Jennifer Gershman, PharmD, CPh

home

authors

jennifer-gershman-pharmd-cph

 (nivolumab) is a programmed death receptor-1 (PD-1) blocking antibody that has been approved by the FDA approved for the treatment of a variety of cancers, including patients with locally advanced or metastatic urothelial carcinoma that meet the following criteria: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.

 for Opdivo for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection, regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status.

Adjuvant therapy is follow-up treatment after the initial treatment. Tecentriq (atezolizumab) and Keytruda (pembrolizumab)

The FDA’s go-ahead was based on the phase III 

 study, which was a multicenter, double-blind, randomized, controlled trial that examined the role of adjuvant treatment with Opdivo therapy in high-risk, muscle-invasive urothelial carcinoma after radical surgery.There were 353 patients assigned to receive Opdivo 240 mg intravenously and 356 to receive placebo every two weeks for up to one year.Additionally, the primary endpoints of the study were disease-free survival among all the patients in the intention-to-treat (ITT) population and among study participants with a tumor programmed death ligand 1 (PD-L1) expression level of 

 1%.An ITT population means that all the results of the patients randomized were included in the analysis, which is more reflective of what occurs in clinical practice.The secondary end point was survival free from recurrence outside the urothelial tract.

The median disease-free survival in the ITT population was 20.8 months with Opdivo and 10.8 months with placebo. The proportion of patients who were alive and disease-free at six months was 74.9% with Opdivo and 60.3% with placebo. Among patients with a PD-L1 expression of 

 1%, the percentage of patients alive in the Opdivo group was 74.5% and 55.7% in the placebo group. The percentage of patients who were alive and free from recurrence outside the urothelial tract at six months was 77% with Opdivo compared with 62.7% in the placebo group. Treatment-related adverse events of grade 3 (severe) or higher occurred in 17.9% of the Opdivo group patients and 7.2% of the placebo group study participants.

Articles

Tecentriq and Keytruda may also be eventually approved as adjuvant therapies.

Opdivo Gets FDA Nod as Adjuvant Therapy for Muscle-Invasive Urothelial Cancer

 is a late-stage clinical company developing promising targeted fusion protein therapeutics for the treatment of cancer. But the company got bad news recently when it received a complete response letter — a form of rejection — from FDA for Vicineum (oportuzumab monatox-qqrs) for the treatment of patients with non-muscle invasive bladder cancer that hasn’t responded to a common treatment.

“We are deeply disappointed by this unexpected result, and it is an unfortunate day for patients suffering from BCG-unresponsive NMIBC.We remain dedicated to our mission to save and improve the lives of patients by bringing new treatment options to patients, and we intend to work closely with the FDA to understand next steps,” said 

, D.V.M., president, and chief executive officer of Sesen Bio.

BCG stands for bacillus Calmette-Guerin, a live weakened strain of the 

 Infusing BCG directly into the bladder is one treatment option for bladder cancer. It is often used after the cancer has come back. Why BCG works to combat cancer isn’t fully understood but it may coax the immune system into action in a way that mounts an immunological response to the cancer..

The FDA outlined specific recommendations for additional clinical/statistical data and analyses of Vicineum, in addition to chemistry, manufacturing, and controls issues regarding a recent preapproval inspection and product quality.

The company plans to request a Type A meeting with the FDA to discuss the future steps required before the BLA can be approved. 

 meetings with the FDA may include the following:

Post-action meetings requested by the sponsor within 3 months after an FDA regulatory action other than an approval

Vicineum targets epithelial cell adhesion molecule antigens (EpCAM) on the surface of tumor cells, and this innovative technology is expected to decrease the risk of toxicity to health tissues to improve drug safety. Additionally, EpCAM has been shown to be overexpressed in non-muscle invasive bladder cancer.

The FDA accepted the Sesen Bio’s application for Vicineum in February 2021, and the application was granted priority review.

Non-muscle invasive bladder cancer is, as the name suggests, bladder cancer that occurs in the surface of the bladder cancer (the inside surface), not the muscle tissue of the organ.

Developers of the drug express disappointment but plan to seek meetings with regulators in hopes of reviving the application.

FDA Denies Vicineum Approval for Non-Muscle Invasive Bladder Cancer 

 (loncastuximab tesirine-lpyl) was granted accelerated approval on April 23, 2021, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. 

Approval was based on the study LOTIS-2 that showed the overall response rate was 48.3% (95% CI: 39.9, 56.7) with a complete response rate of 24.1% (95% CI: 17.4, 31.9) after a median follow-up of 7.3 months. The drug generated net sales of $3.8 million in the two months after the approval, according to ADC Therpeutics, the Swiss company that markets Zynlonta.

 (melphalan flufenamide) was approved in February 2021 for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.Under the accelerated approval, the manufacturer, Oncopeptides AB, is required to conduct the 

 announced that data from that trial was suggesting that treatment with Pepaxto led to an increased risk of death. Ongoing trials of the drug were suspended, and the FDA said it was “encouraging” healthcare professionals “to review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments.”

The FDA announcement also said that patients being treated with the drug should discuss with their health care professional the risks and benefits of receiving Pepaxto. The drug regulatordirected healthcare professionals and patients to report anyadverse events associated with Pepaxto through the 

The FDA granted accelerated approval and orphan drug designation to Ukoniq (umbralisib) in February 2021 for marginal zone lymphoma (MZL) and follicular lymphoma (FL). Approval was based on two single-arm cohorts of a multicenter multi-cohort trial, 

 showing patients with MZL had an overall response rate of 49% with 16% achieving complete responses.Additionally, patients with FL had an overall response rate of 43% with 3% achieving complete responses. Serious adverse reactions occurred in 18% of patients, with the most common being diarrhea-colitis and infection.

The confirmatory trial of one of the approved drugs, Pepaxto, was halted when data suggested it was associated with a higher mortality rate. 

3 Important Blood Cancer Drug Approvals You Should Know About

Interest and research into urothelial cancer is growing and with that, the number of medical conferences where urothelial cancer will be an important topic. The delta variant of the COVID-19 virus is wreaking havoc with conference planning. A number of groups have pulled back their plans for an in-person meeting and have gone back to a virtual format.

The American Urological Association (AUA) 2021 Annual Meeting

The AUA annual meeting will be held in-person and virtually September 10-13, 2021 from Las Vegas, Nevada, and the program will offer evidence-based medical information for urologists and other healthcare professionals in the field globally, which includes the latest research, new guidelines, and advances in the specialty. Here are some of the topics that will be presented at the conference:

Surgical updates for upper tract urothelial cancer

MD Anderson Cancer Center Multidisciplinary Collaborative Cancer Care Conference 2020

This conference was postponed in 2020 and is now scheduled to take place October 16-21, 2021 in Aspen, Colorado. Physicians and other healthcare professionals from all disciplines who treat cancer patients generally attend this conference. The conference agenda will be available soon, and the focus will include diagnosis and management options that improve health outcomes.

Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting

The SITC conference is scheduled for November 10-14, 2021 at the Walter E. Washington Convention Center in Washington D.C. and will include virtual options. Additionally, this is the largest conference to focus solely on cancer immunotherapy that brings together international leaders from academia, regulatory and government agencies, and industry representatives. Conference agenda topics and events include the following:

CAR T in solid tumors and novel combinations

COVID-19 antibody responses in cancer patients

At this time, two of three conferences have been reverted to a in-person and virtual format. This includes The American Urological Association (AUA) 2021 Annual Meeting and the Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting.

Jennifer Gershman, PharmD, CPh

Articles

Opdivo Gets FDA Nod as Adjuvant Therapy for Muscle-Invasive Urothelial Cancer

FDA Denies Vicineum Approval for Non-Muscle Invasive Bladder Cancer

3 Important Blood Cancer Drug Approvals You Should Know About

3 Upcoming Urothelial Cancer Conferences