Kristi Rosa

The FDA has granted 2 breakthrough device designations to cover new intended uses of the Signatera molecular residual disease (MRD) test developed by Natera, Inc., according to a recent announcement.

The new designations will support the development of the test through phase 3 clinical trials as a companion diagnostic to 2 cancer treatments. With the breakthrough device designation granted in 2019, the Signatera MRD test now has 3 designations for use across several cancer types and indications.

“We are committed to working with the FDA and with our biopharma partners to validate the use of the Signatera MRD test across a broad range of solid tumor indications,” Fayyaz Memon, vice president of Regulatory Affairs at Natera, commented in the press release. “These 2 new breakthrough device designations will help us accelerate our mission to bring life-saving diagnosis and treatment to [patients with] cancer as early as possible.”

The custom-build circulating tumor DNA test was developed to monitor treatment and assess for MRD in patients who have previously been diagnosed with cancer. Available for use in the clinical and research settings, the Signatera MRD test is both personalized and tumor-informed; specifically, it provides a customized blood test that is tailored to fit the specific signature of clonal mutations that are found in that individual’s tumor. The personalized approach increases accuracy with regard to detecting whether residual disease is present or absent from a blood sample.

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With the breakthrough device designation granted in 2019, the Signatera MRD test now has 3 designations for use across several cancer types and indications.

FDA Awards Breakthrough Device Designations to Signatera Molecular Residual Disease Test 

The FDA has granted a fast track designation to poziotinib for use in previously treated patients with HER2 exon 20 mutations, according to an announcement from Spectrum Pharmaceuticals.1 The submission of a new drug application (NDA) for the agent is anticipated later this year, according to Spectrum Pharmaceuticals.

“There are currently no approved therapies to treat patients with HER2 exon 20 mutations and we are pleased that the FDA has granted fast track designation for poziotinib,” Joe Turgeon, president and chief executive officer of Spectrum Pharmaceuticals, stated in a press release. “Momentum is building to unlock the potential of poziotinib.”

 (NCT03318939) were presented at the 2021 ESMO TAT Virtual Congress and showed that when poziotinib was given at a daily dose of 16 mg, it elicited clinically meaningful activity in treatment-naïve patients with metastatic NSCLC with 

 exon 20 mutations.2 The objective response rate (ORR) achieved in this patient population was 27.8% (95% CI, 18.4%-39.1%) and the disease control rate (DCR) was 86.1%.

At a median follow-up of 9.2 months, 12 of 79 patients continued to receive poziotinib. The median duration of response (DOR) with the agent in this cohort was 6.5 months. Notably, 91% of patients in the intent-to-treat (ITT) population experienced tumor shrinkage with poziotinib.

The FDA has granted a fast track designation to poziotinib for use in previously treated non-small cell lung cancer patients with HER2 exon 20 mutations.

FDA Awards Fast Track Status to Treatment for HER2 Exon 20–Mutated NSCLC

The FDA has approved the VENTANA ALK (D5F3) CDx assay as a companion diagnostic to identify patients with 

-positive non–small cell lung cancer (NSCLC) who are eligible to receive treatment with lorlatinib (Lorbrena).1

FDA gave the green light to expand the indication of lorlatinib

 to include use in the frontline treatment of patients with 

-positive NSCLC based on data from the phase 3 CROWN trial (NCT03052608), where the agent led to a 72% reduction in the risk of progression or death vs crizotinib (Xalkori) in treatment-naïve patients (HR, 0.28; 95% CI, 0.19-0.41; 

<.0001) per blinded independent central review assessment.2

Previously, in November 2018, the regulatory agency granted an 

accelerated approval to lorlatinib for use in patients with 

 whose disease had progressed on crizotinib and at least 1 other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor treatment for metastatic disease. The decision was based on a subgroup of 215 patients with 

-positive metastatic NSCLC from Study B7461001 (NCT01970865), in which lorlatinib elicited an overall response rate of 48% (95% CI, 42%-55%).3

“The FDA approval is great news for [patients with] 

-positive [NSCLC],” Jill German, head of Roche Pathology Customer Segment, stated in a press release. “It is essential that we identify patients with this cancer biomarker quickly and accurately so they can be treated with effective targeted therapy. This label expansion advances Roche’s commitment to personalized healthcare by providing [patients with] lung cancer with access to more treatment options and a better chance for progression-free survival compared to standard of care.”

The VENTANA ALK CDx assay is a companion diagnostic to identify patients with ALK-positive non–small cell lung cancer who are eligible to receive treatment with lorlatinib.

FDA Approves Companion Diagnostic for ALK-Positive Non–Small Cell Lung Cancer Treatment 

The FDA has approved axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.1 The regulatory decision was based on data from the phase 2 ZUMA-5 trial (NCT03105336), in which the CAR T-cell product elicited a response in 91% of patients with relapsed/refractory follicular lymphoma (n = 81); this included 60% of patients who achieved a complete remission (CR).

Notably, 74% of patients had a continued remission at 18 months. Among all patients with follicular lymphoma, the median duration of response (DOR) was not yet reached at a median follow-up of 14.5 months.

“Once a follicular lymphoma patient’s disease relapses, the duration of response to care shortens with each round of therapy,” Caron A. Jacobson, MD, MMSc, medical director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, stated in a press release. “Additionally, for patients with follicular lymphoma in the third line of therapy, the 5-year survival rate is only 20%, highlighting the urgent need for treatments that offer a real chance for durable remission. Impressively, 91% of [these] patients in the ZUMA-5 study responded to a single infusion of axicabtagene ciloleucel, including an estimated 74% of patients in a continued remission at 18 months, giving these patients much-needed hope and oncologists an important addition to the treatment armamentarium.”

The single-arm, open-label, multicenter trial enrolled 146 patients with either relapsed or refractory follicular lymphoma and marginal zone lymphoma who had previously received 2 or more lines of systemic therapy, including treatment with an anti-CD20 monoclonal antibody and an alkylating agent.

The FDA has approved axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.

Axi-Cel Granted Accelerated Approval for Relapsed/Refractory Indolent Follicular Lymphoma

The FDA has approved a supplemental new drug application for lorlatinib (Lorbrena) to expand the indication to include the frontline treatment of patients with 

-positive non–small cell lung cancer (NSCLC) as detected by an FDA-approved test. The regulatory based on the data from the pivotal phase 3 CROWN trial (NCT03052608), where lorlatinib resulted in a 72% reduction in risk of progression or death compared with crizotinib (Xalkori) in treatment-naïve patients (HR 0.28; 95% CI, 0.19-0.41; 

<.0001) per blinded independent central review (BICR) assessment.

“For more than a decade, Pfizer has been a pioneer in delivering biomarker-driven therapies and addressing the diverse and evolving needs of people with non-small cell lung cancer,” Andy Schmeltz, Global President of Pfizer Oncology, stated in a press release. “[Lorlatinib] has been a transformative medicine for people with 

-positive advanced NSCLC, and this FDA approval in the first-line setting means that we can now extend hope to even more people.”

Central nervous system (CNS) involvement was evaluated in all study participants. Seventeen patients in the investigative arm and 13 in the control arm had measurable brain metastases per baseline brain imaging. Results from a prespecified exploratory analysis demonstrated that among these patients, the intracranial objective response rate per BICR assessment was 82% (95% CI, 57-96) in the lorlatinib arm vs 23% (95% CI, 5-54) in the crizotinib arm. Moreover, the intracranial duration of response was 12 months or longer in 79% of those who received lorlatinib (n = 11) vs 0% in those given crizotinib.



The FDA has approved a supplemental new drug application for lorlatinib (Lorbrena) to expand the indication to include the frontline treatment of patients with ALK-positive non–small cell lung cancer.

FDA Expands Indication of Lorlatinib for ALK-Positive Non–Small Cell Lung Cancer

A supplemental new drug application (sNDA) has been submitted to the FDA for ivosidenib tablets (Tibsovo) as a potential therapeutic option for patients with previously treated, 

The application is based on findings from the phase 3 ClarIDHy trial (NCT02989857), which has shown that ivosidenib has resulted in a 63% reduction in the risk of disease progression or death compared with placebo in previously treated patients with 

Specifically, the median progression-free survival (PFS) was 2.7 months with ivosidenib vs 1.4 months with placebo (HR, 0.37; 95% CI, 0.25-0.54; 1-sided 

<.0001). The PFS rate with ivosidenib at 6 months was 32%, while the rate was 22% at 12 months. No participants who received placebo were free of progression at either of those time points. The disease control rates at 6 months and 12 months were 53% and 28%, respectively.

Data from the final overall survival (OS) analysis

 of the trial also showed that ivosidenib resulted in a 21% reduction in the risk of death vs placebo in this population.

 The median OS with ivosidenib was 10.3 months vs 7.5 months with placebo (HR, 0.79; 95% CI, 0.56-1.12; 1-sided 

= .093). At 6 months, the OS rate with ivosidenib was 69% vs 57% with placebo. Notably, the rates were not adjusted for crossover. At 12 months, the OS rates in the investigative and control arms were 43% and 36%, respectively.

“Cholangiocarcinoma is a rare, aggressive cancer with limited effective therapies, and patients are in desperate need of new treatment options — particularly those who experience disease progression after chemotherapy,” Chris Bowden, MD, chief medical officer at Agios, stated in a press release. “We are proud of the work we have done on behalf of these patients and look forward to working closely with the FDA during the review of the first oral therapy targeting an 

mutation for patients with previously-treated 

A supplemental new drug application has been submitted to the FDA for ivosidenib tablets (Tibsovo) as a potential therapeutic option for patients with previously treated, IDH1-mutated cholangiocarcinoma.