Over the past week, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to a bispecific antibody for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations; granted approval to a test for human papillomavirus–associated cervical cancer; gave Fast Track designation to a combination therapy for relapsed or refractory cervical cancer; and granted designations or clearances to several other systems or agents.
Breakthrough Therapy Designation for JNJ-6372 in Patients With Pretreated NSCLC With EGFR Exon 20 Insertion Mutations
The FDA granted Breakthrough Therapy designation to JNJ-61186372 (JNJ-6372) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. JNJ-6372 is an EGFR-mesenchymal epithelial transition factor (MET) bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications. Currently, there are no FDA-approved targeted therapies for patients with lung cancer who have EGFR exon 20 insertion mutations.
Patients with NSCLC and EGFR exon 20 insertion mutations have a form of disease that is generally insensitive to EGFR tyrosine kinase inhibitor treatments and carries a worse prognosis compared to patients with more common EGFR mutations (exon 19 deletions/L858R substitution). The current standard of care for this patient population is conventional cytotoxic chemotherapy.
The designation is supported by data from a phase I, first-in-human, open-label, multicenter study. The study is evaluating the safety, pharmacokinetics, and preliminary efficacy of JNJ-6372 as monotherapy and in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor, in adult patients with advanced NSCLC. The study seeks to determine the recommended phase II dose in patients with advanced NSCLC. Enrollment into the phase II dose expansion cohorts is ongoing, as the study evaluates JNJ-6372 monotherapy activity in multiple NSCLC subpopulations with genomic alterations, such as those with C797S resistance mutation or MET amplification.
Approval for CINtec PLUS Cytology Test in Cervical Cancer
The FDA approved the CINtec PLUS Cytology as the first biomarker-based triage test for women whose primary cervical cancer screening results are positive for the human papillomavirus (HPV) using the cobas 4800 HPV Test. The CINtec PLUS Cytology test identifies those women whose HPV infections are most likely to be associated with cervical precancers, and provides definitive information about which HPV-positive women may benefit most from immediate referral to colposcopy vs repeat testing.
In the approval, the FDA considered data from the registrational IMPACT (IMproving Primary screening And Colposcopy Triage) trial, which enrolled more than 35,000 women in the United States to clinically validate CINtec PLUS Cytology as a triage test in different screening scenarios. Publication of the study data is pending.
CINtec PLUS Cytology is expected to be widely commercially available in the United States later in 2020. The dual-stain biomarker technology included in the CINtec PLUS Cytology test detects the simultaneous presence within a single cell of the two biomarkers—p16 and Ki-67. A positive result of these two biomarkers in a single cell signals that a woman is more significantly at risk for cervical cancer.
The new test can be performed using the same liquid sample that is used for HPV or Papanicolaou cytology testing. This eliminates the need for additional or repeat sample collection or time spent waiting to find out if an infection is clearing. Primary screening by the cobas 4800 HPV DNA test with triage using the CINtec PLUS Cytology test demonstrated the high sensitivity and specificity to detect transforming HPV infections reliably and cost-effectively.
Prior to FDA approval for use in the United States, the CINtec PLUS Cytology test had been used as a triage test for HPV-positive results and mildly abnormal Pap cytology results in Europe, Asia, South America, and Australia.
Fast Track Designation for Balstilimab/Zalifrelimab in Advanced Cervical Cancer
The FDA granted Fast Track designation to balstilimab in combination with zalifrelimab for the treatment of patients with relapsed or refractory metastatic cervical cancer. Updated data from a preplanned interim analysis of the combination have been reported, which showed activity of balstilimab/zalifrelimab in patients with relapsed or refractory metastatic cervical cancer. The data demonstrated a 26.5% objective response rate (including four complete responses, five partial responses, and eight patients with stable disease). Responses have been durable (median not yet reached) in an all-comer, non–biomarker selected population of patients with refractory cervical cancer in whom prior platinum chemotherapy with or without bevacizumab has failed.
Priority Review for Copper Cu-64 Dotatate Injection
The FDA granted copper Cu-64 dotatate injection Priority Review. Copper Cu-64 dotatate is a positron-emission tomography (PET) diagnostic agent intended for somatostatin receptor–expressing neuroendocrine tumors.
“If approved, we expect that copper Cu-64 dotatate injection will have a significant impact on physicians, [patients with] neuroendocrine tumors, and their caregivers, as this will help alleviate the scheduling and supply challenges many geographies have experienced with other somatostatin analog PET agents,” said Ebrahim Delpassand, MD, Chief Executive Officer of RadioMedix, manufacturer of the injection.
Marketing Clearance for RefleXion Radiotherapy Technology
The FDA granted marketing clearance for stereotactic body radiotherapy (SBRT), stereotactic radiosurgery (SRS), and intensity-modulated radiotherapy (IMRT) with the RefleXion X1 machine.
The RefleXion X1 combines computed tomography (CT) imaging with a linear accelerator to reduce motion artifacts that can inhibit accurate targeting of the radiation dose to a patient’s tumor. Its design rotates up to 60 times faster than other linear accelerators and modulates dose delivery from 100 points per beam station. These combined improvements may reduce the side effects of radiotherapy by allowing radiation oncologists to better localize the tumor, reduce patient setup errors, and precisely deliver dose to complex tumor targets while avoiding nearby normal structures.
Biology-guided radiotherapy, a novel treatment modality under development, uses the biologic signature of a tumor to characterize its movement and to deliver a precisely tracked therapeutic radiation dose to the tumor. The RefleXion X1 machine with biology-guided radiotherapy is designed to overcome the technical limitations that currently restrict radiotherapy to one or two tumors.
Transpara 3D Cleared by FDA for Clinical Use
The FDA cleared Transpara 1.6.0, the first breast artificial intelligence solution for both two-dimensional (2D) and three-dimensional (3D) mammography in the United States.
In order to obtain FDA clearance, the company performed a clinical reader study which demonstrated that accuracy of radiologists significantly improved when reading 3D mammograms with support from Transpara. In addition, 3D reading time was significantly reduced to about 35 seconds per exam, bringing it close to 2D reading efficiency.
