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Accelerated Approval of Tepotinib for Metastatic Non-Small Cell Lung Cancer

The FDA granted accelerated approval to tepotinib for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

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Efficacy was demonstrated in the VISION trial (NCT02864992), a multicenter, non-randomized, open-label, multicohort study enrolling 152 patients with advanced or metastatic NSCLC with MET exon 14 skipping alterations. Patients received tepotinib 450 mg orally once daily until disease progression or unacceptable toxicity.


The main efficacy outcome measures were overall response rate (ORR) determined by a blinded independent review committee using RECIST 1.1 and response duration. Among the 69 treatment-naive patients, the ORR was 43 percent (95% CI: 32%, 56%) with a median response duration of 10.8 months (95% CI: 6.9, not estimable). Among the 83 previously treated patients, the ORR was 43 percent (95% CI: 33%, 55%) with a median response duration of 11.1 months (95% CI: 9.5, 18.5).


The most common adverse reactions (>= 20% of patients) were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Tepotinib can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity. The recommended tepotinib dose is 450 mg orally once daily with food.


Uttroside-B Receives Orphan Drug Designation for Treating Liver Cancer

The FDA Office of Orphan Products Development has granted Orphan Drug Designation to Uttroside-B, a small molecule chemotherapeutic for the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer. In preclinical studies, Uttroside-B was up to 10-times more potent against HCC cells than sorafenib, the standard of care drug at the time.


As an orphan drug, Uttroside-B may benefit from a 7-year market exclusively following marketing approval, grant funding for clinical trials that contribute to marketing approval, protocol assistance, and tax credits. Preclinical testing is now underway to support an FDA Investigational New Drug application expected this year.


With very limited approved first-line pharmaceutical therapies for HCC available today, challenges include drug resistance, adverse side effects, and high costs. An estimated 700,000 people are diagnosed with HCC each year, with the global market for liver cancer drugs expected to grow to $3.9 billion by 2027.


New Treatment for Adults with Relapsed or Refractory Large B-Cell Lymphoma

The FDA approved lisocabtagene maraleucel, a cell-based gene therapy to treat adult patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment. Lisocabtagene maraleucel, a chimeric antigen receptor (CAR) T-cell therapy, is the third gene therapy approved by the FDA for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Lisocabtagene maraleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.


"Today's approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow, and lymph nodes," said Peter Marks, MD, PhD, Director of the FDA's Center for Biologics Evaluation and Research. "Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens."


Each dose of lisocabtagene maraleucel is a customized treatment created using a patient's own T cells, a type of white blood cell, to help fight the lymphoma. The patient's T cells are collected and genetically modified to include a new gene that facilitates targeting and killing of the lymphoma cells. Once the cells are modified, they are infused back into the patient.


The safety and efficacy of lisocabtagene maraleucel were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with lisocabtagene maraleucel was 54 percent.


Treatment with lisocabtagene maraleucel has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells, causing high fever, flu-like symptoms, and neurologic toxicities. Both CRS and neurological events can be life-threatening. Other side effects include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system. Side effects generally appear within the first 1-2 weeks following treatment, but some side effects may occur later.


Because of the risk of CRS and neurologic toxicities, lisocabtagene maraleucel is being approved with a risk evaluation and mitigation strategy (REMS) which includes elements to assure safe use (ETASU). The FDA is requiring, among other things, that health care facilities that dispense lisocabtagene maraleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of lisocabtagene maraleucel are required to be trained to recognize and manage the risks of CRS and neurologic toxicities. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion-and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with lisocabtagene maraleucel.


To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with lisocabtagene maraleucel.


Lisocabtagene maraleucel is the first regenerative medicine therapy with RMAT designation to be licensed by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. The lisocabtagene maraleucel application was reviewed using a coordinated, cross-agency approach, including both the Center for Biologics Evaluation and Research and FDA's Oncology Center of Excellence.


TH1902 Receives Fast Track Designation for Sortilin-Expressing Cancers

The FDA has granted Fast Track designation to TH1902 as a single agent for the treatment of patients with sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy.


The proposed Phase I TH1902 clinical trial design includes a dose-escalation study to evaluate the safety, pharmacokinetics, maximum tolerated dose (MTD), and preliminary anti-tumor activity of TH1902 administered once every 3 weeks in patients with advanced solid tumors refractory to available anti-cancer therapies. Once the MTD is determined, it is planned that a total of 40 additional patients will be enrolled to evaluate the potential anti-tumor activity of TH1902 in patients with endometrial, ovarian, colorectal, pancreatic, and triple-negative breast cancers where it has been estimated that the sortilin receptor is expressed in 40-90 percent of cases. The Phase I trial is expected to be initiated in the second quarter of calendar year 2021 and is designed to identify a recommended dose for Phase II development.


Funda Meric-Bernstam, MD, Chair of the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, is lead principal investigator of the Phase I trial for TH1902. The detailed study protocol is available at under the identifier number NCT04706962.