combination with venetoclax and azacitidine. In the safety population (N=46), 15% (7/46) of patients experienced differentiation syndrome with two (4%) Grade 3 or greater events. 43% (20/46) of patients experienced QTc prolongation with five (11%) Grade 3 or greater events. DS and QTc prolongations were self-limiting and did not cause any discontinuations. Analysis of the onset and extent of hematologic toxicities suggest a similar experience to what has been reported for the venetoclax/azacitidine doublet alone. Overall, there were no new or increased safety signals observed when revumenib was included in this triplet combination.

"These are very exciting data that highlight the potential for revumenib to enhance the responses typically observed with venetoclax/azacitidine in newly diagnosed patients with mNPM1 or KMT2Ar who are unfit to receive intensive chemotherapy," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center. "These new data continue to show that revumenib has a safety profile that could enable it to be combined with venetoclax/azacitidine and, importantly, we are observing high rates of response and MRD negativity that underscore the potential for revumenib to become an integral component of frontline treatment for KMT2Ar and mNPM1 AML patients."

Enrollment in the expansion cohort is ongoing at both dose levels. The Company plans to initiate a pivotal trial with this combination in front-line newly diagnosed patients by year-end 2024.

Syndax Corporate Event

The new data described above, along with other data presented through today at the 66th ASH (Free ASH Whitepaper) Annual Meeting being held in San Diego, CA for both the Revuforj (revumenib) and Niktimvo (axatilimab-csfr) clinical programs, will be highlighted at the Company’s investor event on Monday, December 9, 2024 at 7:00 a.m. PT/10:00 a.m. ET. The live audio webcast and accompanying slides for the event may be accessed through the Events & Presentations page in the Investors section of the Company’s website or directly through the meeting link here.

For those unable to participate in the conference call or webcast for the event, a replay will be available on the Investors section of the Company’s website at www.syndax.com for a limited time.

About Revuforj (revumenib)

Revuforj (revumenib) is an oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

Revumenib is in development for the treatment of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1). Positive pivotal data from the AUGMENT-101 trial in this population with revumenib as a monotherapy were recently reported. The Company expects to file a supplemental NDA filing for revumenib in R/R mNPM1 AML in the first half of 2025. Additionally, multiple trials of revumenib in combination with standard-of-care agents in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing across the treatment landscape, including in newly diagnosed patients.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.

Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10-mg IV every 12 hours in adults or dexamethasone 0.25-mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids.

QTc interval prolongation: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec
Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Embryo-fetal toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.

ADVERSE REACTIONS
Fatal adverse reactions occurred in 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.

Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).

DRUG INTERACTIONS
Drug interactions can occur when Revuforj is concomitantly used with:

Strong CYP3A4 inhibitors: reduce Revuforj dose
Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj
QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec.
SPECIFIC POPULATIONS
Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.

Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

On December 9, 2024 Taiho Oncology, Inc., reported results of two studies focused on oral therapies for patients with myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN), at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, Dec. 7-10, 2024, in San Diego (Press release, Taiho, DEC 9, 2024, View Source [SID1234648934]).

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Findings from a Phase 1 dose escalation trial of ASTX030, an investigational combination of azacitidine and cedazuridine, were shared with attendees during an oral presentation. In addition, results of a real-world study comparing clinical outcomes with INQOVI (decitabine and cedazuridine) tablets, an oral hypomethylating agent (HMA), versus intravenous (IV) or subcutaneous (SC) decitabine and azacitidine, respectively, were shared in a poster presentation.

Azacitidine and decitabine are HMAs. Following oral administration, HMAs are rapidly degraded by cytidine deaminase, resulting in poor oral bioavailability. Cedazuridine is a cytidine deaminase inhibitor, with the potential to increase the bioavailability of HMAs.

"We’re pleased to join hematology scientific leaders at the ASH (Free ASH Whitepaper) meeting to share data on oral HMAs for patients living with complications from MDS," said Harold Keer, MD, PhD, Chief Medical Officer, Taiho Oncology. "When administered at home, HMAs such as ASTX030 and INQOVI may potentially reduce the toll of time toxicity many patients with cancer experience and may help them to manage this disease long-term as a chronic condition."

Oral Presentation: Results of Phase 1 Open-Label Dose Escalation and Expansion Trial of ASTX030 (Oral Azacitidine + Cedazuridine)

This Phase 1 trial aimed to determine the optimal dose and formulation of ASTX030 to achieve oral azacitidine area under the curve (AUC) exposures comparable to SC azacitidine.

The trial enrolled 88 patients with MDS and MDS/MPN overlap syndromes, including chronic myelomonocytic leukemia (CMML), who received a median of seven cycles of treatment with ASTX030. Six combinations of azacitidine (60–144 mg) and cedazuridine (20–100 mg) doses were evaluated in the dose escalation portion of the trial, and two ASTX030 dose combinations (136 mg of azacitidine with 20 mg of cedazuridine and 144 mg of azacitidine with 20 mg of cedazuridine) were evaluated in the dose-expansion portion.

Pharmacokinetic data showed that 20 mg of cedazuridine sufficiently prevented azacitidine from degradation during first pass in the digestive tract and liver resulting in enhanced azacitidine bioavailability, achieving AUC exposures comparable to SC azacitidine, and the dose combination of 140 mg azacitidine/20 mg cedazuridine was recommended for evaluation in Phase 2.

The clinical efficacy results were consistent with parenteral azacitidine. The median overall survival was 29.5 months, with overall response rate of 56% (11% complete response, 0% partial response, 34% marrow complete response, 10% hematologic improvement), 27% stable disease, 2% progressive disease and 15% not evaluable.

Treatment emergent adverse events (TEAEs) were reported in 100% of participants, with 86% experiencing an AE of grade 3 or higher and 9% discontinuing treatment due to an AE. The most common TEAEs of grade 3 or higher were related to myelosuppression. Gastrointestinal AEs also reflected a similar safety profile to that typically associated with SC azacitidine. There was one dose-limiting toxicity that was possibly related to the study drug — a case of prolonged grade 4 neutropenia.

"These results are promising, as they demonstrate the potential of this novel oral therapy to reduce the treatment burden for people with MDS," said Guillermo Garcia-Manero, MD, professor of Leukemia at The University of Texas MD Anderson Cancer Center and the study’s lead investigator. "We look forward to soon sharing the results of a recently completed Phase 2 study of ASTX030 and are planning a Phase 3 trial of the compound."

Real-World Use Patterns and Outcomes for MDS Patients Treated with INQOVI or IV/SC HMA

The real-world study evaluated HMAs use patterns and clinical outcomes in adults with MDS who received first-line treatment with either INQOVI or a similar HMA administered subcutaneously or intravenously. Real-world treatment outcomes among MDS patients were gathered through the ConcertAI real-world electronic health records database.

Of 2,101 enrolled patients, 405 were treated with INQOVI and 1,696 with IV or SC azacitidine or decitabine.

Patients receiving INQOVI had a numerically longer median real-world overall survival (rwOS) compared to those treated with IV/SC HMA (23.2 versus 19.0 months) and lower risk of death, although the differences were not statistically significant.

Notably, median acute myeloid leukemia (AML)-free survival was 16.5 months with INQOVI versus 13.3 months with IC/SC HMAs (p=0.009). Furthermore, in a Cox-adjusted model, patients treated with INQOVI had a 16% lower risk of AML transformation or death (HR=0.84; 95% CI: 0.73–0.98; p=0.027) compared with those treated with IV or SC HMAs.

Those who received INQOVI prolonged the time to next treatment: 9.4 months, versus 7.4 months for those in the IV/SC cohort (p<0.001). Patients who received INQOVI were 18% less likely than their study counterparts receiving IV/SC HMAs to receive a next treatment (HR=0.82; 95% CI: 0.71–0.94; p=0.004).

"This real-world study is among the first and largest to examine clinical outcomes in patients treated for MDS with either first-line INQOVI or an intravenous or subcutaneous hypomethylating agent," said Tehseen Salimi, MD, MHA, Senior Vice President and Head of Medical Affairs, Taiho Oncology. "In addition to demonstrating comparable overall survival between the two treatment options, this study identified some potentially exciting unique signals of efficacy in patients who took INQOVI. These results highlight the potential value of this compound as an alternative to parenteral hypomethylating agents."

INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

Decitabine and cedazuridine, marketed under the brand name INQOVI, is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6 months (females) or 3 months (males) after last dose.

ADVERSE REACTIONS

Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for 2 weeks after the last dose.

Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).

Please see full Prescribing Information.