Article Content

FDA Breakthrough Device Designation for Prostate Cancer Liquid Biopsy Test

The FDA granted Breakthrough Device Designation for miR Sentinel Prostate Test, which is a new method to analyze small non-coding RNAs (sncRNA) derived from a simple, non-invasive urine specimen from age-eligible men. Using only the expression level of these sncRNAs, a proprietary Statistical Classification Algorithm derives scores that classify patients according to the likelihood of being in the following four possible groups: no molecular evidence of prostate cancer; low-risk; intermediate-risk; or high-risk prostate cancer.

FDA; cancer research... - Click to enlarge in new windowFDA; cancer research; clinical trials. FDA; cancer research; clinical trials

Initial validation data for the miR Sentinel Prostate Test was published in the September 2020 issue of The Journal of Urology (2020; These data show that this platform can detect molecular evidence of prostate cancer with sensitivity of 94 percent and specificity of 92 percent, which translates to AUC of 0.98. When the cancer is diagnosed, the test further classifies the cancer as either low risk with sensitivity of 93 percent and specificity of 90 percent, which translates to AUC of 0.98, or critically, as high risk with sensitivity of 94 percent and specificity of 96 percent, which translates to AUC of 0.99. The publication highlights test results based on urinary exosomes that are isolated from a single specimen of regularly passed urine. Hundreds of specifically extracted sncRNAs are then interrogated in a high-throughput real-time PCR-based platform and analyzed with a proprietary classification algorithm.


In comparison to currently available technologies alone, the specificity, sensitivity, and empirical NPV and PPV of the miR Sentinel Prostate Test may significantly reduce mortality and decrease the number of hospitalizations, physician visits, and reduce recovery time. The test was designed to revolutionize a patient's disease journey when used by a provider in conjunction with other clinical findings and/or laboratory tests.


IMGN632 in R/R Blastic Plasmacytoid Dendritic Cell Neoplasm

The FDA has granted Breakthrough Therapy designation for IMGN632 for the treatment of patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN). It was granted based on the findings from the BPDCN cohort of the first-in-human study of IMGN632, for which initial data were presented in an oral session at the American Society of Hematology (ASH) Annual Meeting in 2019.


IMGN632 is a CD123-targeting antibody-drug conjugate (ADC) in clinical development for hematological malignancies, including BPDCN, acute myeloid leukemia (AML), and acute lymphocytic leukemia (ALL). This ADC is currently being evaluated in multiple cohorts, including monotherapy for patients with BPDCN and minimal residual disease positive (MRD+) AML following frontline induction therapy and in combinations with azacitidine and venetoclax for patients with relapsed/refractory AML. IMGN632 uses a novel indolinobenzodiazepine (IGN) payload, which alkylate DNA without crosslinking. IGNs have been designed to have high potency against AML blasts, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads.


Nivolumab + Ipilimumab Approved for Unresectable Malignant Pleural Mesothelioma

Nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks (injections for intravenous use) was approved by the FDA for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma. This approval is based on a pre-specified interim analysis from the Phase III CheckMate-743 trial in which nivolumab + ipilimumab (n=303) demonstrated superior overall survival (OS) versus the platinum-based standard-of-care chemotherapy (n=302) (HR: 0.74 [95% CI: 0.61-0.89]; P=0.002), with a median OS of 18.1 months (95% CI: 16.8-21.5) versus 14.1 months (95% CI: 12.5-16.2), respectively. These results were observed after 22.1 months of minimum follow-up. At 2 years, 41 percent of patients treated with nivolumab + ipilimumab were alive and 27 percent with chemotherapy.


"Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the 5-year survival rate is approximately 10 percent," said study investigator Anne S. Tsao, MD, Professor and Section Chief of the Department of Thoracic/Head and Neck Medical Oncology, as well as Director of the Mesothelioma Program at The University of Texas MD Anderson Cancer Center.


"The survival results from the CheckMate-743 trial show that the combination of nivolumab and ipilimumab could become a new frontline standard of care option. This is exciting news, instilling hope for patients with this devastating disease and for the health care providers who care for them," she noted.


Nivolumab and ipilimumab are associated with warnings and precautions, including immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, and other adverse reactions; infusion reactions; complications of allogeneic stem cell transplant; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when nivolumab is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.


Ipilimumab is associated with the following warnings and precautions: severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplant after ipilimumab, embryo-fetal toxicity, and risks associated when administered in combination with nivolumab.


This is the third indication for a nivolumab + ipilimumab-based combination in the first-line treatment of a form of thoracic cancer. Nivolumab + ipilimumab is approved by the FDA as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 >= 1 percent as determined by an FDA-approved test, and without EGFR or ALK genomic tumor aberrations. It is also approved in combination with limited chemotherapy for the first-line treatment of adult patients with metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations regardless of PD-L1 expression.


Nivolumab + ipilimumab is a unique combination of two immune checkpoint inhibitors that features a potentially synergistic mechanism of action, targeting two different checkpoints (PD-1 and CTLA-4) to help destroy tumor cells. Ipilimumab helps activate and proliferate T cells, while nivolumab helps existing T cells discover the tumor. Some of the T cells stimulated by ipilimumab can become memory T cells, which may allow for a long-term immune response. Targeting of normal cells can also occur and result in immune-mediated adverse reactions, which can be severe and potentially fatal.


This approval was granted less than 6 weeks following the submission of a new supplemental Biologics License Application, which was reviewed under the FDA's Real-Time Oncology Review pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.


Treatment was permanently discontinued for adverse reactions in 23 percent of patients treated with nivolumab + ipilimumab, and 52 percent had at least one dose withheld for an adverse reaction. An additional 4.7 percent of patients permanently discontinued ipilimumab alone due to adverse reactions.


Serious adverse reactions occurred in 54 percent of patients receiving nivolumab + ipilimumab. The most frequent (>=2%) serious adverse reactions in patients receiving nivolumab + ipilimumab were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in four (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. The most common (>=20%) adverse reactions were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). The median number of doses was 12 for nivolumab and 4 for ipilimumab.