FDA expands early breast cancer indication for abemaciclib with endocrine therapy

On March 3, 2023, the Food and Drug Administration (FDA) approved abemaciclib (Verzenio, Eli Lilly and Company) with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.

Patients defined as high risk included those having either ≥4 pALN (pathologic axillary lymph nodes) or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm.

Abemaciclib was previously approved for the above high-risk population with the additional requirement of having a Ki-67 score ≥20%. Today’s approval removes the Ki-67 testing requirement.

View full prescribing information for Verzenio.

Efficacy was evaluated in monarchE (NCT03155997), a randomized (1:1), open-label, two-cohort multicenter trial including adult women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of recurrence. To be enrolled in cohort 1, patients must have either ≥4 pALN or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm. To be enrolled in cohort 2, patients could not be eligible for cohort 1 and must have had 1-3 pALN and tumor Ki-67 score ≥20%. Patients were randomized to either 2 years of abemaciclib plus physician’s choice of standard endocrine therapy (tamoxifen or an aromatase inhibitor) or standard endocrine therapy alone.

The major efficacy outcome measure was invasive disease-free survival (IDFS). A statistically significant difference was observed in the intent-to-treat (ITT) population, primarily attributed to the patients in cohort 1 (cohort 1 N=5120 [91%]; IDFS HR 0.653 (95% CI: 0.567, 0.753)). IDFS at 48 months was 85.5% (95% CI: 83.8, 87.0) for abemaciclib plus standard endocrine therapy and 78.6% (95% CI: 76.7, 80.4) for standard endocrine therapy alone. Overall survival data remains immature, however, in cohort 2, more deaths were observed with abemaciclib plus standard endocrine therapy compared to standard endocrine therapy alone (10/253 vs. 5/264). Therefore, the indication was restricted to cohort 1.

The most common adverse reactions (≥20%) were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.

The recommended abemaciclib starting dose is 150 mg taken twice daily with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.

This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA Grants Accelerated Approval to Genentech’s Lunsumio, a First-in-Class Bispecific Antibody, to Treat People With R/R Follicular Lymphoma

With Lunsumio, people with heavily pretreated follicular lymphoma (FL) may experience remission with a chemotherapy-free, fixed-duration treatment that can be accessed in an outpatient settingResults from the pivotal Phase II GO29781 study demonstrated that 80% of patients who received at least two prior therapies achieved durable response rates, with 60% experiencing complete remissionDiscovered and developed by Genentech scientists, Lunsumio is now the first CD20xCD3 T-cell engaging bispecific antibody approved by the FDA to treat the most common slow-growing form of non-Hodgkin’s lymphoma, FL

South San Francisco, CA -- December 22, 2022 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Lunsumio® (mosunetuzumab-axgb) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Lunsumio, a CD20xCD3 T-cell engaging bispecific antibody, represents a new class of fixed-duration cancer immunotherapy, which is off-the-shelf and readily available, so that patients do not have to wait to start treatment. Lunsumio will be available in the United States in the coming weeks. 

“This approval is a significant milestone for people with relapsed or refractory follicular lymphoma, who have had limited treatment options until now,” said Elizabeth Budde, M.D., Ph.D., hematologic oncologist and associate professor, City of Hope Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, and Lunsumio clinical trial investigator. “As a first-in-class T-cell engaging bispecific antibody that can be initiated in an outpatient setting, Lunsumio’s high response rates and fixed-duration could change the way advanced follicular lymphoma is treated.”

“Despite treatment advances, follicular lymphoma remains incurable and relapse is common, with outcomes worsening following each consecutive treatment,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Lunsumio represents our first approved T-cell engaging bispecific antibody and builds on our legacy of more than 20 years of innovation in blood cancer.”

The FDA approval is based on positive results from the Phase II GO29781 study of Lunsumio in people with heavily pretreated FL, including those who were at high risk of disease progression or whose disease was refractory to prior therapies. Results from the study showed high and durable response rates. An objective response was seen in 80% (72/90 [95% confidence interval (CI): 70-88]) of patients treated with Lunsumio, with a majority maintaining responses for at least 18 months (57% [95% CI: 44-70]). The objective response rate is the combination of complete response (CR) rate (a disappearance of all signs and symptoms of cancer) and partial response rate (a decrease in the amount of cancer in the body). The median duration of response among those who responded was almost 2 years (22.8 months [95% CI: 10-not reached]). A CR was achieved in 60% of patients (54/90 [95% CI: 49-70]). Among 218 patients with hematologic malignancies who received Lunsumio at the recommended dose, the most common adverse event (AE) was cytokine release syndrome (CRS; 39%), which can be severe and life-threatening. The median duration of CRS events was 3 days (range: 1-29). Other common AEs (≥20%) included fatigue, rash, pyrexia and headache.

Lunsumio is administered as an intravenous infusion for a fixed-duration, which allows for time off therapy, and can be infused in an outpatient setting. Hospitalization may be needed to manage select AEs, should be considered for subsequent infusions following a Grade 2 CRS event, and is recommended for subsequent infusions following a Grade 3 CRS event.

“This additional treatment option is good news for people whose blood cancer has not responded to multiple lines of treatment because it can become more difficult to treat each time it returns,” said Dr. Lee Greenberger, chief scientific officer of the Leukemia & Lymphoma Society. “This bispecific antibody is an off-the-shelf, accessible treatment option that has the potential to help those with relapsed or refractory follicular lymphoma achieve remission.”

Lunsumio was developed based on Genentech’s broad expertise in creating bispecific antibodies. Lunsumio is designed to address the diverse needs of people with blood cancer, physicians and practice settings, and is part of the company’s robust bispecific antibody clinical program in lymphoma. Lunsumio is being further investigated as a subcutaneous formulation (i.e., administered under the skin) and in Phase III studies that will expand the understanding of its impact in earlier lines of treatment in people with non-Hodgkin’s lymphoma.

Genentech is committed to helping people access the medicines they are prescribed and will be offering comprehensive services for people prescribed Lunsumio to help minimize barriers to access and reimbursement. For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is also available at 866-4ACCESS/866-422-2377 or www.Genentech-Access.com. 

About the GO29781 Study
 The GO29781 study [NCT02500407] is a Phase II, multicenter, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of Lunsumio® (mosunetuzumab-axgb) 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, safety and tolerability (secondary endpoints).

About Follicular Lymphoma
 Follicular lymphoma (FL) is the most common slow-growing (indolent) form of non-Hodgkin’s lymphoma, accounting for about one in five cases. It typically responds well to treatment but is often characterized by periods of remission and relapse. The disease typically becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis. It is estimated that, in the United States, approximately 13,000 new cases of FL will be diagnosed in 2022 and more than 100,000 people are diagnosed with FL each year worldwide.

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. 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

• 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

• cough

•  chest pain

• tiredness

• shortness of breath

• painful rash

• sore throat

• pain during urination

• feeling weak or generally unwell

• Low blood cell counts. Low blood cell counts are common during treatment with LUNSUMIO and can also be severe. Your healthcare provider will check your blood cell counts during treatment with LUNSUMIO. LUNSUMIO may 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 may 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: tender or swollen lymph nodes, chest pain, cough, trouble breathing, and 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 lab 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 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 health care 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 health care provider for more information about the benefits and risks of LUNSUMIO.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. 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.

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 http://www.gene.com/hematology.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

FDA approves first GTx for the Treatment of High-Risk, Non-Muscle-Invasive Bladder Cancer

Today, the U.S. Food and Drug Administration approved Adstiladrin (nadofaragene firadenovec-vncg), a non-replicating (cannot multiply in human cells) adenoviral vector based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

“This approval provides healthcare professionals with an innovative treatment option for patients with high-risk non-muscle invasive bladder cancer that is unresponsive to BCG therapy,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Today’s action addresses an area of critical need. The FDA remains committed to facilitating the development and approval of safe and effective cancer treatments.”

Bladder cancer, one of the more common forms of cancer, is a disease in which malignant (cancer) cells form a tumor in the tissues of the bladder. These abnormal cells can invade and destroy normal body tissue. Over time, the abnormal cells can also metastasize (spread) through the body. Most newly diagnosed bladder cancers (75% to 80%) are classified as NMIBC – a type of cancer that has grown through the lining of the bladder but hasn’t yet invaded the muscle layer. This type of cancer is associated with high rates of recurrence (between 30 to 80%) and the risk of progression to invasive and metastatic cancer.  

Treatment and care of patients with high-risk NMIBC, including those with carcinoma in situ, or CIS (abnormal cancer cells found in the place where they first formed and that have not spread to nearby tissue), often involves removing the tumor and the use of BCG to reduce the risk that the cancer will recur. Few effective treatment options exist for patients who develop BCG-unresponsive disease. The failure to achieve a complete response, or the disappearance of all signs of cancer as seen on cystoscopy, biopsied tissue, and urine, is associated with an increased risk of death or a disease-worsening event. Without treatment, the cancer can invade, damage tissues and organs, and spread through the body. According to the Centers for Disease Control and Prevention, about 57,000 men and 18,000 women are diagnosed with bladder cancer annually, and roughly 12,000 men and 4,700 women die from the disease each year in the United States.

The safety and effectiveness of Adstiladrin was evaluated in a multicenter clinical study that included 157 patients with high-risk BCG-unresponsive NMIBC, 98 of whom had BCG-unresponsive CIS with or without papillary tumors and could be evaluated for response. Patients received Adstiladrin once every three months for up to 12 months, or until unacceptable toxicity to therapy or recurrent high-grade NMIBC. Overall, 51% of enrolled patients using Adstiladrin therapy achieved a complete response (the disappearance of all signs of cancer as seen on cystoscopy, biopsied tissue, and urine). The median duration of response was 9.7 months. Forty-six percent of responding patients remained in complete response for at least one year.

Adstiladrin is administered once every three months into the bladder via a urinary catheter. The most common adverse reactions associated with Adstiladrin included bladder discharge, fatigue, bladder spasm, urinary urgency, hematuria (presence of blood in urine), chills, fever, and painful urination. Individuals who are immunosuppressed, or immune-deficient should not come into contact with Adstiladrin. 

This application was granted Priority Review, Breakthrough Therapy, and Fast Track designations.

The FDA granted approval of Adstiladrin to Ferring Pharmaceuticals A/S.

FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC

On December 12, 2022, the Food and Drug Administration (FDA) granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics, Inc.), a RAS GTPase family inhibitor, for adult patients with KRAS G12C¬-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

FDA also approved the QIAGEN therascreen KRAS RGQ PCR kit (tissue) and the Agilent Resolution ctDx FIRST Assay (plasma) as companion diagnostics for Krazati. If no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Approval was based on KRYSTAL-1, a multicenter, single-arm, open-label clinical trial (NCT03785249) which included patients with locally advanced or metastatic NSCLC with KRAS G12C mutations. Efficacy was evaluated in 112 patients whose disease has progressed on or after platinum-based chemotherapy and an immune checkpoint inhibitor, given either concurrently or sequentially. Patients received adagrasib 600 mg orally twice daily until disease progression or unacceptable toxicity.

The main efficacy outcome measures were confirmed objective response rate (ORR) according to RECIST 1.1, as evaluated by blinded independent central review, and duration of response (DOR). The ORR was 43% (95% CI: 34%, 53%) and median DOR was 8.5 months (95% CI: 6.2, 13.8).

The most common adverse reactions (≥ 20%) were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium.

The recommended adagrasib tablet dose is 600 mg orally twice daily until disease progression or unacceptable toxicity.

View full prescribing information for Krazati.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted fast-track, breakthrough therapy, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approves atezolizumab for alveolar soft part sarcoma

On December 9, 2022, the Food and Drug Administration (FDA) approved atezolizumab (Tecentriq, Genentech, Inc.) for adult and pediatric patients 2 years of age and older with unresectable or metastatic alveolar soft part sarcoma (ASPS).

Efficacy was evaluated in Study ML39345 (NCT03141684), an open-label, single-arm study in 49 adult and pediatric patients with unresectable or metastatic ASPS. Eligible patients were required to have histologically or cytologically confirmed ASPS incurable by surgery and an ECOG performance status of ≤2. Patients were excluded for primary central nervous system (CNS) malignancy or symptomatic CNS metastases, clinically significant liver disease, or a history of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or active pneumonitis on imaging. Adult patients received 1200 mg intravenously and pediatric patients received 15 mg/kg (up to a maximum of 1200 mg) intravenously once every 21 days until disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) determined by an independent review committee using RECIST v1.1. ORR was 24% (95% CI: 13, 39). Of the 12 patients who experienced an objective response, 67% had a DOR of 6 months or more, and 42% had a DOR of 12 months or more.

The median patient age was 31 years (range: 12-70); 47 adult patients (2% were ≥65 years of age) and 2 pediatric patients ≥12 years of age were enrolled; 51% were female, 55% White, 29% Black or African American, 10% Asian.

The most common adverse reactions (≥15%) were musculoskeletal pain (67%); fatigue (55%); rash (47%); cough (45%); nausea, headache, and hypertension (43% each), vomiting (37%), constipation and dyspnea (33% each), dizziness and hemorrhage (29% each), insomnia and diarrhea (27% each), pyrexia, anxiety, abdominal pain and hypothyroidism (25% each), decreased appetite and arrhythmia (22% each), influenza-like illness and weight decreased (18% each), and allergic rhinitis and weight increased (16% each).

The recommended atezolizumab dosage for adult patients is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks until disease progression or unacceptable toxicity. The recommended dosage for pediatric patients 2 years of age and older is 15 mg/kg (up to a maximum of 1200 mg) every 3 weeks until disease progression or unacceptable toxicity.

View full prescribing information for Tecentriq.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 3 weeks ahead of the FDA goal date.

This application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov

FDA approves olutasidenib for r/r AML with a susceptible IDH1 mutation

FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer

On November 14, 2022, the Food and Drug Administration granted accelerated approval to mirvetuximab soravtansine-gynx (Elahere, ImmunoGen, Inc.) for adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Mirvetuximab soravtansine-gynx is a folate receptor alpha directed antibody and microtubule inhibitor conjugate. Patients are selected for therapy based on an FDA-approved test.

Today, the FDA also approved the VENTANA FOLR1 (FOLR-2.1) RxDx Assay (Ventana Medical Systems, Inc.) as a companion diagnostic device to select patients for the above indication.

Efficacy was evaluated in Study 0417 (NCT04296890), a single-arm trial of 106 patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients were permitted to receive up to three prior lines of systemic therapy. All patients were required to have received bevacizumab. The trial enrolled patients whose tumors were positive for FRα expression as determined by the above assay. Patients were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, Grade >1 peripheral neuropathy, or noninfectious interstitial lung disease.

Patients received mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every three weeks until disease progression or unacceptable toxicity. Tumor response assessments occurred every six weeks for the first 36 weeks and every 12 weeks thereafter.

The main efficacy outcome measures were investigator-assessed overall response rate (ORR) and duration of response (DOR) evaluated according to RECIST version 1.1. In the efficacy evaluable population of patients who had platinum resistant, measurable disease, and received at least one dose (104 patients), the confirmed ORR was 31.7% (95% CI: 22.9, 41.6) and median DOR was 6.9 months (95% CI: 5.6, 9.7).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin. Product labeling includes a boxed warning for ocular toxicity.

The recommended mirvetuximab soravtansine-gynx dose is 6 mg/kg adjusted ideal body weight (AIBW) administered once every three weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity.

View full prescribing information for Elahere.

This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approves Seagen's Adcetris in combination with chemotherapy for pediatric patients with classical Hodgkin lymphoma

On November 10, 2022, the Food and Drug Administration approved brentuximab vedotin (Adcetris, Seagen, Inc.) in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for pediatric patients 2 years of age and older with previously untreated high risk classical Hodgkin lymphoma (cHL). This is the first pediatric approval for brentuximab vedotin.

Efficacy was evaluated in a randomized, open-label, actively controlled trial. High risk was identified as Ann Arbor Stage IIB with bulk disease, Stage IIIB, Stage IVA, and Stage IVB. Of the 600 total patients randomized, 300 were randomized to brentuximab vedotin plus doxorubicin (A), vincristine (V), etoposide (E), prednisone (P), and cyclophosphamide (C) [brentuximab vedotin + AVEPC], and 300 patients were randomized to A+bleomycin (B)+V+E+P+C [ABVE-PC] arm. Patients in each treatment arm received up to 5 cycles of the following:

• Brentuximab vedotin + AVEPC arm: brentuximab vedotin 1.8 mg/kg over 30 minutes (day 1), doxorubicin 25 mg/m2 (days 1 and 2), vincristine 1.4 mg/m2 (day 8), etoposide 125 mg/m2(days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2); or

• ABVE-PC arm: doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day1) and 10 units/m2 (day 8), vincristine 1.4 mg/m2 (days 1 and 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2).

The main efficacy outcome measure was event-free survival (EFS), defined as the time from randomization to the earliest of disease progression or relapse, second malignancy, or death due to any cause. Median EFS was not reached in either arm. There were 23 events (8%) in the brentuximab vedotin + AVEPC arm and 52 events (17%) in the ABVE-PC arm with a corresponding hazard ratio of 0.41 (95% CI: 0.25, 0.67; p=0.0002).

The most common Grade ≥3 adverse reactions (≥5%) in pediatric patients treated with brentuximab vedotin in combination with AVEPC were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.

The recommended brentuximab vedotin dose for pediatric patients 2 years of age and older is 1.8 mg/kg up to a maximum of 180 mg in combination with AVEPC every 3 weeks for a maximum of 5 doses.

View full prescribing information for Adcetris.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Brentuximab vedotin has orphan drug designation for the treatment of Hodgkin lymphoma.