FDA Approves Opdivo for Urothelial Carcinoma Indication

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FDA approved the nivolumab (Opdivo) injection for intravenous use for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

This indication was approved based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The recommended dose for mUC is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.

The FDA granted the application priority review and previously granted Breakthrough Therapy Designation to Opdivo for the treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

“Most people don’t know how common bladder cancer is and that it is the fifth most-diagnosed cancer. That’s why we are dedicated to raising awareness and supporting research efforts that may offer more treatment options to patients who need them,” said Stephanie Chisolm, director of education and research at Bladder Cancer Advocacy Network. “This approval is another exciting step forward for the bladder cancer community and provides needed hope to patients and their families.”

In the CheckMate -275 trial, 19.6% (95% CI: 15.1-24.9; 53/270) of patients responded to treatment with Opdivo. The percentage of patients with a complete response was 2.6% (7/270) and the percentage of patients with a partial response was 17% (46/270). Among responders, the median duration of response was 10.3 months (range: 1.9+-12.0+ months). The median time to response was 1.9 months (range: 1.6-7.2). CheckMate -275 is a phase II, open-label, single-arm, multicenter study evaluating Opdivo in patients with locally advanced or mUC who have disease progression during or following treatment with a platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In this study, 270 patients received Opdivo 3 mg/kg administered intravenously every two weeks until disease progression or unacceptable toxicity. The recommended dose is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate as defined by an independent radiographic review committee.


FDA Approves First Drug for Marginal Zone Lymphoma

FDA approved the drug Imbruvica (imbrutinib) for the treatment of patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least one prior anti-CD20-based therapy.

Imbruvica is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech Inc.

Imbruvica is the first therapy specifically indicated for use in patients with relapsed/refractory MZL. This approval marks the fifth unique indication for Imbruvica in the U.S.

MZL accounts for approximately 12 percent of all cases of non-Hodgkin’s lymphoma in adults.

“This milestone marks the fifth patient population for whom Imbruvica is now approved and broadens the number of patients who may be treated with the medication,” said Darrin Beaupre, head of Early Development and Immunotherapy at Pharmacyclics LLC. “We continue to research Imbruvica across many disease areas, including, but not limited to, other B-cell malignancies.”

The approval in MZL is based on data from the phase II, open-label, multi-center, single-arm PCYC-1121 study, which evaluated the safety and efficacy of Imbruvica in MZL patients who require systemic therapy and have received at least one prior anti-CD20-based therapy.

The efficacy analysis included 63 patients with three sub-types of MZL: mucosa-associated lymphoid tissue (MALT; N=32), nodal (N=17) and splenic (N=14). The ORR was achieved in nearly half (46%) of the patients (95% CI: 33.4-59.1) as assessed by an Independent Review Committee using criteria adopted from the International Working Group criteria for malignant lymphoma, with efficacy observed across all three MZL sub-types. The median time to response was 4.5 months (range, 2.3-16.4 months).

In the trial, 3.2% of patients had a complete response and 42.9% of patients had a partial response. The median duration of responses was not reached (range 16.7 months to NR). The data were previously presented at the American Society of Hematology annual meeting.

Overall, the safety data from this study was consistent with the known safety profile of Imbruvica in B-cell malignancies. The most common adverse events of all grades (occurring in ≥20% of MZL patients treated with Imbruvica included thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema and arthralgia (24% each), neutropenia and cough (22% each), and dyspnea and upper respiratory tract infection (21% each). The most common (>10%) Grade 3 or 4 AEs were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).

The risks associated with Imbruvica as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome and embryo fetal toxicities.

Imbruvica is approved to treat patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy, as well as patients with other non-Hodgkin’s lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma, including patients with 17p deletion; patients with mantle cell lymphoma who have received at least one prior therapy; and patients with Waldenström’s macroglobulinemia.

Continued approval for the MZL and MCL indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Accelerated approval was granted for this indication based on overall response rate. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.


EU Orphan Drug Designation for TB-403 for Medulloblastoma

ONCURIOUS NV, an emerging oncology company focused on the development of innovative orphan drugs for the treatment of pediatric tumors, announced that the European Commission has confirmed the orphan drug designation for TB-403 for medulloblastoma.

The EC’s decision follows the earlier positive opinion issued by the European Medicine Agency. TB-403 is a humanized monoclonal antibody against placental growth factor. PlGF is expressed in several types of cancer, including medulloblastoma.

In medulloblastoma patients, high expression of the PlGF receptor neuropilin 1 has been shown to correlate with poor overall patient survival. An orphan drug designation is for “medicines to be developed for the diagnosis, prevention or treatment of rare diseases that are life-threatening or very serious.”

The confirmation by the EC follows an earlier in-depth review and positive opinion on the drug candidate by the EMA Committee for Orphan Medicinal Products.

The COMP gathers a group of experts chosen on the strength of their qualifications and a number of patient organization representatives.

Altogether, the COMP assesses the potential incremental benefits of a drug candidate versus existing treatments. TB-403 is currently being evaluated in a phase I/IIa clinical trial for treatment of medulloblastoma, a rare and life-threatening pediatric cancer.

The clinical trial is being conducted in partnership with the Neuroblastoma and Medulloblastoma Translational Research Consortium.

The consortium is a collaboration of 25 U.S. academic medical centers, teaching hospitals and other entities, with the purpose of facilitating and conducting collaborative research activities and investigations of new treatments for neuroblastoma, medulloblastoma and other pediatric cancers.

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